Pathophysiology of Common

Diseases of Upper Respiratory

Tract
By: Dr. Milkias (Pathology Resident)

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 Common Cold(Infectious Rhinitis)

• A viral illness in which the symptoms of rhinorrhea and

nasal obstruction are prominent; systemic symptoms
and signs such as myalgia and fever are absent or mild.
• It is often termed rhinitis but includes self-limited
involvement of the sinus mucosa and is more correctly
termed rhinosinusitis.
• ETIOLOGY.
• The most common pathogens associated with the
common cold are the rhinoviruses, but the syndrome
can be caused by many different viruses
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 ETIOLOGY.

• The most common pathogens are the rhinoviruses but the

syndrome can be caused by many different viruses.
• Other causes
– Respiratory syncytial viruses
– Human metapneumovirus
– Influenza viruses
– Parainfluenza viruses
– Adenoviruses
– Enteroviruses
– Bocavirus
-Coronaviruses
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 Epidemiology
• Colds occur year-round, but the incidence is
greatest from the early fall until the late spring
• Incidence in Young children is on an average 6–8
colds per year but 10–15% of children have at
least 12 infections per year.
• Adults have 2-3 illness per yr.
• Children in daycare centers during the 1st year of
life have 50% more colds than children cared at
home.
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 Pathophysiology
• During the initial acute stages, the nasal
mucosa is thickened, edematous, and red
• the nasal cavities are narrowed; and the
turbinates are enlarged.
• These changes may extend, to produce
pharyngotonsillitis.
• Secondary bacterial infections also occur

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 Clinical Features
• sore or “scratchy” throat,
• nasal obstruction and rhinorrhea.
• Cough is associated with ≈30% of colds and
usually begins after the onset of nasal
symptoms.
• The usual cold persists for about 1 wk,
although 10% last for 2 wk.

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 Diagnosis
• Common cold is diagnosed clinically
• differentials
Allergic rhinitis Prominent itching and sneezing
  Nasal eosinophils
Foreign body Unilateral, foul-smelling secretions

  Bloody nasal secretions

Sinusitis Presence of fever, headache or facial pain,
or periorbital edema or persistence of
rhinorrhea or cough for >14 days

Streptococcosis Nasal discharge that excoriates the nares

Pertussis Onset of persistent or severe cough

Congenital syphilis Persistent rhinorrhea with onset in the 1st 3

mo of life
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 Complications
• Otitis media
• Sinusitis
• Exacerbation of bronchial asthma
• Pneumonia
• Diarrhea

 Treatment : Supportive care

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 Allergic Rhinitis
• Allergic rhinitis (hay fever) is initiated by hypersensitivity
reactions to one of a large group of allergens, most
commonly the plant pollens, fungi, animal allergens, and
dust mites.
• As is the case with asthma, allergic rhinitis is an IgE­
mediated immune reaction with an early­and late phase
response (Type I Hyper sensitivity”).
• The allergic reaction is characterized by marked mucosal
edema, redness, and mucus secretion, accompanied by a
leukocytic infiltration in which eosinophils are prominent

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 Chronic Rhinitis
• Chronic rhinitis is a squeal to repeated attacks
of acute rhinitis, either microbial or allergic in
origin, with the eventual development of
superimposed bacterial infection

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 Nasal Polyps
• Recurrent attacks of rhinitis may eventually lead to
focal protrusions of the mucosa, producing so­called
nasal polyps, which may reach 3 to 4 cm in length.
• On histologic examination these polyps consist of
edematous mucosa having a loose stroma, often
harboring hyperplastic or cystic mucous glands,
infiltrated with a variety of inflammatory cells,
including neutrophils, eosinophils, and plasma cells
with occasional clusters of lymphocytes

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 Sinusitis
• Acute sinusitis is most commonly preceded by acute
or chronic rhinitis, but maxillary sinusitis
occasionally arises by extension of a periapical
infection through the bony floor of the sinus. The
offending agents are usually inhabitants of the oral
cavity, and the inflammatory reaction is entirely
nonspecific
• Acute sinusitis may, in time, give rise to chronic
sinusitis, particularly when there is interference with
drainage.
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 Cont’d…
• Differentiating bacterial sinusitis from a cold may be
difficult, but certain patterns suggestive of sinusitis have
been identified.
• These include persistence of nasal congestion,
rhinorrhea (of any quality) and daytime cough ≥10 days
without improvement; severe symptoms of temperature
≥39°C (102°F) with purulent nasal discharge for 3 days or
longer; and worsening symptoms either by recurrence of
symptoms after an initial improvement or new
symptoms of fever, nasal discharge and daytime cough.

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 Cont’d…
• the infections have the potential of spreading into
the orbit or of penetrating into the surrounding
bone to give rise to osteomyelitis or spreading into
the cranial vault, causing septic thrombophlebitis of
a dural venous sinus, brain abscess and meningitis.
• Rx: Initial therapy with amoxicillin (50 mg/kg/day
divided bid) is adequate for the majority of children
with uncomplicated mild to moderate severity acute
bacterial sinusitis

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 Necrotizing Lesions of the Nose and
Upper Airways
• Acute fungal infections (including
mucormycosis; particularly in patients with
diabetes and immunosuppressed patients
• Granulomatosis with polyangiitis, previously
called Wegener granulomatosis
• Extranodal NK/T ­cell lymphoma, nasal type, is
a lymphoma in which the tumor cells harbor
EBV.

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 Tonsillopharyngitis/pharyngotonsillitis.

• Pharyngitis and tonsillitis are frequent features of viral

upper respiratory infections.
• Most commonly implicated are the rhinoviruses,
echoviruses, and adenoviruses, and, less frequently,
respiratory syncytial viruses and the various strains of
influenza virus.
• In the usual case, there is reddening and edema of the
nasopharyngeal mucosa, with reactive enlargement of
nearby tonsils and lymph nodes.
• Bacterial infections may be superimposed on these viral
infections, or may be primary invaders.
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• The most common offenders are the β­
hemolytic streptococci, but sometimes
Staphylococcus aureus or other pathogens
may be implicated.
• The inflamed nasopharyngeal mucosa may be
covered by an exudative membrane
(pseudomembrane), and the nasopalatine and
palatine tonsils may be enlarged and covered
by exudate
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 EPIDEMIOLOGY.

• Viral upper respiratory tract infections are spread by

close contact and occur most commonly in fall, winter,
and spring.
• Streptococcal pharyngitis is uncommon before 2–3 yr
of age, has a peak incidence in the early school years,
and declines in late adolescence and adulthood.
• Illness occurs most often in winter and spring and
spreads among siblings and classmates.
• Primary infection with HIV also manifests with
pharyngitis and a mononucleosis-like syndrome.
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 PATHOGENESIS OF GABHS.

• Colonization of the pharynx by GABHS can result in either

asymptomatic carriage or acute infection.
• The M protein is the major virulence factor of GABHS and
facilitates resistance to phagocytosis by polymorphonuclear
neutrophils.
• Scarlet fever is caused by GABHS that produces 1 of 3
streptococcal erythrogenic exotoxins (A, B, and C) that can induce
a fine papular rash.
• Exotoxin A appears to be most strongly associated with scarlet
fever.
• Exposure to each exotoxin confers specific immunity only to that
toxin and, therefore, scarlet fever can occur up to 3 times.

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• The major importance of streptococcal “sore
throats” lies in the possible development of
late sequelae, such as acute rheumatic fever,
glomerulonephritis and chronic tonsillar
enlargement .

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 Clinical Features
• Incubation period is 2–5 days, rapid onset
• Symptoms
– sore throat, absence of cough, and fever.
– Headache , abdominal pain, vomiting .
• Physical exam
– Pharynx is red, and tonsils are enlarged and covered with a yellow, blood-
tinged exudate.
– There may be petechiae or “doughnut” lesions on the soft palate and
posterior pharynx, and the uvula may be red, stippled, and swollen.
– Enlarged and tender anterior cervical lymph nodes.
– Stigmata of scarlet fever: circumoral pallor, strawberry tongue, and a red,
finely papular rash that feels like sandpaper and resembles sunburn with
goose pimples.

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 Diagnosis
• Throat swab culture
• Rapid antibody tests
 Treatment
• Most untreated episodes of streptococcal pharyngitis
resolve uneventfully in a few days, but early antibiotic
therapy hastens clinical recovery by 12–24 hr.
• The primary benefit of treatment is the prevention of
acute rheumatic fever, which is almost completely
successful if antibiotic treatment is instituted within 9
days of illness.
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 Acute Epiglottitis (Supraglottitis)
• This now rare, but still dramatic and potentially
lethal condition is characterized by an acute
rapidly progressive and potentially fulminating
course of high fever, sore throat, dyspnea, and
rapidly progressing respiratory obstruction.
• Sudden onset of sore throat and fever
followed within a matter of hours as toxic,
swallowing difficulty, and labored breathing.

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• Drooling of saliva and hyperextended neck,
assume the tripod position, sitting upright and
leaning forward with the chin up and mouth
open while bracing on the arms.
• The barking cough typical of croup is rare.

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 Etiologies
• Haemophilus influenzae type b.
• Streptococcus pyogenes,
• Streptococcus pneumoniae,
• Staphylococcus aureus,
• In the prevaccine era, the typical patient with
epiglottitis due to H. influenza type b was 2–4
yr of age.

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 Diagnosis
• The diagnosis requires visualization under
controlled circumstances of a large, cherry red,
swollen epiglottis by laryngoscopy
• If epiglottitis is thought to be possible but not
certain in a patient with acute upper airway
obstruction, the patient may undergo lateral
radiographs of the upper airway first.
• Classic radiographs of a child who has
epiglottitis show the thumb sign
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 Treatment
• Artificial airway
• Oxygen
• Ceftriaxone, cefotaxime, or a combination of
ampicillin and sulbactam
• Racemic epinephrine and corticosteroids are
ineffective.
• Antibiotics should be continued for 7–10 days.

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 Croup(Laryngotracheobronchitis)
• The term croup refers to a heterogeneous group of mainly
acute and infectious processes that are characterized by a
barklike or brassy cough and may be associated with
hoarseness, inspiratory stridor, and respiratory distress.
• Croup typically affects the larynx, trachea, and bronchi.
• Inflammation involving the vocal cords and structures
inferior to the cords is called laryngitis, laryngotracheitis,
or laryngotracheobronchitis, and inflammation of the
structures superior to the cords is called supraglottitis

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 Croup Syndrome

• Croup describes acute inflammatory diseases

of the larynx, including viral croup
(laryngotracheobronchitis), epiglottitis
(supraglottitis), and bacterial tracheitis.

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 ETIOLOGY AND EPIDEMIOLOGY
• Causes of viral croup
– parainfluenza viruses account for ≈75% of cases; other viruses associated with this
disease include
– influenza A and B, Influenza A has been associated with severe laryngotra cheobronchitis.
– adenovirus,
– respiratory syncytial virus (RSV), and
– measles.
• Most patients with croup are between the ages of 3 mo and 5 yr, with the peak
in the 2nd yr of life.
• The incidence of croup is higher in males; it occurs most commonly in the late
fall and winter but may occur throughout the year.
• Recurrences are frequent from 3–6 yr of age and decrease with growth of the
airway.
• Approximately 15% of patients have a strong family history of croup.

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 Clinical features
• Rhinorrhea, pharyngitis, mild cough, and low-grade fever
• “barking” cough, hoarseness, and inspiratory stridor
• Symptoms are worse at night and often recur with decreasing
intensity for several days and resolve completely within a wk.
• Agitation and crying greatly aggravate the symptoms and
signs.
• hoarseness voice, coryza, normal to moderately inflamed
pharynx, and a slightly increased respiratory rate.
• Patients vary substantially in their degree of respiratory
distress

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 Diagnosis
• Croup is a clinical diagnosis and does not
require a radiograph of the neck.
• Radiographs of the neck can show the typical
subglottic narrowing, or steeple sign, of croup
on the posteroanterior view

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 Westley Croup score,components
• Level of consciousness: Normal, including sleep
= 0; disoriented = 5
• Cyanosis: None = 0; with agitation = 4; at rest = 5
• Stridor: None = 0; with agitation = 1; at rest = 2
• Air entry: Normal = 0; decreased = 1; markedly
decreased = 2
• Retractions: None = 0; mild = 1; moderate = 2;
severe = 3

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 Westley Croup score
 • Mild croup
croup score of ≤2.
barking cough, hoarse cry, but no stridor at rest.
 • Moderate croup
croup score of 3 to 7.
stridor at rest, at least mild retractions, and other symptoms or signs of respiratory
distress, but little or no agitation.
 • Severe croup
croup score of ≥8.
significant stridor at rest, although stridor may decrease with worsening upper
airway obstruction
decreased air entry.
severe retractions and the child may appear
anxious, agitated, or fatigued.

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 Diagnosis and treatment
• The mainstay of treatment for children with croup is
airway management and treatment of hypoxia
• Mild &Moderate croup
– Dexamethasone 0.6 mg/kg im stat , watch for discharge if
improvement noted , mist therapy at home.
• Severe croup
– Admit
– Racemic epinephrine/ l-epinephrine + dexamethasone + cool
mist therapy.
– Tracheostomy if impending respiratory failure despite medical
treatment.

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 Acute Infectious Laryngitis
• Laryngitis is a common illness. Viruses cause most cases; diphtheria is an
exception.
• The onset is usually characterized by an upper respiratory tract infection
during which sore throat, cough, and hoarseness appear.
• The illness is generally mild; respiratory distress is unusual except in the
young infant.
• Hoarseness and loss of voice may be out of proportion to systemic signs
and symptoms.
• The physical examination is usually not remarkable except for evidence
of pharyngeal inflammation.
• Inflammatory edema of the vocal cords and subglottic tissue may be
demonstrated laryngoscopically.
• The principal site of obstruction is usually the subglottic area.

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 Otitis Media
• Otitis media is the second most common disease of
childhood, after upper respiratory infection.
• The peak incidence and prevalence is from 6–20 mo of
age.
• Important in the differential diagnosis of fever
• Propensity to become chronic and recur.
• The earlier in life a child experiences the 1st episode, the
greater the degree of subsequent difficulty he or she is
likely to experience, in terms of frequency of recurrence,
severity, and persistence of middle-ear effusion.

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 Etiology
• S. pneumoniae in 40% of cases
• nontypable Haemophilus influenzae in 25–
30%
• Moraxella catarrhalis in 10–15%.
• group A streptococcus, Staphylococcus
aureus, and gram-negative organisms
together in 5% of cases.

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 Pathophysiology
• The most important factor in middle ear disease is eustachian
tube (ET) dysfunction.
• In ET dysfunction (ETD), the mucosa at the pharyngeal end of
the ET is part of the mucociliary system of the middle ear.
Interference with this mucosa by edema, tumor, or negative
intratympanic pressure facilitates direct extension of infectious
processes from the nasopharynx to the middle ear, causing OM.
• Esophageal contents regurgitated into the nasopharynx and
middle ear through the ET can create a direct mechanical
disturbance of the middle ear mucosa and cause middle ear
inflammation.

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 Why children develop recurrent AOM

• Developmental alterations of the ET( ET is

horizontal and in direct communication with
the pharynx)
• Immature immune system
• Frequent infections of the upper respiratory
mucosa

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• More than one third of children experience 6 or
more episodes of AOM by age 7 years.
• Otitis media with effusion (OME), formerly termed
serous OM or secretory OM, is MEE of any duration
that lacks the associated signs and symptoms of
infection (eg, fever, otalgia, irritability). OME
usually follows an episode of AOM.
• Chronic suppurative OM is a chronic inflammation
of the middle ear that persists at least 6 weeks and
is associated with otorrhea through a perforated
TM.
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 Clinical features
• Acute OM (AOM) implies • abnormal otoscopic
rapid onset of disease findings of the tympanic
associated with 1 or more of
membrane (TM:
the following symptoms:
• Otalgia • Opacity
• Fever • Bulging
• Otorrhea • Erythema
• Recent onset of anorexia • Middle ear effusion
• Irritability (MEE)
• Vomiting
• Diarrhea

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 Diagnosis

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 Treatment
• For younger patients, <2 yr of age, treat all
confirmed diagnoses of AOM.
• In very young patients, <6 mo of age, even
presumed episodes of AOM should be treated
due to the increased potential of significant
morbidity from infectious complications
• Choice of antibiotics are penicillins.

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 Complications
Intratemporal complications  Intracranial complications
– Hearing loss (conductive and – Meningitis 
sensorineural)  – Subdural empyema 
– TM perforation (acute and chronic)  – Brain abscess 
– Chronic suppurative OM (with or – Extradural abscess 
without cholesteatoma)  – Lateral sinus thrombosis 
– Cholesteatoma 
– Otitic hydrocephalus
– Tympanosclerosis 
– Mastoiditis 
– Petrositis 
– Labyrinthitis
– Facial paralysis 
– Cholesterol granuloma 
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 Nasopharyngeal Carcinoma
• Squamous cell carcinoma of the nasopharynx is a leading
cause of death for large populations in Southeast Asia and,
to less degree, in northern Africa.
• The age–incidence curve is bimodal, with a peak occurring
between 15 and 25 years and another between 60 and 69
years.
• This tumor results from the combined action of genetic
predisposition, environmental factors, and the EBV.
• The association with EBV is much stronger in endemic
areas (such as Southeast Asia) than in other parts of the
world.
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 Cont’d…
• Three factors influence the origins of these neoplasms: (1)
heredity, (2) age, and (3) infection with EBV
• Nasopharyngeal carcinomas are particularly common in
some parts of Africa, where they are the most frequent
childhood cancer.
• In contrast, in southern China, they are very common in
adults but rarely occur in children.
• In addition to EBV infection, diets high in nitrosamines,
such as fermented foods and salted fish, as well as other
environmental insults such as smoking and chemical fumes,
have been linked to the disease.
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 Microscopic Features
• Microscopically, the crucial distinction to be
made in nasopharyngeal carcinoma is between
tumors that show clear-cut evidence of
keratinization and those that do not
• NPC takes one of three patterns: (1) keratinizing
squamous cell carcinomas, (2) nonkeratinizing
squamous cell carcinomas, and (3)
undifferentiated/basaloid carcinomas that have
an abundant non­neoplastic, lymphocytic infiltrate

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 Clinical presentation
• Primary nasopharyngeal carcinomas are often
clinically occult for long periods, and present
with nasal obstruction, epistaxis, and often
metastases to the cervical lymph nodes in as
many as 70% of the patients.

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 Treatment
• For all types, there is an overall 5­year survival
of approximately 60%. Depending on stage,
the 5­year survival for the nonkeratinizing type
is 70% to 98%, while the 5­year survival for the
keratinizing form is approximately 20%.
• Radiotherapy is the standard treatment

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 Laryngeal Tumors
 Laryngeal Squamous Papilloma and Papillomatosis
• are benign neoplasms, usually located on the true
vocal cords, that form soft, raspberry-like
proliferations rarely more than 1 cm in diameter.
• On histologic examination, the papillomas are made
up of multiple slender, finger­like projections
supported by central fibrovascular cores and
covered by an orderly stratified squamous
epithelium.

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 Cont’d…
• Papillomas are usually single in adults but are often
multiple in children, in whom they are referred to as
juvenile laryngeal papillomatosis. However, multiple
recurring papillomas also occur in adults.
• The lesions are caused by HPV types 6 and 11.
• They do not become malignant, but frequently
recur. They often spontaneously regress at puberty,
but some affected patients endure numerous
surgeries before this occurs.

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 Carcinoma of the Larynx

• Carcinoma of the larynx is typically a squamous cell

carcinoma seen in male chronic smokers.
• They range from hyperplasia, atypical hyperplasia,
dysplasia, and carcinoma in situ to invasive
carcinoma(Sequence of Hyperplasia-Dysplasia-
Carcinoma)
• Smoking and alcohol increase the risk substantially.
• Other factors that may contribute to increased risk
include nutritional factors, exposure to asbestos,
irradiation, and infection with HPV.
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• Carcinoma of the larynx is most commonly seen
in men in the sixth decade of life and often
manifests clinically as persistent hoarseness,
dysphagia, and dysphonia. Prognosis is highly
dependent on clinical staging.
• Combined chemotherapy and radiation therapy,
with or without salvage laryngectomy, may be
required for more advanced or recurrent disease

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 Vocal Cord Nodule
• Vocal cord (laryngeal) nodule represents a
peculiar noninflammatory reaction to injury
causing hoarseness, which is seen more
commonly in people who misuse their voices
• It occurs chiefly on the anterior third of the
vocal cords and has also been called singer’s
nodule, amyloid tumor, vocal cord polyp, and
varix

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 THANK YOU

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