Pathophysiology of HEENT PDF

Pathophysiology of the Head and Neck Joshua D Stone, Ph.D. Division of Physician Assistant Studies Medical University of South Carolina Lecture Outline: Oral Cavity • Teeth and supporting structures • Inflammatory and other lesions • Infections • Oral manifestations of systemic disease • Tumors an...

Pathophysiology of the Head and Neck Joshua D Stone, Ph.D. Division of Physician Assistant Studies Medical University of South Carolina Lecture Outline: Oral Cavity • Teeth and supporting structures • Inflammatory and other lesions • Infections • Oral manifestations of systemic disease • Tumors and precancerous lesions Teeth and Supporting Structures • Enamel is calcium hydroxyapatite, a hard, inert, acellular tissue (hardest in body) • Dentin contains cells (odontoblasts) which can produce new dentin • Pulp chamber consists of connective tissue rich in nerves, lymphatics and blood vessels • Periodontal ligaments provide a strong and flexible attachment of tooth (cementum) to alveolar bone • Gingiva is mucosa that covers bony surfaces Teeth and Supporting Structures: Dental Caries • One of the most common diseases, the most common cause of tooth loss before age 35 • Improved oral hygiene and fluoridation of the drinking water has reduced caries risk • “Westernization” of global diet dramatically increases caries incidence • Caused by focal degradation of the tooth structure • Result from demineralization of tooth structure by acids, produced from metabolism of sugars by plaque bacteria • Streptococcus mutans and Lactobacillus most common • Fluoride incorporates into the crystalline structure of enamel calcium hydroxyapatite, forming fluoroapatite, which is resistant to bacterial acids Teeth and Supporting Structures: Gingivitis • Gingiva is the squamous mucosa between and around the teeth • Gingivitis is inflammation of the gingiva and associated soft tissues • Usually caused by accumulation of dental plaque – a “biofilm” of bacteria, saliva, bacterial proteins, and desquamated epithelial cells on/between teeth • With time it becomes mineralized to form a calculus (tartar) • Plaque bacteria metabolize sugar, releasing acids which cause caries • Bacterial proteins and metabolic products promote gingival inflammation • Chronic gingivitis is characterized by gingival erythema, edema, easy bleeding, changes in gingival contour, and altered tooth attachment (deeper “pockets”) • Associated with risk for periodontitis Teeth and Supporting Structures: Periodontitis • Periodontitis is caused by inflammation of the supporting structures of the teeth, including the periodontal ligaments, alveolar bone, and cementum • Results in loss of attachment due to destruction of periodontal ligaments and resorption of alveolar bone • Related to change in oral bacterial flora • Associated with complications of pregnancy, risk of endocarditis, abscess • Associated with certain diseases like HIV/AIDS, diabetes, other immune deficiency states • Associated with increased risk for developing chronic disease including diabetes, heart disease, other systemic disease Teeth and Supporting Structures Caries x-ray Gingivitis ↑ and Periodontitis↓ Tartar, gingivitis and periodontal disease Lecture Outline: Oral Cavity • Teeth and supporting structures • Inflammatory and other lesions • Infections • Oral manifestations of systemic disease • Tumors and precancerous lesions Inflammatory/Other Lesions: Fibrous Proliferative Disorders • Irritation fibroma • Most common nodular oral mass • Primarily occurs in the buccal mucosa along the bite line or at the gingivodental margin • A nodular mass of fibrous tissue, with few inflammatory cells, covered by squamous mucosa • Caused by repeated injury • Tx: complete surgical exicision Inflammatory/Other Lesions: Fibrous Proliferative Disorders • Pyogenic granuloma • A highly vascular lesion (sometimes pedunculated) • Usually on the gingiva of children, young adults, pregnant women (pregnancy tumor) • Typically has an ulcerated surface and red to purple color • Can grow rapidly (causing fear of cancer) • Histologically are highly vascular proliferation of granulation tissue • Can regress into a dense fibrous mass • Tx: complete surgical exicision Inflammatory/Other Lesions: Ulcers • Aphthous ulcers (canker sores) • Single or multiple, shallow, hyperemic ulcerations covered by a thin exudate and rimmed by a narrow zone of erythema • Inflammatory lesion with macrophages causing tissue injury and ulceration of oral mucosa • Cause unknown, cluster in families and associated with inflammatory diseases (celiac disease and inflammatory bowel disease) • More common in the first two decades of life • Painful and often recurrent • Usually resolve spontaneously in 1-2 weeks but may persist for weeks Inflammatory/Other Lesions: Glossitis • Glossitis • Inflammation to the tongue for any reason, including trauma, chemicals, infection, or metabolic causes • Includes changes to the tongue resulting from certain vitamin deficiencies (B vitamins) and iron deficiency • Some presentations with no known cause (migratory glossitis) • May be swelling, color changes, pain, papilla changes, or any combination of these Folate/B12 deficiency “atrophic” glossitis Lecture Outline: Oral Cavity • Teeth and supporting structures • Inflammatory and other lesions • Infections • Oral manifestations of systemic disease • Tumors and precancerous lesions Oral Cavity Infections: Bacterial • The oral mucosa is highly resistant to infection by normal bacterial flora • Many defenses • Normal flora is low virulence • Secretory IgA in saliva (antibody that blocks microbial attachment to mucosal surfaces) • Tonsils and adenoids (lymph nodules – like lymph nodes, site for lymphocyte exposure to oral antigens) • Most bacterial infections related to • Immunodeficiency (e.g., young, old, pregnant, disease) • Disruption of the normal flora (e.g., antibiotics) Oral Cavity Infections: Viral • Herpes simplex virus type 1 (HSV-1) most common herpes infection in and around oral cavity, but HSV-2 may occur (usually genital) • Other related viruses include cytomegalovirus, Epstein-Barr virus (infectious mononucleosis), human herpes virus 4, varicella-zoster virus • Primary infection • Typically occurs in infancy to childhood • Viruses infect at site of exposure and replicate in keratinocytes and epithelial cells (including mucosal epithelium) • Infection results in tissue injury and inflammation (vesicles/bullae, red-rimmed, painful ulcers), positive Tzanck test (acantholytic [separated] keratinocytes, multinucleate giant cells, cytoplasmic inclusions) • Acute (initial) infection may be accompanied by lymphadenopathy, fever, anorexia, and irritability • Within 24 hours of infection, virus enters neuronal termini and is transported to sensory ganglia, continue to replicate and establish latency in ganglia Oral Cavity Infections: Herpesvirus • Recurrent infection • Reactivation from latent infection results in anterograde axonal transport to terminals of affected sensory nerves, replication in epithelial cells forming lesions at site of primary infection • Frequently associated with immunosuppression, e.g., stress, diabetes, concurrent illness • Usually less severe presentation than primary infection Skin Ganglion Oral Cavity Infections: Viral • Other viral infections of the oral cavity, head and neck • Enterovirus (includes Coxackie A and B, Echovirus, other Enterovirus species) Herpangina Koplik spots • For example, herpangina (coxackie), hand-foot-andmouth disease (several enterovirus, usually coxackie) • Rubeola virus • Causes measles (Koplik spots) • All have characteristic presentations Hand-foot-and-mouth disease Oral Cavity Infections: Viral Herpes labialis Hand-Foot-Mouth Herpes esophagitis Herpes stomatitis Oral cytomegalovirus Oral herpes zoster Oral Cavity Infections: Fungal • Superficial (usually) and deep tissue fungal infections • Candida albicans infection, called thrush • Superficial infection of mucosal membranes by yeast, may extend into esophagus (also found on other mucosal membranes, moist skin areas) • In oral cavity it presents with a superficial, curd-like, gray to white inflammatory membrane (a “pseudo-membrane” of yeast in a fibrinosuppurative exudate) • Easily scraped off to reveal an underlying erythematous inflamed base • Risk is increased with immunodeficiency, change in mucosal flora (e.g., after antibiotics) Oral candidiasis (thrush) Oral Cavity Infections: Fungi • Deep tissue fungal infections usually have significant morbidity, predilection for the oral cavity and the head and neck region • Manifested by deep ulcers with or without pseudomembranes, may also involve other tissues of head and neck (or elsewhere) • Includes • • • • • • Histoplasmosis, Blastomycosis Coccidioidomycosis Cryptococcosis Zygomycosis Aspergillosis • Risk higher in immunosuppressed populations Blastomycosis Aspergillosis Histoplasmosis Lecture Outline: Oral Cavity • Teeth and supporting structures • Inflammatory and other lesions • Infections • Oral manifestations of systemic disease • Tumors and precancerous lesions Oral Manifestations of Systemic Disease • Some systemic diseases have oral manifestations • Scarlet fever, B-vitamin deficiency, iron deficiency, celiac disease, Sjögren syndrome associated with tongue changes • Crohn’s disease, celiac disease associated with aphthous ulcers • Measles associated with Koplik’s spots • Infectious mononucleosis, diphtheria, streptococcal pharyngitis associated with pseudomembranous tonsillitis Oral Manifestations of Systemic Disease Scarlet fever strawberry tongue Diphtheria pseudomembranous tonsillitis Oral ulcer in Crohn’s disease Mononucleosis pseudomembranous tonsillitis Koplik’s spots (measles) Atrophic glossitis (B12 deficiency) Lecture Outline: Oral Cavity • Teeth and supporting structures • Inflammatory and other lesions • Infections • Oral manifestations of systemic disease • Tumors and precancerous lesions Tumors and Precancerous Lesions: Leukoplakia • Leukoplakia is a white, thickened mucosal patch or plaque, usually with sharply demarcated borders, that cannot be scraped off • Caused by hyperplasia of the squamous epithelium, occurs prior to dysplastic and neoplastic transformation • Until proved otherwise (histology), all leukoplakias should be considered precancerous because up to 20% progress to carcinoma within 10 years • May also seen in purely inflammatory conditions not associated with malignancy • May be caused by human papillomavirus (HPV) infections Presentations of leukoplakia Tumors and Precancerous Lesions: Erythroplakia • Erythroplakia is a red, velvety plaque on epithelial/mucosal surfaces, may be at surrounding height or slightly depressed • Less common than leukoplakia and higher cancer risk • Histologically shows intense subepithelial inflammation with vascular dilation, giving the reddish clinical appearance • Virtually all (approximately 90%) have superficial erosions with dysplasia, carcinoma in situ, or already developed carcinoma Erythroplakia Tumors and Precancerous Lesions: Cancer • Squamous cell carcinoma is the most common form of head and neck cancers (95%), usually arising in the oral cavity • 50% of oropharyngeal cancers are associated with HPV • May arise anywhere but usually the ventral surface of the tongue, floor of the mouth, lower lip, soft palate, and gingiva • Typically preceded by premalignant lesions (leukoplakia, erythroplakia) • Start as raised, firm, pearly plaques or as irregular, roughened, or verrucous (wart-like) areas of mucosal thickening • As they enlarge, they typically create ulcerated and protruding masses that have irregular and indurated (rolled) borders • 5-year survival rate of early-stage oral cancer is approximately 80%, survival drops to 19% for late-stage disease Cancerous Lesions: Squamous Cell Cancer Lecture Outline: Upper Aerodigestive Tract • Nose • Nasopharynx • Epiglottis and larynx Nose: Inflammatory Lesions • Inflammation of the nasal mucosa results in • • • • Mucosal vasodilation (erythema) Mucous membrane edema (“boggy” congestion) Mucous secretion (rhinorrhea) Mucosal tissue proliferation (polyps) with chronic inflammation (non-allergic) Nose: Inflammatory Lesions • Infectious rhinitis (e.g., common cold) caused by viruses • Adenoviruses, echoviruses, and rhinoviruses • Infection of ciliated mucosal epithelial cells results in inflammation (cilia loss, swelling, erythema, increased local production of mucus and clear-topurulent exudate) • Also known as coryza • Secondary bacterial infection enhances the inflammatory reaction and produces mucopurulent exudate, including increased risk for bacterial sinusitis Acute viral rhinitis Acute viral rhinitis with bacterial superinfection Chronic bacterial rhinitis Nose: Inflammatory Lesions • Allergic rhinitis caused by hypersensitivity (allergy) to allergens • Affects ~20% of the US population (common) • An IgE-mediated immune reaction with early- and late-phase responses (Type I hypersensitivity) • Characterized by marked mucosal edema (“boggy”), erythema, and mucus secretion, eosinophil infiltration “Boggy” mucosa Nose: Inflammatory Lesions • Nasal polyps are focal hyperplastic protrusions of the mucosa • Consist of edematous mucosa with loose stroma and hyperplastic or cystic mucous glands, infiltrated with neutrophils and eosinophils • Frequently related to recurrent non-allergic rhinitis • May be large or small • May obstruct the airway and impair sinus drainage Nose: Inflammatory and Infectious Lesions • Acute bacterial sinusitis • Frequently preceded by acute or chronic viral rhinitis • Usually caused by proliferation of oral cavity bacteria in sinuses (often trapped in sinuses by edema, reducing diameter of sinus ostia) • Characterized by facial pain, nasal mucopurulent exudate • Chronic bacterial sinusitis • May develop from acute sinusitis when there is interference with exudate drainage (e.g., polyps, congestion) • Fungal forms may be very severe (consider immunosuppression) • Kartagener syndrome, caused by defective ciliary action, can result in chronic sinusitis (among other problems) Nasal mucosa with patent ostia Edematous nasal mucosa Lecture Outline: Upper Aerodigestive Tract • Nose • Nasopharynx • Epiglottis and larynx Nasopharynx: Inflammatory and Infectious Lesions • Pharyngitis is inflammation and discomfort of the upper and posterior pharynx • Frequently occurs with upper respiratory infections • Most commonly viral infections (rhinoviruses, echoviruses, adenoviruses, respiratory syncytial viruses, influenza virus) • Bacterial infections (Group A streptococci or other pathogens) • More likely to present with tonsillar exudates than viral infections • Group A streptococcus pharyngitis (“strep throat”) can precipitate autoimmune rheumatic fever or related glomerulosclerosis • Signs: • Acute inflammatory response results in erythema and mucosal edema • May produce mucopurulent to pseudo-membranous pharyngeal or tonsillar exudates • Tonsil and cervical chain lymph node swelling Nasopharynx: Inflammatory and Infectious Lesions • Tonsillitis is the enlargement and erythema of the tonsils (exudate may collect in tonsillar crypts) • Risk of developing peritonsillar abscess Group A streptococcal Diphtheria infection with Infection with tonsillar tonsillar and pharyngeal pseudo-membrane exudate (exudative) Peri-tonsillar abscess with distended tonsillar pillar and deviated uvula Grading tonsil size Lecture Outline: Upper Aerodigestive Tract • Nose • Nasopharynx • Epiglottis and larynx Epiglottitis and Larynx: Inflammation • Epiglottitis is inflammation of the epiglottis, usually due to viral infections, sometimes bacterial • In infancy or childhood, mucosal congestion, exudation, or edema may cause airway obstruction • Laryngoepiglottitis, caused by respiratory syncitial virus, Haemophilus influenzae, or group A streptococci • Laryngotracheobronchitis (croup), in which the inflammatory narrowing of the airway produces inspiratory stridor, “barking” cough (parainfluenza virus) • Laryngitis results when the vocal folds become inflamed, producing edema and/or exudate • Causes include allergy, viral or bacterial infection, trauma, or chemical irritation (e.g., stomach acid, smoke) Epiglottis and Larynx: Inflammation Laryngeal edema Epiglottitis Epiglottitis (thumb print sign) Larynx: Reactive Nodules • Reactive nodules/polyps/granumomas develop on the laryngeal folds in response to chemical irritation (e.g., heavy smoking) or chronic strain (e.g., singers nodules) • Laryngeal folds are covered by squamous epithelium, may develop smooth, rounded, sessile or pedunculated lesions (keratotic, hyperplastic, or dysplastic), usually a few millimeters in size and located on the true vocal folds • Singers nodules are bilateral lesions and polyps and granulomas are usually unilateral • Usually cause progressive hoarseness • Rarely become cancerous Singers nodes Pedunculated polyp Granuloma (reflux) Larynx: Squamous Papillomas • Laryngeal squamous papillomas are benign neoplasms • Usually located on the true vocal folds • Soft, raspberry-like growths (usually < 1 cm) which may be caused by HPV (6, 11), other viruses • Central fibrovascular cores and covered by squamous epithelium, may bleed when ulcerated • Single or multiple, sometimes spontaneously regress • Rarely become cancerous Larynx: Neoplasia • Laryngeal neoplasms range from hyperplasia, dysplasia, carcinoma in situ, to invasive carcinoma • About 95% of laryngeal cancers are squamous cell carcinomas • Usually develops directly on the true vocal folds, but may arise elsewhere in larynx • Carcinoma of the larynx manifests with persistent hoarseness • At presentation, about 60% are confined to the larynx • Risk factors include cigarette smoking and alcohol consumption, Caucasian and African ancestry, HPV infection Lecture Outline: Ears and Neck • Inflammatory lesions • Otosclerosis • Tumors • Cysts • Salivary glands Pathophysiology of the Ears: Inflammatory Lesions • Otitis media (OM) is inflammation of the middle ear, generally caused by an infection • Occurs mostly in infants and children • Typically viral, which produces a serous exudate (serous OM) • Serous OM may also be caused by eustachian tube dysfunction, a non-infectious cause Serous otitis media • When associated with bacterial infection, produces a purulent exudate (purulent OM) • Streptococcus pneumoniae, H. influenzae, and Moraxella catarrhalis • Chronic infection may perforate the eardrum, injure the ossicles or labyrinth, spread into the mastoid spaces, or penetrate into the cranial vault (cerebritis, abscess) • Pseudomonas aeruginosa, Staphylococcus aureus, or Purulent otitis media +/- perforation fungus Pathophysiology of the Ears: Inflammatory Lesions • Otitis externa is an inflammatory process of the external auditory canal • Excessive moisture and trauma are the two most common causes of otitis externa • The external auditory canal is warm, dark and moist, supporting bacterial and fungal growth • The skin is thin and easily traumatized Otitis externa • Generally presents with otalgia (ear discomfort or pain) and otorrhea (discharge into or from the external auditory canal) Otitis externa with otorrhea Pathophysiology of the Ears: Inflammatory Lesions • Cholesteatomas of the middle ear are cystic lesions, formed from keratinizing squamous epithelium or metaplastic mucus-secreting epithelium, and filled with cellular debris • Congenital or acquired (acquired are associated with chronic inflammatory conditions) • May cause erosions into surrounding tissue including ossicles, labyrinth, etc. Lecture Outline: Ears and Neck • Inflammatory lesions • Otosclerosis • Tumors • Cysts • Salivary glands Pathophysiology of the Ears: Otosclerosis • Otosclerosis refers to abnormal bone deposition in the middle ear at the rim of the oval window of the cochlea where the stapes attaches • Usually bilateral • Usually begins in the early decades of life, slowly progressive, may lead to marked conductive hearing loss • Usually familial, following autosomal dominant transmission pattern with variable penetrance Lecture Outline: Ears and Neck • Inflammatory lesions • Otosclerosis • Tumors • Cysts • Salivary glands Pathophysiology of the Ears: Tumors • Basal cell and squamous cell carcinomas of the pinna (external ear) are common • Mostly in older men primarily due to sun exposure (light skin) • Cancers within the ear canal tend to be squamous cell carcinomas • Occur in middle-aged to elderly women and are not associated with sun exposure • A large variety of other epithelial and mesenchymal tumors may arise in the ear (external, middle, internal) Pathophysiology of the Ears: Tumors Squamous cell carcinoma Basal cell carcinoma Adenocystic carcinoma Carcinoid tumor Cholesterol granuloma Lecture Outline: Ears and Neck • Inflammatory lesions • Otosclerosis • Tumors • Cysts • Salivary glands Pathophysiology of the Neck: Cysts • Brachial cleft cyst (cervical lymphoepithelial cyst) • Benign cysts usually appear in young to middle aged adults between the ages of 20 and 40 • Usually appear on the upper lateral aspect of the neck along the sternocleidomastoid muscle • Arise from remnants of the brachial arch (2nd > 3rd) • Well circumscribed, 2 to 5 cm in diameter, with fibrous capsule and epithelial lining, and containing clear, watery to mucinous fluid • Enlarge slowly Brachial cleft cyst Pathophysiology of the Neck: Cysts • Thyroglossal duct cyst • Embryological remnants along thyroid developmental tract may persist, producing cysts • Found on anterior midline of neck, attached to base of tongue (moves up when protruding tongue) • Usually 1 to 4 cm diameter, fibrous capsule, epithelial lining, may also include thyroid remnants, contains fluid • Enlarge slowly Thyroglossal duct cyst Lecture Outline: Ears and Neck • Inflammatory lesions • Otosclerosis • Tumors • Cysts • Salivary glands Pathophysiology of the Neck: Salivary Glands • Xerostomia is defined as a dry mouth resulting from a decrease in saliva production • Causes include: • Sjögren syndrome (also have dry eyes) • Radiation therapy • Many classes of medications: anticholinergic, antidepressant/antipsychotic, diuretic, antihypertensive, sedative, muscle relaxant, analgesic, and antihistamine agents • May be associated with dry mucosa and/or tongue changes such as atrophy of the papillae, fissuring and ulcerations • Complications include increased rates of dental caries, thrush, as well as difficulty in swallowing and speaking Pathophysiology of the Neck: Salivary Glands • Sjögren syndrome is an autoimmune disorder characterized by lymphocytic infiltrates into exocrine glands (type 4 hypersensitivity), particularly affecting the salivary and lacrimal glands • Stimulation causes enlargement and eventual destruction of the salivary and lachrymal glands • Dry mouth, dry eyes • Systemic production of diagnostic autoantibodies Parotid enlargement with Sjögren syndrome Pathophysiology of the Neck: Salivary Glands • Sialadenitis is inflammation of the salivary glands • Traumatic, viral, bacterial, or autoimmune • Mumps is a viral cause of sialadenitis (usually parotid) • Nonspecific bacterial sialadenitis is usually secondary to ductal obstruction produced by stones (sialolithiasis) Sialolithiasis of parotid duct Mumps Pathophysiology of the Neck: Salivary Glands • Mucoceles result from either blockage or rupture of a salivary gland duct, with consequent leakage of mucinous saliva into the surrounding connective tissue stroma • A cyst-like space that is lined by inflammatory granulation tissue or by fibrous connective tissue, filled with mucin Mucocele Pathophysiology of the Neck: Salivary Glands • Salivary glands give rise to more than 30 histologically distinct tumors, not including rare benign and malignant mesenchymal neoplasms Lecture Outline: Eye • Orbit • Eyelids • Conjunctiva • Cornea • Anterior segment • Uvea • Retina • Optic nerve From the text… “The eye provides the only site in which a physician can directly visualize a variety of microcirculatory disturbances ranging from arteriosclerosis to angiogenesis in the clinic. Although there are conditions that are unique to the eye (e.g., cataract and glaucoma), many ocular conditions share similarities with disease processes elsewhere in the body that are modified by the unique structure and function of the eye.” Pathophysiology of the Eye: Orbit • The orbit is closed in all directions except anteriorly so disorders that increase orbital contents push the eye forward: proptosis (exopthalmos) • Proptosis may be axial (directly forward) or positional (e.g., medial, lateral, superior, inferior) • Masses in the cone (behind the globe) causes axial proptosis (i.e., straight out) • Masses to the side of the globe will cause the globe to shift away from the mass, e.g., lacrimal gland enlargement results in inferior-medial positional proptosis • Proptosis may result in corneal ulceration and infection risk because of incomplete protection by lid and tear film distribution across the cornea Pathophysiology of the Eye: Orbit Graves disease (thyroid opthamopathy) causes axial proptosis due to accumulation of extracellular matrix proteins and variable degrees of fibrosis in the rectus muscles. A. A 10-month-old girl presenting with an inferior orbital tumor that proved to be a capillary hemangioma. B. CT of this patient shows an inferior orbital tumor mass that has caused expansion of the bony orbit, suggesting a chronic condition. Pathophysiology of the Eye: Orbit • Infection may spread to the orbit via the sinuses or by direct injury, resulting in acute infection (orbital cellulitis) or abscess • Access point to CNS • Fungal infection occurs mostly in immunosuppressed individuals Orbital cellulitis Lacrimal gland abscess Orbital fungal infection Pathophysiology of the Eye: Orbit • Neoplasms • Most common are vascular (unencapsulated) • Capillary hemangioma (infancychildhood) • Lymphangioma and cavernous hemangioma (adults) Capillary hemangioma • Other primary and secondary (metastatic) neoplasms occur Lymphangioma Lecture Outline: Eye • Orbit • Eyelids • Conjunctiva • Cornea • Anterior segment • Uvea • Retina • Optic nerve Pathophysiology of the Eye: Lids • The eyelids (palpebrae) are composed of skin and palpebral conjunctiva • Covers and protects the eye • Sebaceous glands drain at the lid margin (Meibomian and Zeis glands) • Obstruction leads to acute inflammation and infection, blepharitis (generalized) or hordeolum (focal) • Chronic inflammation leads to a granulomatous response producing a granuloma, or chalazion Hordeolum Blepharitis Chalazion Pathophysiology of the Eye: Lids • Neoplasms • Skin: • Most common is basal cell carcinoma – predilection for lower lid and medial canthus • 3rd most common is squamous cell carcinoma • Invasive tumors can disturb the cornea so need prompt evaluation/removal Basal cell carcinoma • Sebaceous carcinoma • 2nd most common – may form a local mass that mimics a chalazion, or may diffusely thicken the eyelid • Capable of intraepithelial (Pagetoid) spread – usually parotid and submandibular nodes Sebaceous cell carcinoma Squamous cell carcinoma Lecture Outline: Eye • Orbit • Eyelids • Conjunctiva • Cornea • Anterior segment • Uvea • Retina • Optic nerve Pathophysiology of the Eye: Conjunctiva • Conjunctiva is divided into 3 zones • Palpebral conjunctiva - ”folded” response to allergic and bacterial inflammation • Fornix contains accessory lacrimal tissue (dry eye) and lymphoid tissue (enlarges with viral infection, sarcoid) • Bulbar conjunctiva – nonkeratinized epi covering the surface of the sclera • Highly vascular (blood and lymphatic vessels) • Hemorrhage affects the conjunctiva but not the cornea • Neoplasms tend to spread to draining lymph node chains Subconjunctival hemorrhage Pathophysiology of the Eye: Conjunctiva • Conjunctivitis → injection and prominence of conjunctival vessels • Many causes: • • • • Chemicals Allergy Viral infection Bacterial infection Chemical conjunctivitis Allergic conjunctivitis • Most pain free with no visual anomaly heal spontaneously without sequelae Viral conjunctivitis Bacterial conjunctivitis Pathophysiology of the Eye: Conjunctiva • Some infections, injuries, other disorders may produce conjunctival scarring • Results in tissue contraction → distortion of the fornices and/or lids → reduced # goblet cells → reduced mucin → reduced tear adherence (dry eye) • May cause entropion or extropion Chlamydia trachomatis (trachoma) with upper/lower entropion • Many causes: • Persistent bacterial or viral conjunctivitis • • • • • Chlamydia trachomatis (trachoma) Alkali exposure Ocular Cicatricial Pemphigoid (autoimmune/genomic) Surgical or traumatic injury Drugs Ocular pemphigoid Pathophysiology of the Eye: Conjunctiva • Sun damage (“actinic”) causes submucosal conjunctival hyperplasia and tissue elevation • Pterygium • Formed by a wedge shaped, submucosal growth of fibrovascular connective tissue that migrates onto the cornea • Can result in an uneven distribution of the tear film over the cornea (resulting in dry eyes) • Can invade the cornea but does not cross the pupillary axis (may cause mile astigmatism) • Usually benign, but rarely precursor to squamous cell carcinoma Pterygium • Pinguecula • Small, clear to yellowish submucosal elevation containing fat, proteins and other materials • Does not invade the cornea but can result in an uneven distribution of the tear film over the cornea Pinguecula Pathophysiology of the Eye: Conjunctiva • Conjunctival neoplasms tend to develop at the limbus (edge of iris) • Squamous cell carcinoma • Melanoma • Mucoepidermoid carcinoma • Conjunctival nevi Conjunctival melanoma • Risk for melanoma Squamous cell carcinoma Conjunctival nevus Lecture Outline: Eye • Orbit • Eyelids • Conjunctiva • Cornea • Anterior segment • Uvea • Retina • Optic nerve Pathophysiology of the Eye: Cornea • Corneal tissue is avascular with a thin outer layer of corneal epithelial cells (neuronal) on a basement (Descemet) membrane • Major refractive surface (injury always affects visual acuity) • Clarity related to lack of blood/lymphatic vessels and to collagen fiber alignment • Minimal changes in shape and transparency affect visual acuity (e.g., scarring, edema, angiogenesis) Pathophysiology of the Eye: Cornea • Keratitis results from injury to the corneal epithelium (and underlying tissue), resulting in inflammation • Causes include bacterial, viral, fungal and protozoal infection, trauma (e.g., welding) • Inflammatory response to infection → purulent exudates in anterior chamber (hypopyon) and/or ciliary injection → dissolution of corneal stroma by activation of collagenases → granulomatous ulceration in DM (HSV) • May cause long-term visual acuity changes if corneal changes are permanent (tissue death, scarring) Acanthamoeba keratitis with hypopyon Corneal ulcer (fluorescein stain) Lecture Outline • Orbit • Eyelids • Conjunctiva • Cornea • Anterior segment • Uvea • Retina • Optic nerve Pathophysiology of the Eye: Anterior Segment • Anterior segment • The anterior segment (chamber) is bounded anteriorly by the cornea, laterally by the trabecular meshwork, and posteriorly by the iris • Aqueous humor from the ciliary body (posterior to the iris) travels between the lens and iris, circulates through the pupil to gain access to the anterior chamber, and is reabsorbed by the trabecular meshwork • The lens is an epithelial tissue fully encapsulated by basement membrane therefore does not exfoliate but does infoliate with age (i.e., changes are permanent) Pathophysiology of the Eye: Anterior Segment • Hyphemia is bleeding into the anterior chamber caused by trauma, inflammatory or infectious disorders • Hypopyon is a collection of pus in the anterior chamber associated with inflammatory or infectious disorders Hyphemia Hypopyon Pathophysiology of the Eye: Anterior Segment • Cataracts are congenital or acquired opacities of the lens caused by deposits of pigment or oxidized / modified proteins, causing loss of transparency • Associated with • Systemic / metabolic diseases • Diabetes mellitus, galactosemia, Wilson disease, atopic dermatitis • Drugs • Corticosteroids • Other • Radiation, sun exposure, trauma, intraocular disorders Senile cataract Pathophysiology of the Eye: Anterior Segment • Glaucoma refers to diseases characterized by visual field changes and are usually associated with elevated intra-ocular pressure • Two primary types: • Open-angle glaucoma → aqueous humor has access to the trabecular meshwork but it is not reabsorbed at a sufficient rate to prevent pressure elevation • Closed-angle glaucoma → the peripheral zone of the iris adheres to the trabecular meshwork and physically impedes reabsorption of aqueous humor • Persistently elevated intraocular pressure damages optic nerve, results in optic disk “cupping” • Some individuals with normal intra-ocular pressure may develop characteristic optic nerve and visual field changes (normal or low-tension glaucoma) Lecture Outline • Orbit • Eyelids • Conjunctiva • Cornea • Anterior segment • Uvea • Retina • Optic nerve Pathophysiology of the Eye: Uvea • Uvea • Composed of the iris, ciliary body, and the choroid • Uveitis • Inflammation of any tissue of the uvea • Uveitis may be related to other inflammatory disorders (Reiter syndrome, sarcoidosis, inflammatory bowel disease, psoriasis) or infections (Lyme disease, toxoplasmosis, syphilis, herpes simplex, herpes zoster and tuberculosis) • Uveitis can cause glaucoma • Frequently results in ciliary injection Iritis • Iritis is inflammation of the iris (results in uneven iris) Uveitis (with hypopyon) Pathophysiology of the Eye: Uvea • Neoplasm of the uvea occurs typically in the choroid (i.e., posterior chamber) • Uveal melanoma is the most common primary intra-ocular malignancy of adults • Incidence increases with age • Etiology unclear Uveal melanoma • Uveal nevi are common, affecting an estimated 10% of the Caucasian population • Progression to melanoma is very uncommon Uveal nevus Lecture Outline • Orbit • Eyelids • Conjunctiva • Cornea • Anterior segment • Uvea • Retina • Optic nerve Pathophysiology of the Eye: Retina • The retina is an embryologic derivative of the brain • Pathology may develop by • • • • • Retinal detachment (separation) Hemorrhage and other vascular disease Age-related and hereditary degeneration Inflammation Neoplasia Pathophysiology of the Eye: Retina • Retinal detachment occurs when there is a separation of the retina from the deeper retinal pigmented epithelium (RPE) • Retinal detachment without retinal tear (non-rhegmatogenous) • Associated with any condition that damages the RPE and permits fluid to leak under the retina (e.g., choroidal tumors and malignant hypertension) • Retinal detachment with a full-thickness retinal tear (rhegmatogenous) • Occurs after the vitreous collapse / detachment Pathophysiology of the Eye: Retina Retinal detachment (non-rhegmatogenous) See https://litfl.com/acurtain-descends/ for ultrasound examination Retinal tear (rhegmatogenous) Pathophysiology of the Eye: Retina • Retinal vascular disease • Hypertension promotes retinal arteriosclerosis (“copper” wire) while also compressing veins (AV nicking) • Both compromise blood supply and increased venous pressure • Occlusion leads to nerve infarcts, forming “cotton-wool spots” • Hemorrhage occurs when a vessel breaks or leaks • Flame (surface) and dot (deep) hemorrhages • Exudates (protein, pigment deposits) accumulate with repeated edema • Proliferative retinopathy • Caused by retinal angiogenesis (diabetes mellitus) • Arterial and venous occlusion, leading to nerve infarct • Thrombotic (occurs there) or embolic (travels from elsewhere) Pathophysiology of the Eye: Retina Retinal detachment Hypertensive retinal changes (retinopathy): AV nicking, arteriolar narrowing, cotton-wool spots, hemorrhages, copper wiring, opic disk swelling Proliferative retinopathy with hemorrhages Pathophysiology of the Eye: Retina • Macular degeneration • Loss of central vision due to injury and death of rods and conesin the macula • Mostly heritable, associated with aging • Dry form • Characterized by yellow “drusen” exudate deposits of proteins and lipids in the macula (yellow in fundal pictures), between RPE and choroid Wet • Wet form • Characterized by proliferative neovascularization of the macula • Blood and fluid leaking over the macula eventually causes pigment deposition, scarring Dry Pathophysiology of the Eye: Retina • Retinal degeneration • Retinitis pigmentosa • Fairly common inherited retinal disorders (1/3600 incidence) • X-linked recessive, autosomal recessive, or autosomal dominant (the age of onset correlates with the inheritance pattern) • Linked to mutations in genes that regulate the functions of either the photoreceptor cells (rods and cones) or the RPE • The mutations cause both rods and cones to die by apoptosis • Loss of rods leads to early night blindness and constricted visual fields • As cones are lost, central visual acuity is lost • Black pigment deposit (“bone spicule pigmentation”) is pathognomonic • Virtually always bilateral Pathophysiology of the Eye: Retina • Inflammatory disorders: Infectious retinitis • A variety of pathogens can contribute to the development of infectious retinitis • Hematogenous dissemination of pathogens to the retina may result in retinal abscesses or other infections, particularly in immunocompromised patients Pathophysiology of the Eye: Retina • Neoplasia • Retinoblastoma • • • • The most common primary intra-ocular malignancy of children Neuronal origin, hereditary association in 40% of cases Loss of red reflex (leukocoria) 2/3 are unilateral • Retinal lymphoma • Primary intra-ocular lymphoma usually occurs in older individuals and may mimic uveitis • Fundoscopy demonstrates typical “leopard fur” appearance • Diagnosis depends on a demonstration of lymphoma cells in vitreous aspirates Retinal Neoplasms Retinoblastoma viewed with fundoscopy Leukocoria, loss of the red reflex of the eye, in children with retinoblastoma https://www.aafp.org/afp/2006/0315/p1039.html Retinal lymphoma showing the typical “Leopard Fur” appearance, due to infiltration under the retinal pigmented epithelium, causing retinal pigment epithelium clumping and atrophy Lecture Outline • Orbit • Eyelids • Conjunctiva • Cornea • Anterior segment • Uvea • Retina • Optic nerve Pathophysiology of the Eye: Optic Nerve • Papilledema • Edema of the head of the optic nerve may develop as a consequence of compression of the nerve (primary neoplasm of the optic nerve, nerve inflammation - neuritis) or from elevations of CSF pressure surrounding the nerve Normal fundus • Causes venous stasis, leading to nerve head edema • When due to increased intracranial pressure usually bilateral Papilledema Pathophysiology of the Eye: Optic Nerve • Optic neuropathy • Damage to optic nerves from any cause • Results in reduced / modified or lost vision • Causes include: • Glaucoma causes compression of the optic nerve, eventually resulting in death of nerve fibers • Inherited (e.g., Leber hereditary optic neuropathy) • Secondary to nutritional deficiencies (thiamine, B12) or toxins such as methanol • Ischemia, infarct Pathophysiology of the Eye: Optic Nerve • Anterior ischemic optic neuropathy (AION) • A spectrum of injuries to the optic nerve varying from ischemia to infarction (CVA) • Episodes of transient to permanent loss of vision, either segmental or total • The optic nerve does not regenerate, and visual loss from infarction is permanent • Optic nerve inflammation results in papilledema Normal fundus • Causes include • Arteritic AION, caused by interruption in the blood supply to the optic nerve due to arterial stenosis from arteriosclerosis or arteritis • Non-arteritic AION, because of embolic or thrombotic ischemia AION (resulting from giant cell arteritis) Pathophysiology of the Eye: Optic Nerve • Optic neuritis • Describes the loss of vision secondary to inflammation of the optic nerve, often associated with demyelinization • Causes include • Autoimmune: Multiple sclerosis, Lupus, autoimmune vasculitis • Bacterial infections: Lyme disease, tuberculosis, cat scratch fever, toxoplasmosis and syphilis • Viral infections: HIV, hepatitis B, and herpes zoster • Diabetes: Ischemia and hyperglycemia • Drugs: Ethambutol and certain antibiotics • NOTE: Toxins like lead, methyl alcohol, quinine, and arsenic may cause vision loss and other symptoms that may mimic optic neuritis