1. The Upper Respiratory System
Nose
Pharynx (throat)
Middle ear
Eustachian tubes

2. Structures of Upper Respiratory System
Figure 24.1

3. The Lower Respiratory System
Larynx
Trachea
Bronchial tubes
Alveoli
Pleura

4. Structures of Lower Respiratory System
Figure 24.2

5. Normal Biota of the Respiratory Tract
Bacteria considered “normal biota” can cause disease:
Streptococcus pyogenes
Haemophilus influenzae
Streptococcus pneumoniae
Neisseria meningitidis
Staphylococcus aureus

6. Defenses of the Respiratory Tract
Anatomical defenses:
Nasal hairs, ciliated epithelium of trachea and bronchi, mucus, coughing, sneezing, swallowing
Second and third line defenses:
Complement action in the lungs, increased levels of cytokines and antimicrobial peptides, alveolar macrophages, secretory IgA

7. The Common Cold Often called rhinitis (nose + inflammation)
In the United States, people suffer from 67 million colds per year
$40 billion per year in medical costs and 22 million missed days of work
Signs and symptoms:
Sneezing, scratchy throat, runny nose
Generally not accompanied by fever
Infection can predispose patients to secondary infections

8. Causative Agents of the Common Cold
Over 200 different kinds of viruses cause the common cold
99 serotypes of rhinoviruses, plus coronaviruses, and adenoviruses
Symptoms usually due to the immune response to the virus, not any particular virulence factors
Transmitted by droplet contact and indirect transmission
No vaccine, no specific chemotherapeutic agent

9. The Common Cold Causative Organism(s)
Approximately 200 viruses (rhinoviruses, adenoviruses, and coronaviruses)
Most Common Modes of Transmission
Indirect contact, droplet contact
Virulence Factors
Attachment proteins; most symptoms induced by host response
Culture/Diagnosis
Not necessary
Prevention
Hygiene practices
Treatment
For symptoms only
Epidemiological Features
Highest incidence among preschool and elementary schoolchildren, with average of three to eight colds per year; adults and adolescents: two to four colds per year

10. Sinusitis Sinus infection: Signs and symptoms:
Inflammatory condition of any of the four pairs of sinuses in the skull
Can be caused by allergy or infection
Patients suffering from a cold often also develop sinusitis
Signs and symptoms:
Sinus pain, nasal congestion, pressure, headache, or toothache
Discharge is opaque and can be yellow or green in color

11. Causative Agents of Sinusitis
Viruses—most common
Bacteria:
Most often normal biota
Pathogenesis due to underlying infection, buildup of fluids which provides a rich bacterial medium, and the anatomy of the sinuses which can entrap bacteria and mucus
Fungi: rare, but recognized when antibacterial drugs fail to alleviate symptoms

12. Sinusitis Causative Organism(s) Viruses
Various bacteria, often mixed infection
Various fungi
Common Modes of Transmission
Direct contact, indirect contact
Endogenous (opportunism)
Introduction by trauma or opportunistic overgrowth
Culture/ Diagnosis
Culture not usually performed; diagnosis based on clinical presentation
Culture not usually performed; diagnosis based on clinical presentation, occasionally X-rays or other imaging technique used
Same
Prevention
Hygiene
N/A
Treatment
None
Broad-spectrum antibiotics or none
Physical removal of fungus; in severe cases, antifungals used
Distinctive Features
Viral and bacterial much more common than fungal
Suspect in immunocompromised patients
Epidemiological Features
United States: affects 1 of 7 adults; between 12 and 30 million diagnoses per year
Fungal sinusitis varies with geography; in the United States: more common in SE and SW; internationally: more common in India, North Africa, Middle East

13. Pharyngitis Signs and symptoms:
Inflammation of the throat causing pain and swelling
Inflammatory packets visible on the walls of the throat, difficulty swallowing, foul breath
Viral sore throat: mild and sometimes lead to hoarseness
Bacterial: more painful, often accompanied by fever, headache, and nausea

14. The Appearance of the Throat in Pharyngitis and Tonsillitis
© Stefan Sollfors/Alamy

15. Pharyngitis Streptococcus pyogenes virulence factors:
Surface antigens of S. pyogenes mimic host proteins
Surface antigens protect the organism from being affected by lysozyme
Streptolysin O and streptolysin S: injure cells and tissues
Erythrogenic toxin: produced by lysogenized strains of S. pyogenes
Some streptococcal toxins act as superantigens

16. Streptococcal Infections
(a) © McGraw-Hill Education; (b) © Science Source
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17. Pharyngitis
Other Bacteria to Consider: Bacteria: Mycoplasma pneumonia, Arcanobacterium, Fusobacterium, Neisseria gonorrhoeae Account for remaining percentage of pharyngitis cases
Causative Organism(s)
Streptococcus pyogenes
Viruses
Common Modes of Transmission
Droplet or direct contact
All forms of contact
Virulence Factors
LTA, M protein, hyaluronic acid capsule, SLS and SLO, superantigens, induction of autoimmunity
N/A
Culture/Diagnosis
Beta-hemolytic on blood agar, sensitive to bacitracin, rapid antigen tests
Goal is to rule out S. pyogenes, further diagnosis usually not performed
Prevention
Hygiene practices
Treatment
Penicillin, cephalexin in penicillin-allergic
Symptom relief only
Distinctive Features
Generally more severe than viral pharyngitis
Hoarseness frequently accompanies viral pharyngitis
Epidemiological Features
United States: 20 to 30% of all cases of pharyngitis
Ubiquitous; responsible for 40 to 60% of all pharyngitis

18. ©BSIP/Universal Images Group/Getty Images
Diphtheria
Significant cause of morbidity and mortality for hundreds of years
Immunization with the diphtheria toxoid has caused the number of cases to decline significantly
Epidemics and smaller outbreaks have occurred due to a breakdown in immunity due to lack of vaccination
©BSIP/Universal Images Group/Getty Images
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19. Causative Agent of Diphtheria
Exotoxin manufactured by Corynebacterium diphtheriae:
Nonendospore-forming, gram- positive, club-shaped bacterium
Produces sore throat, lack of appetite, and low-grade fever
Pseudomembrane forms on the tonsils or pharynx that can completely block respiration
DTaP vaccine recommended for children with the Tdap booster for individuals 11 to 64 years
Federal Agriculture Research Centre, Germany

20. Diphtheria Causative Organism(s) Corynebacterium diphtheriae
Common Modes of Transmission
Droplet contact, direct contact, or indirect contact with contaminated fomites
Virulence Factors
Exotoxin: diphtheria toxin
Culture/Diagnosis
Tellurite medium—gray/black colonies, club-shaped morphology on Gram stain; treatment begun before definitive identification
Prevention
Diphtheria toxoid vaccine (part of DTaP, Tdap, and Td)
Treatment
Antitoxin plus penicillin or erythromycin
Epidemiological Features
United States: no cases since 2003; internationally: +/– 5000 cases per year, even though there is 83% vaccine coverage

21. Otitis Media S. pneumoniae (35%) H. influenzae (20–30%)
M. catarrhalis (10–15%)
S. pyogenes (8–10%)
S. aureus (1–2%)
Incidence of S. pneumoniae reduced by vaccine
United States: 70% of children experience at least one case before age 2; in developing world: chronic otitis media results in significant hearing loss in 100s of millions and death in approx. 30,000 per year (in absence of treatment)
Figure 24.6

22. Otitis Media Causative Organism(s) Streptococcus pneumoniae
Haemophilus influenzae
Other bacteria/ viruses
Common Modes of Transmission
Endogenous (may follow upper respiratory tract infection by S. pneumoniae or other microorganisms)
Endogenous (follows upper respiratory tract infection)
Endogenous
Virulence Factors
Capsule, hemolysin
Capsule, fimbriae
N/A
Culture/ Diagnosis
Usually relies on clinical symptoms and failure to resolve within 72 hours
Same
Prevention
Pneumococcal conjugate vaccine (PCV13)
Hib vaccine
None
Treatment
Wait for resolution; if needed, amoxicillin (high rates of resistance) or amoxicillin + clavulanate or cefuroxime
Same as for S. pneumoniae
Wait for resolution; if needed, a broad-spectrum antibiotic (azithromycin) might be used in absence of etiologic diagnosis
Distinctive Features
Suspect if fully vaccinated against other two

23. Lower Respiratory System Diseases
Bacteria, viruses, and fungi cause
Bronchitis
Bronchiolitis
Pneumonia

24. Whooping Cough Catarrhal phase: Paroxysmal phase: Convalescent phase:
Bacteria in the respiratory tract cause cold symptoms
Paroxysmal phase:
Uncontrollable coughing accompanied by a “whoop” sound
Can result in broken blood vessels in the eyes, vomiting, or even hemorrhages in the brain
Convalescent phase:
Bacteria are decreasing, but ciliated epithelia have been damaged, requiring weeks to months of recovery

25. Causative Agent of Whooping Cough
Bordetella pertussis:
Small, gram-negative rod, strictly aerobic and fastidious
Filamentous hemagglutinin: essential for attachment
Pertussis toxin: causes massive mucus production
Tracheal cytotoxin: causes direct destruction of ciliated cells

26. Whooping Cough Vaccine
Pertussis vaccine:
High vaccination coverage has kept incidence low in the United States
Vaccine does not provide lifelong protection:
Immunity wanes a few years after childhood
Increasing incidence in adult patients
Disease can be passed to infants who are not yet fully immunized

27. Tuberculosis Mycobacterium tuberculosis
Acid-fast rod; transmitted from human to human
Figure 24.8

28. Tuberculosis An ancient human disease: Now a reemerging disease
Prevalent cause of disease historically—“Captain of the Men of Death,” “The White Plague”
Streptomycin reduced rates significantly
Now a reemerging disease
HIV epidemic
Drug-resistant strains
Nearly 1/3 of the world’s population is infected

29. © McGraw-Hill Education
Primary Tuberculosis
Infectious dose: 10 bacteria
Bacteria continue to grow inside alveolar macrophages
Tubercles:
Granulomas containing a core of TB bacteria in enlarged macrophages and an outer wall made of fibroblasts, lymphocytes, and macrophages
Can become necrotic caseous lesions
Lesions can become calcified
© McGraw-Hill Education

30. Secondary (Reactivation) Tuberculosis
Bacteria remain dormant in the lungs for weeks, months, or years later Can become reactivated when immunity wanes Severe symptoms: violent coughing, greenish or bloody sputum, low-grade fever, anorexia, weight loss, fatigue, night sweats, and chest pain—“consumption” Untreated disease has a 60% mortality rate
© BSIP/Newscom

31. Tuberculosis Diagnosis
Mantoux test: shows evidence of delayed hypersensitivity after initial infection with TB
Purified protein derivative is injected under the skin and observed for evidence of an induration indicating delayed hypersensitivity
IGRA: blood test to determine T-cell reactivity to M. tuberculosis Acid-fast staining of sputum sample PCR methods Chest X-rays verify TB when other tests give indeterminate results

32. Skin Testing for Tuberculosis
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33. Tuberculosis Treatment
Active tuberculosis:
First two months: Rifampin, isoniazid, ethambutol, pyrazinamide
4 to 7 months: rifampin, isoniazid
Latent tuberculosis: isoniazid, rifampin, rifapentine
Patient noncompliance leads to drug-resistant strains
Multidrug-Resistant Tuberculosis (MDR-TB)
Extensively Drug-Resistant Tuberculosis (XDR-TB)

34. Worldwide Distribution of Tuberculosis
Figure 24.11a

35. Tuberculosis Causative Organism(s) Mycobacterium tuberculosis
MDR-TB and XDR-TB
Common Modes of Transmission
Vehicle (airborne)
Same
Virulence Factors
Lipids in wall, ability to stimulate strong cell-mediated immunity (CMI)
Culture/ Diagnosis
Culture, PCR test (Xpert®), IGRA, complemented by skin test and chest X-ray
Prevention
Avoiding airborne M. tuberculosis; BCG vaccine in other countries
Treatment
Isoniazid, rifampin, and pyrazinamide + ethambutol or streptomycin for varying lengths of time (always lengthy)
Multiple-drug regimen, which may include bedaquiline; and delamanid; in Serious Threat category in CDC Antibiotic Resistance Report
Distinctive Features
Responsible for nearly all non-MDR-TB except for some HIV-positive patients and severely immunosuppressed patients who have Mycobacterium avium complex (MAC)
Much higher fatality rate over shorter duration
Epidemiological Features
United States: approx. 10,000 cases/year, 16% of cases Whites, 84% ethnic minorities; internationally: 1.5 million deaths in 2014
United States: fewer than 100/year; worldwide: 480,000 with MDR-TB in 2014

36. Pneumonia Anatomical diagnosis:
Inflammatory condition of the lung in which fluid fills the alveoli
Can be caused by a wide variety of microorganisms
Must be able to avoid phagocytosis
Or avoid killing once inside macrophages
Viral pneumonia is usually (but not always) milder than bacterial pneumonia
Fungi can also cause pneumonia

37. Signs and Symptoms of Pneumonia
Begin with runny nose and congestion, headache, and fever Lung symptoms: chest pain, fever, cough, production of discolored sputum Patient appears pale and sickly due to pain and difficulty breathing Severity and speed of onset of symptoms depend on the etiologic agent

38. Course of Bacterial Pneumonia
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39. Causative Agents of Community-Acquired Pneumonia
Streptococcus pneumoniae accounts for 40% of community-acquired cases
Viruses account for 30%
Mycoplasma accounts for 20%
10% are caused by other organisms:
Legionella
Haemophilus influenzae
Histoplasma capsulatum

40. Community-Acquired Pneumonia
Streptococcus pneumoniae:
Small, gram-positive flattened coccus that appears in pairs
Part of the normal biota of the respiratory tract
Infection occurs when bacterium inhaled into the deep areas of the lung
Factors that enhance disease: old age, season, underlying viral respiratory disease, diabetes, chronic abuse of alcohol or narcotics
(a) © Evans Roberts; (b) © Lisa Burgess/McGraw-Hill Education

41. Community-Acquired Pneumonia
Streptococcus pneumoniae (continued):
Polysaccharide capsule prevents effective phagocytosis:
Blocks complement
Causes inflammatory fluids to build up in the lung
Vaccine is encouraged for older adults
Organism is resistant to penicillin and its derivatives, macrolides, tetracyclines, and fluoroquinolones

42. Community-Acquired Pneumonia
Mycoplasma pneumoniae:
Atypical pneumonia: symptoms do not resemble those of pneumococcal or other pneumonias
Lack a cell wall, irregularly shaped
Transmitted by aerosol droplets among individuals in close quarters
“Walking pneumonia”
Diagnosis through ruling out other causes, PCR, or serological analysis

43. Legionella pneumophila
Weakly gram-negative, displays a variety of shapes
First discovered after an American Legion convention in 1976 in Philadelphia
Widely distributed in aqueous environments:
Tap water, cooling towers, spas, ponds, other freshwater
Opportunistic disease affecting elderly people; rarely seen in healthy children and adults
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44. Legionellosis

45. Community-Acquired Pneumonia Disease
Causative Organism(s)
Streptococcus pneumoniae
Respiratory viruses
Mycoplasma pneumoniae
Common Modes of Transmission
Droplet contact or endogenous transfer
Droplet contact
Virulence Factors
Capsule
N/A
Adhesins
Culture/Diagnosis
Gram stain often diagnostic, alpha-hemolytic on blood agar
Failure to find bacteria or fungi
Rule out other etiologic agents; serology; PCR
Prevention
PCV-13 or PPSV23 vaccine
Hygiene
No vaccine, no permanent immunity
Treatment
Cefotaxime, ceftriaxone, with or without vancomycin; much resistance
None
Erythromycin
Distinctive Features
Patient usually severely ill
Usually mild
Usually mild; “walking pneumonia”
Epidemiological Features
40% of CAP cases; in 2009 H1N1 epidemic, 29% of fatalities were co-infected with this bacterium
30% of CAP cases
20%+ of CAP cases

46. Community-Acquired Pneumonia Disease
Causative Organism(s)
Legionella species
Histoplasma capsulatum
Pneumocystis jiroveci
Common Modes of Transmission
Vehicle (water droplets)
Vehicle- inhalation of fungal spores in contaminated soil
Vehicle- inhalation of fungal spores
Virulence Factors
N/A
Survival in phagocytes
Culture/ Diagnosis
Urine antigen test; culture requires selective charcoal yeast extract agar
Rapid antigen tests, microscopy
Microscopy
Prevention
Avoid soil contaminated with bird and bat droppings
Antibiotics given to AIDS patients to prevent this
Treatment
Fluoroquinolone, azithromycin, clarithromycin
Itraconazole
Trimethoprim-sulfamethoxazole
Distinctive Features
Mild pneumonias in healthy people; can be severe in elderly or immunocompromised
Many infections asymptomatic
Vast majority occur in AIDS patients
Epidemiological Features
United States: 8000 to 18,000 cases/year; internationally: 2 million cases/year
In the United States, 250,000 infected per year; 5 to 10% have symptoms
80% of untreated AIDS patients are infected

47. Health-Care-Associated Pneumonia
About 1% of hospitalized or institutionalized people develop pneumonia
Most often associated with mechanical ventilation via endotracheal or tracheostomy tube
30 to 50% mortality rate
Causative agents:
Pseudomonas aeruginosa
Acinetobacter baumannii
Klebsiella pneumoniae
Enterobacter
Escherichia coli
Staphylococcus aureus (usually MRSA)
Most cases are polymicrobial in origin

48. Prevention and Treatment of Health-Care-Associated Pneumonia
Most causes are due to aspiration from the upper respiratory tract Elevation of patients’ heads 45 degrees helps reduce aspiration of secretions Deep breathing and frequent coughing Proper care of ventilation and respiratory equipment Empiric antibiotic therapy should be started as soon as health-care-associated pneumonia is suspected

49. Health-Care-Associated Pneumonia
Causative Organism(s)
Gram-negative and gram-positive bacteria from upper respiratory tract or stomach; environmental contamination of ventilator
Common Modes of Transmission
Endogenous (aspiration)
Virulence Factors
N/A
Culture/Diagnosis
Culture of lung fluids
Prevention
Elevating patient’s head, preoperative education, care of respiratory equipment
Treatment
Varies by etiology
Epidemiological Features
United States: 300,000 cases per year; occurs in 0.5 to 1.0% of admitted patients; mortality rate in the United States and internationally is 20 to 50%

50. Viral Pneumonia
Viral pneumonia occurs as a complication of influenza, measles, or chickenpox
Viral etiology suspected if no other cause is determined

51. Respiratory Syncytial Virus (RSV)
Common in infants; 4500 deaths annually
Causes cell fusion (syncytium) in cell culture
Symptoms: Pneumonia in infants
Diagnosis: Serological test for viruses and antibodies
Treatment: Ribavirin, palivizumab

52. Respiratory Syncytial Virus
Infects the respiratory tract and produces giant multinucleated cells
Outbreaks occur around the world, peak incidence in winter and early spring
Mortality highest among premature infants, those with congenital disease, or immunodeficiency

53. Respiratory Syncytial Virus
Signs and symptoms:
Rhinitis, pharyngitis, otitis
More serious infections: progress to bronchial tree and parenchyma, symptoms of croup and difficulty breathing
Transmission:
Highly contagious and transmitted through droplet contact and fomites
Passive antibody therapy is an effective treatment.
Ribavirin is available through an inhaled aerosol

54. RSV Disease Causative Organism(s) Common Modes of Transmission
Respiratory syncytial virus (RSV)
Common Modes of Transmission
Droplet and indirect contact
Virulence Factors
Syncytia formation
Culture/Diagnosis
Direct antigen testing; RT-PCR in older children and adults
Prevention
Passive antibody (humanized monoclonal) in high-risk children
Treatment
Ribavirin or passive antibody in severe cases
Epidemiological Features
United States: general population, less than 1% mortality rates, 3 to 5% mortality in premature infants or those with congenital heart defects; internationally: 7 times higher fatality rate in children in developing countries

55. Influenza Reasons to study “the flu”:
Annual flu seasons have the potential for turning deadly for many people very quickly
Many diseases are erroneously termed “the flu”
Behavior of influenza viruses illustrates how viruses can and do cause more serious diseases than they did previously

56. Signs and Symptoms of Influenza
Headache, chills, dry cough, body aches, fever, stuffy nose, sore throat Extreme fatigue can last for a few days or weeks H1N1 “Swine flu”: not all patients had a fever, many patients had gastrointestinal distress, or developed multiorgan system failure

57. Schematic Drawing of Influenza Virus
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58. Prevention of Influenza
Three major types of influenza vaccines in the United States:
An intramuscular inactivated vaccine with three strains of influenza in it
An intramuscular inactivated vaccine with four strains
A recombinant vaccine (not made in eggs for intramuscular injection
Scientists are continually researching emerging strains to attempt to prevent a pandemic

59. Influenza Causative Organism(s) Influenza A, B, and C viruses
Common Modes of Transmission
Droplet contact, direct contact, or indirect contact
Virulence Factors
Glycoprotein spikes, overall ability to change genetically, ability to slow down immune system
Culture/Diagnosis
Viral culture (3 to 10 days) or rapid antigen-based or PCR tests
Prevention
Inactivated injected vaccine (quadrivalent and trivalent forms), inhaled live attenuated vaccine (quadrivalent), or new recombinant vaccine (trivalent)— taken annually
Treatment
Oseltamivir (Tamiflu)
Epidemiological Features
For seasonal flu, deaths vary from year to year. United States: range from 17,000 to 52,000; internationally: range from 250,000 to 500,000