I. The Respiratory System

A. Structure & Function - 2 Regions:

1. Upper Respiratory System

a. nasal cavity - incoming air is filtered by mucus (which traps dust particles) and cilia of columnar epithelial cells (which move the particles to the throat for elimination) – called the mucociliary defense.

b. pharynx - extends from the internal nares and extends partway down the neck, where it opens into the esophagus (food tube) and the larynx; 3 regions of the pharynx: nasopharynx (uppermost portion; contains 2 internal nares & 2 openings that lead into the Eustachian tubes to equalize ear, nose, & throat air pressure),

c. oropharynx (middle portion; serves as a common passageway for air, food, drink), laryngopharynx (lowest portion; just above the esophagus and larynx).

d. associated structures:

1.) sinuses - air-filled cavities; one fxn.: produce mucus.

2.) tonsils - nodules of lymphatic tissue that form a ring at the junction of the oral cavity & oropharynx & at the junction of the nasal cavity and nasopharynx; the single adenoid tonsil is embedded in the posterior wall of the nasopharynx.

3.) epiglottis - large , leaf-shaped piece of cartilage lying on top of larynx; during swallowing the larynx elevates, causing the epiglottis to fall on the glottis(opening into larynx) like a lid, closing it off - this prevents food from entering the windpipe (trachea).

2. Lower Respiratory System

a. larynx (voice box) - mucous membranes are composed of ciliated columnar epithelial cells.

b. trachea (windpipe) - air passageway extending from the larynx; it divides into right and left primary bronchi; mucous membranes are composed of ciliated columnar epithelial cells; windpipe is supported by hyaline cartilage rings.

c. bronchi - the trachea divides in to a right primary bronchus (goes to right lung) and a left primary bronchus (goes to left lung); bronchi are similar in structure to the trachea; upon entering each lung the primary bronchi divide to form smaller bronchi - the secondary bronchi; secondary bronchi continue to branch into smaller bronchi, called tertiary bronchi, that then divide into bronchioles, which divide into even smaller terminal bronchioles.

As the tubes get smaller, several structural changes occur:

¨ Cartilage rings are replaced by cartilage plates and then the cartilage disappears all together.

¨ The mucous membrane changes from ciliated columnar epithelium to cuboidal epithelium (any debris reaching these smaller tubes must now be removed by white blood cells).

¨ As the cartilage decreases the amount of smooth muscle increases during asthma attacks the muscles go into spasm and because there is no supporting cartilage the spasms close off the air passageways - asthma medication such as albuterol targets this smooth muscle tissue).

d. lungs - lobes contain lobules (small compartments in the lungs); each lobule contains a lymphatic vessel, an arteriole, a venule, and a branch from a terminal bronchiole; terminal bronchioles subdivide into microscopic branches called respiratory bronchioles, which subbdivide into several alveolar ducts; around each alveolar duct are alveolar sacs containing alveoli (cup-shaped projections lined with epithelium); the exchange of respiratory gases between the lungs and blood takes place by diffusion across the alveolar and capillary walls; the lungs are surrounded by a membrane called the pleura.

B. Defenses & Normal Flora

1. Defenses

a. mucociliary defenses in upper respiratory system, larynx, trachea, & bronchi (cilia on that columnar epithelial cells whips up mucous.

b. macrophages in the bronchioles & alveoli.

c. IgA (antibody) protects mucous membranes.

2. Normal Flora - includes species of streptococci, lactobacilli, & some Gram negatives in the upper respiratory system; the lower respiratory system (as well as the sinuses & middle ear) is normally sterile.

C. Clinical Syndromes

1. Rhinitis - nasal inflammation; most common of all respiratory syndromes.

2. Adenoiditis - infection of adenoid tonsil

3. Pharyngitis - infection of the throat; called tonsillitis if tonsils are primarily infected; symptoms include sore throat, sometimes fever, throat may be covered by a milky white exudate, ulcers, blisters, or even a grayish membrane.

4. Sinusitis - sinuses fill with fluid & become infected.

5. Otitis media - middle ear infection; middle ear fills with fluid & becomes infected.

6. Epiglottitis - infection of the epiglottis; can cause the epiglottis to swell to many times its normal size; can cut off respiration and cause sudden death; on rare occasions laryngitis (infection of the larynx) & laryngotracheobronchitis (croup - produces a barking cough) may also cause this to occur; a severe airway narrowing near the epiglottis or the larynx causes stridor (whistling sound heard as the person breathes in).

7. Bronchitis - infection of the bronchi; produces a thick, infected mucous; cough brings up infected phlegm; fever is another symptom; complete obstruction does not occur because the bronchi are so numerous.

8. Bronchiolitis - infection of the bronchioles; inflammation narrows these tiny collapsible airways; air can enter, but has difficulty getting out; clinical signs includewheezing (musical noise heard during expiration) & trachyapnea (rapid breathing).

9. Pneumonia - infection of the lungs, with fluid & microbes replacing the air that normally fills the alveoli; normal gas exchange cannot take place; clinical signs include fever, trachyapnea, labored breathing, & a cough that may produce infected secretions; if pneumonia involves the pleura, it causes pleurisy, associated with painful breathing; caused by bacteria, viruses, and fungi.

II. Upper Respiratory Infections

A. Bacterial Causes of URI's (Bacteria are the most virulent of the u.r. pathogens, but the great thing is that they can be treated with antibiotics!)

1. Haemophilus influenzae

a. General

¨ G(-) rod

¨ needs a growth factor present in human red blood cells - hence the name Haemophilus ("blood loving")

¨ once thought to cause influenza - IT DOES NOT CAUSE INFLUENZA (“the flu”)!!

¨ major cause of virulence is the production of a capsule.

b. URI's:

1.) epiglottitis - caused by H. influenzae type B (encapsulated) – adults produce Ab's, but young children are at risk; ampicillin not effective due to plasmid-borne antibiotic resistance; conjugate vaccine (Hib) now available; babies are routinely immunized against this pathogen.

2.) sinusitis - caused by H. influenzae (nonencapsulated) strains

3.) otitis media (middle ear infection) - caused by H. influenzae (nonencapsulated) strains.

c. H. influenzae type B (encapsulated) also causes:

1.) meningitis - infection of membranes covering the brain & spinal cord; before the vaccine this bacterium was the leading cause of meningitis and mental retardation in children.

2.) cellulitis - infection of skin & subcutaneous tissues.

3.) conjunctivitis (pink eye)

2. Streptococcus pyogenes

a. General:

¨ G(+) cocci

¨ pyogenes means "pus forming"

¨ do not produce the enzyme catalase (distinguishes them from the Staphs)

¨ medically important strains are classified by their hemolytic & serological properties [see lab manual for beta vs. alpha hemolysis; S. pyogenes is usually beta hemolytic - clear zones of hemolysis]

b. URI's:

1.) pharyngitis (strep throat) - transmitted by respiratory droplets or contaminated food/drink; clinical signs: severe sore throat, fever, chills, headache, inflamed pharynx, tender lymph nodes in neck; whitish exudate on tonsils; diagnosis: latex agglutination kit that detects Ag in throat swab.

c. Complications of strep throat:

1.) scarlet fever - some strains produce an erythrogenic exotoxin that causes scarlet fever; the toxin kills cells and causes intense inflammation; was once a life-threatening illness; today's cases are mild (due to a decrease in virulence).

2.) septicemia - bacteria spread to into the blood stream

3.) rheumatic fever - occurs after the infection is over (postinfection complication); causes inflammation of joints, skin, brain, heart valves (endocarditis); leading cause of heart disease among children in developing countries; bacteria have an Ag similar to that on heart cells – wbc’s become sensitized to the bacterial Ag, then attack the heart cells; disease can be prevented if strep throat is treated with penicillin within first 10 days; r.f. patients should receive a monthly penicillin injection - they are in danger if they contact another strep infection.

d. Other diseases caused by Streptococci:

1.) Impetigo (pyoderma) – highly contagious; occurs almost exclusively in children; usually different strain than those that cause strep throat; easily treated with penicillin; usually heals without scarring, but pigment can be permanently lost; also caused by staphylococci.

3. Corynebacterium diphtheriae

a. General:

¨ G(+) irregular rod

¨ produce an exotoxin; gene for exotoxin is carried by a temperate bacteriophage, so only strains infected by this virus can produce toxin & cause diphtheria; toxin interferes with protein synthesis in eukaryotic cells.

b. Diphtheria

¨ transmission: respiratory droplets; bacteria is noninvasive, but deeper tissues are affected because they absorb the toxin

¨ clinical signs: infected throat swells & becomes covered by a tough, grayish pseudomembrane composed of dead human cells & microbes [membranous pharyngitis]; swollen tissue & pseudomembrane can obstruct airway, leading to death by suffocation; fatal complications can also result if toxin enters the blood stream and damages other organs; treatment: horse antitoxin (serum sickness is a potential risk)

¨ prevention: toxoid vaccine - produced by treating toxin with formaldehyde - part of DPT (diphtheria-pertussis-tetanus) series given to infants; immunization does not confer lifelong immunity - adults should have a booster every 10 years!

4. Bacterial causes of the common cold: Mycoplasma pneumoniae, Coxiella burnetii.

Remember that most colds are viral.

B. Viral Causes of URI's - more common & less serious than bacterial infections; treatment is a challenge (antibiotics are worthless). (See Chapter 10 on these groups of viruses)

1. Rhinoviruses

a. General

¨ RNA viruses

¨ named for portal of entry - rhino means "nose"

¨ primary cause of commn cold - causes 1/4 to 1/2 of colds.

¨ about 100 different serotypes (have different antigens in capsids), with new types continuing to be identified.

b. Common Cold - clinical signs: sneezing, rhinorrhea (excess nasal mucous), nasal congestion, sore throat, fever, headache; malaise (feeling of general discomfort) due to interferons produced to combat the infection; cold typically lasts 1 week; transmission mainly by direct contact (hand to hand) or fomites; also by respiratory droplets; treatment: none - recovery depends on individual's immune system - antibiotics are useless; over-the-counter medications only help alleviate symptoms.

2. Coronaviruses - also cause the common cold.

a. General

¨ named for prominent spikes on their outer surface

¨ difficult to isolate in cell culture

¨ cause 10-15% of colds in adults (also cause pneumonia & intestinal infections).

3. Other viral causes of the common cold: coxsackieviruses, echoviruses, adenoviruses, myxoviruses.

III. Lower Respiratory Infections

A. Bacterial Causes

1. Streptococcus pneumoniae [pneumococcus]

a. General:

¨ G(+), lancet-shaped diplococci (paired diplococci with pointed ends)

¨ do not produce catalase; optochin sensitive; alpha hemolysis

¨ part of normal flora of 10% of population

¨ capsule is critical factor in virulence

¨ causes 90% of acute bacterial pneumonias

b. Pneumococcal Pneumonia

1.) transmission - respiratory droplets

2.) clinical syndrome: bacteria in the lung trigger an intense inflammatory response; leaky capillaries allow fluid, blood cells, & serum proteins to flow into the alveoli, filling them; the affected region becomes consolidated, giving the impression of a solid organ when tapped, listened to, or penetrated by x-rays; difficult & labored breathing occur; sputum is bright with blood; 30% of untreated patients die - suffer from unrelenting fever & worsening respiratory problems;pneumococcal sepsis (bacteria enter the bloodstream) can occur - particularly in patients with no spleen - spleen filters out bacteria for macrophages to engulf and process Ag (Ag presentation in antibody-mediated response).

3.) treatment - penicillin is the standard treatment, although some resistant strains do exist.

4.) vaccine: Pneumovax - polyvalent (multiple-Ag) vaccine.

5.) bacteria that cause the same clinical syndrome: Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, E. coli .

2. Mycoplasma pneumoniae

a. General

¨ lack a cell wall

¨ adhere to epithelial cells; do not invade deeper tissues

¨ grow slowly in lab

¨ grows in trachea; transmitted in respiratory droplets

b. Mycoplasma Pneumonia (Primary Atypical Pneumonia or "Walking Pneumonia")

1.) clinical syndromes: occurs most frequently in school-age children & teens; comes on gradually; mild; causes headache, low-grade fever, persistent dry cough; shows a patchy pattern in chest x-rays rather than dense consolidation of an entire lobe; rarely fatal; viruses, chlamydiae, & rickettsiae cause similar atypical pneumonias.

2.) treatment: tetracycline; erythromycin for pregnant women & young children; not sensitive to penicillins & cephalosporins because they lack a cell wall.

3. Chlamydia psittaci

a. General

¨ obligate intracellular parasites; can only be cultured in lab in chick embryos; therefore, infections are usually diagnosed serologically.

¨ psittaci means "parrot"

b. Ornithosis, Psittacosis, or Parrot Fever

1.) transmission - microbe commonly infects all types of birds; usually does not produce illness in bird; disease spreads when infected bird become stressed and microbe is excreted in bird's droppings; humans inhale microbe from droppings; occupational hazard for bird handlers or those working in poultry industry.

2.) clinical syndrome - fever, headache, chills, cough; can progress to persistent high fever, mental confusion, & marked shortness of breath.

3.) prevention - antibiotic supplements in feed & antibiotic treatment of imported birds have prevented many infections.

4.) Coxiella burnetii

a. General

¨ rickettsia - life cycle requires both insect (tick) & vertebrate hosts; obligate intracellular parasite

¨ "Q" stands for query, as etiologic agent was unknown.

¨ Another species causes trachoma, a blinding conjunctivitis.

b. Q Fever

1.) transmission - humans become infected by inhaling the microbe from infected animal placentas, feces, amniotic fluid, or milk (they can survive the pasteurization process).

2.) clinical syndrome: atypical pneumonia; can't be distinguished clinically from mycoplasmal pneumonia or parrot fever; rare disease; rarely causes death.

5. Legionella pneumophila

a. General

¨ In 1976, 183 American Legion conventioneers in Philadelphia became ill with a mysterious form of pneumonia.

¨ this flagellated microbe can be seen only by means of special stains, such as silver-impregnation stains or IFA.

¨ can live inside macrophages; multiply as an intracellular pathogen.

b. Legionellosis or Legionnaires' disease

1.) transmission - lives in natural & artificial water supplies; survives heat & chlorination; infections occur when waterborne microbes become aerosolizes & are inhaled (water-cooled air conditioning systems).

2.) clinical syndrome - minor symptoms in most; some develop a virulent pneumonia - sudden onset, weakness, headache, high fever, cough, shaking chills; x-rays show consolidation of an entire lobe; smokers & alcoholics are particularly susceptible.

3.) treatment - resistant to penicillin & cephalosporins; early diagnosis is critical in order to treat with erythromycin.

6. Bordetella pertussis

a. General

· G(-) coccobacillus

· produces exotoxins

· pertussis means "intensive cough"

b. Pertussis (Whooping Cough)

1.) transmission - respiratory droplets; highly contagious

2.) clinical syndrome - uncontrollable fits of coughing (paroxysms)

3.) treatment - by the time diagnosis occurs, the toxin has caused considerable damage, so antibiotic treatment does little to shorten the illness; supportive nursing care is the only treatment.

4.) prevention - infants are protected by the DPT immunization series; vaccine has side effects (fever, convulsions in some); an acellular vaccine genetically engineered vaccine is being developed.

7. Mycobacterium tuberculosis

a. General

· rod-shaped obligate aerobe; id. by Robert Koch

· waxy cell capsule contains mycolic acids; called "acid fast;" require special staining techniques; waxy capsule allows microbe to survive prolonged drying and resists digestion by lysozymes inside a phagocyte; can remain viable for as long as 8 months upon entering the air when a patient coughs.

· other species also cause tuberculosis.

b. Tuberculosis - leading killer among infectious diseases today; can also affect the lymphatic, the genitourinary, the skeletal, & the nervous systems.

1.) transmission - respiratory droplets

2.) clinical syndrome:

a.) primary infection - microbes enter the lungs & are phagocytized by alveolar macrophages, but are not killed; several weeks later, T cells are activated, eliciting a cell mediated immune response & tuberculin hypersensitivity (Type IV, delayed); cellular immunity helps control the infection - hypersensitivity causes most of the tissue damage associated with severe cases; the bacteria are isolated within nodules called tubercules or granulomas(dense collections of activated macrophages & lymphocytes); if host cells in the center of a tubercle die, the dead tissue looks dry & crumbly, like cheese (called caseation necrosis - "cheeselike death"); bacteria can persist in these granulomas for many years; progressive primary infection can occur - cellular immunity fails to control the microbes and they spread to other parts of the body; miliary tuberculosis is a life threatening form of the disease - infection sites are so numerous, they look like seeds of millet (grain) scattered throughout the body.

b.) secondary (reactivation) infection - walled-off bacilli inside old tubercles may escape; the ensuing hypersensitivity reaction can destroy the lungs; patients suffer a chronic cough (consumption); without treatment, the disease is fatal.

3.) prevention

1.) BCG vaccine - Bacilllus Calmette-Guerin - made from attenuated M. bovis; not entirely reliable; not widely used in U.S., but is used in other parts of the world.

2.) Skin testing

4.) treatment - people who have a positive skin test but do not have active tuberculosis are treated with a single drug (ex. isoniazid) for 1 yr. (prevents reactivation infection); people with active infections receive multiple drug therapy for 2 years.

Important: The number of cases in the U.S. is on the rise. New drug-resistant strains have been identified; have emerged in patients who did not finish their full course of medication and are lost to medical follow-up.

B. Viral Causes

1. Influenza virus

a. General

· orthomyxovirus family, enveloped virus

· composed of 8 separate pieces of RNA; this and its ability to infect an already infected cell enables the virus to undergo genetic recombination (antigenic shift); this contributes to the virus's genetic variability & potential to cause epidemics.

· different strains: A (most severe; responsible for pandemics), B (common cause In children), & C

b. Influenza (Flu)

1.) transmission - animal reservoirs are critical; Type a is widespread in birds, which transmit it to pigs, who transmit it to humans (you may have heard of the "swine flu").

2.) clinical syndrome - fever, headache, muscle aches, cough; tracheobronchitis; person becomes prone to secondary bacterial infections because ciliated columnar epithelial cells are killed; can also cause pneumonia.

3.) treatment - antibiotics only prevent secondary bacterial infections; antiviral agent amantadine can speed recovery if it is administered during the first 2 days of illness.

4.) prevention - immunization (only 70% of those vaccinated are protected); changing Ag's required a new vaccine every year.

2. Parainfluenza virus

a. General

· paramyxovirus family; RNA viruses; enveloped

· some cause common cold

b. Croup

1.) transmission - respiratory droplets

2.) clinical syndrome - laryngotracheobronchitis causes the airway to narrow at and below the vocal cords; extremely severe cases can resemble epiglottitis, but the illness is usually milder and more gradual in onset; common in toddlers; loud, barking cough; symptoms are worse at night when mucous accumulates (take them outside in the cold - cold air constricts blood vessels; cool mist humidifier thins mucous).

3.) treatment/prevention - supportive nursing care; no immunization.

3. Respiratory Syncytial Virus (RSV)

a. General

· paramyxovirus

· infected respiratory tissues develop syncytia (large, abnormal cells with multiple nuclei)

b. Bronchiolitis - most common cause of fatal lower respiratory infection in young children/infants.

1.) transmission - hand to hand; respiratory droplets; nosocomial infections.

2.) clinical syndrome - infants under 6 mo. suffer the most; wheezing; rapid breathing.

3.) treatment/prevention - supportive nursing care; no immunization.

4. Hantavirus

a. General - arboviruses; named for Hantaan River in North Korea

b. Hantavirus Pulmonary Syndrome - appeared mysteriously in the early 1990's in the 4 Corners area of the American Southwest.

1.) transmission - virus occurs in the long-tailed deer mouse; the mice shed the virus in their urine, feces, & saliva, and people contract the disease by inhaling aerosolized viral particles.

2.) clinical syndrome - fever, muscle aches, respiratory distress; 70% of cases result in death within 5-6 days; death caused by catastrophic lung failure; capillaries leak profusely & fluid fills the air spaces.

IV. Other Viral Diseases

(Portal of Entry is the Respiratory System, but Usually Affect other Systems)

1. Mumps - paramyxovirus; transmitted in saliva or respiratory secretions; enters a new host through the respiratory system; infects salivary glands; swelling of glands results, along with mild pain and sometimes fever; sometimes enters bloodstream and infects other tissues; in adult males may infect the testes (inflammation called orchitis); in rare cases it infects the inner ear, causing deafness; part of MMR (mumps, measles, rubella) vaccine given at 15 mo.

2. Rubeola Measles (= Measles) - paramyxovirus; one of most communicable diseases known; virus is inhaled; virus multiplies in respiratory tract, then spreads throughout the body, multiplying in lymphoid tissue; virus fuses cell to one another - can be seen under the microscope; symptoms: fever, cough , runny nose, conjunctivitis ("pink eye"), Koplik spots appear around mouth; rash appear first on face and gradually spreads downward to cover the entire body; complications such as ear infections, pneumonia, & encephalitis can occur; part of MMR vaccine given at 15 months.

3. Rubella measles (German Measles) – paramyxovirus; virus is inhaled; incubation period is 2 weeks; symptoms: mild fever, rash that lasts less than 3 days, swollen lymph nodes; complications are rare; not as communicable as measles or chickenpox; infection during first 3 months of pregnancy can cause a miscarriage or birth defects; part of MMR vaccine given at 15 months.

4. Varicella Zoster (Chicken pox & Shingles) - like herpes, this virus establishes a latent infection in nerve cells that can be reactivated later; people infected for the first time develop a generalized infection called varicella or chickenpox, that produces blisters all over the body; recovery is complete, but the virus remains latent in neurons; adults who come down with chickenpox can contract a life threatening viral pneumonia; chickenpox during pregnancy is dangerous; reactivation of a latent varicellla zoster infection is called shingles; it is usually brief, but can be painful; passive immunization with varicella zoster immune globulin (VZIG) greatly decreases the severity of chickenpox if administered within 3 days of exposure; an active vaccine has been approved in the U.S. & is currently being administered.

5. Smallpox (Variola virus) - virus is inhaled; less communicable than measles, but very hardy; disease was eradicated in 1979; a closely related poxvirus, vaccinia, is used for smallpox immunization; severity of disease depends on strain; produces a high fever and a severe blistering rash, killing about half of its victims.

6. Infectious Mononucleosis ("Kissing Disease") - caused by Epstein-Barr Virus (EBV); associated with lymphatic system; virus establishes a latent infection in B cells symptoms: fever, fatigue, sore throat, swollen lymph nodes, enlarged spleen (spleenomegaly - appears 1-2 mo. after infection); in most patients, the illness lasts 4-6 weeks; EBV is one of the few viruses proved to be oncogenic (Burkitt's lymphoma, nasopharyngeal carcinoma, B cell lymphoma).