Structure and Function of the Respiratory System

• Normal Microbiota suppress the growth of potentially pathogenic

microorganisms- competition, inhibitory subs.

• Microbial Diseases of the Resp. Sys.Pharyngitis LaryngitisTonsillitisSinusitisEpiglotittis – most threatening, haemophilus influenzae

type b (opportunistic pathogens)

Bacterial Diseases of the URS

Stretoccocal Pharyngitis (Strep throat)• Group A streptoccocus (GAS)- Gram-positive bacterial group- consists solely of streptoccocus

pyogenes- Resistant to phagocytosis- Produce streptokinases (lyse fibrin clots) and streptolysins

(cytotoxic to tissue cells, RBCs, and protective leukocytes)• Intervention- rapid antigen detection test- throat swabs, enzyme immunoassay

• Characterization- inflammation, fever,

otitis media• Transmission

- Respiratory secretions• Treatment

- penicillin

Scarlet Fever• Streptococcus pyrogenes strain- Produces erythrogenic (reddening)

toxin- scarlet fever- The strain has been lysonized by a

bacteriophage- Genetic information of bacteriophage

has been incorporated into the chromosome of the chromosome

• Characteristics- Pinkish red skin- High fever- Tongue- spotted strawberry-like

appearance

Diphtheria• Corynebacterium diphtheriae- gram-positive, non-endospore forming rod- Pleomorphic, frequently club-shaped, it stains unevenly• Characteristics- tough grayish membrane (throat)- Contains fibrin, dead tissue, and bacterial cells- Exotoxin (lysonized by a phage) – interferes with protein

synthesis• Treatment- antibiotics, antitoxin, DTaP vaccine• Transmission- Transmitted through droplets

Cutaneous Diphtheria- The bacteria causes slow-healing ulcerations covered by a gray

membrane- C. diphtheriae infects the skin, usually at a wound or similar skin

lesion, and there is minimal systemic circulation of the toxin

Otitis Media• S. pnneumoniae, H.

influenzae, Moraxella catarrhalis, S. pyrogenes, S. aureus

• Formation of pus- builds up pressure against the eardrum- inflamed and painful

• More frequent in childhood

• Treatment- antiobiotics,

pneumococcal vaccine

Viral Diseases of the URS

COMMON COLD• Rhinoviruses, coronaviruses• Rhinoviruses – common, thrive at a temp. below that of

normal body temp.- URS• Symptoms: sneezing, excessive nasal secretion, congestion• Transmission: airborne droplets

* temp.-cilia (ciliary escalator) work slowly• Treatment: supportive,

* new approach- improved insight into the host- virus attachment mechanisms

Bacterial Diseases of the LRS

PERTUSSIS (WHOOPING COUGH)

• Bordetella pertussis- Small, obligately aerobics,

gram-negative cocco-bacillus- Possess a capsule- Attached specifically to

ciliated cells- Produces several toxins:

* tracheal cytotoxin- destroy ciliated cells

* pertussis toxin- enters the blood stream, systemic symptoms the disease

• Stages

* Catarrhal stage- resembles a common cold

* Paroxysmal stage- prolonged sieges of coughing, ciliary action is compromised, mucus accumulates

* Convalescence stage- last for months• Treatment

* DTP- childhood vaccination

* Tdap- for adolescents an adults

* DTaP- new accellular vaccine for children

* erythromycin- antibiotic

- not effective after the onset of the paroxysmal stage

- may reduce the transmission

TUBERCULOSIS • Mycobacterium

tuberculosis- Slender rod, obligate

aerobe- Surface of liquid

media- moldlike (growth)

- Cell wall- contains large amounts of lipids- resistance to environmental stresses

Pathogenesis of Tuberculosis

• Coughing- spreads the infection by bacterial aerosols

* sputum- may become bloodstain, tissues are damaged, blood vessels rapture- fatal hemorrhaging

• Miliary tuberculosis - disseminated infection

* weight loss, general loss of vigor• Treatment

* WHO - min. of 6 months of antibiotic therapy

- isoniazid, rifampin

* FDA - approved first-line drugs

- pyrazinamide, rifapentine, ethambutol

• There are 5 essential drugs in use in the treatment of Mycobacterial infections and they are referred to as first-line therapeutic drugs- streptomycin, rifampicin, isoniazid, pyrazinamide and ethambutol.

• These drugs act on two key properties of mycobacterial cell growth:

* The first is the synthesis of the cell wall of the bacterium

* The second is the synthesis of bacterial proteins.• Isoniazid, pyrazinamide and ethambutol- interfere with

the synthesis of key components of the bacterial cell wall

• Streptomycin and rifampicin - interfere with protein synthesis, inhibits the

transcription of messenger RNA and the translation of messenger RNA to produce bacterial proteins.

• Second-line therapeutic drugs - with higher toxicity- essential for the treatment of drug resistant forms of

mycobacteria

• Prolonged treatment- Tubercle bacillus grows very slowly

or is dormant- Bacillus may be hidden for a long

periods- macrophages, and other locations that cannot be reached by antibiotics

* multiple- drug therapy- minimize the emergence of resistant strains

* at present- diarylquinoline drug – impedes the synthesis of

ATP in mycobacteria, effective in killing both dormant and actively growing bacilli

• Diagnosis – tuberculin skin test

• Bovine tuberculosis- Mainly cattle- Contaminated milk or food- Primarily affects the bones or lymphatic system- Common manifestation: hunchbacked deformation of

the spine- BCG vaccine

BACTERIAL PNEUMONIAS• Typical pneumonia- Streptococcus

pneumoniae• Atypical pneumonia- other

microorganisms• Pneumonias are named after the portions

the infect

ex. bronchopneumonia Pneumococcal pneumonia• S. pneumonia- gram-positive, ovoid

bacterium- Presence of dense capsule- resistant to

phagocytosis• Symptoms: high fever, breathing diffculty,

chest pain

* lungs have reddish appearance• Treatment: microlides, fluoroquinolones

Haemophilus influenzae pneumonia• H. influenzae- Gram-negative coccobacillus• Symptoms: resemble pneumococcocal pneumonia• Treatment: cephalosporin- resistant to the beta- lactamases

produced by H. influenzae

Mycoplasmal pneumonia• Mycoplasma pneumoniae- lack cell walls• Symptoms: low fever, cough, headache• Treatment tetracycline

Legionellosis • Legionella pneumophila- gram- negative rod, aerobic- Capable of replication within macrophages• Characteristics- Can grow in water conditioning system- Can inhabit the water lines of many hospitals (temp. of hot

water lines- 43-55 oC)

* copper- silver ionization system

• General characteristics of the disease- High fever (40.5 oC), cough and general symptoms of

pneumonia- Pontiac fever- another form of legionellosis, characterized

by fever, muscular aches, cough- Treatment: erythromycin, microlide antibiotics

(azithromycin)

Psittacosis (ornithosis)

• Contracted from birds

• Chlamidophila psittaci

- gram-negative, obligate intracellular bacterium

- Formation of elementary body- resistant to environmental stress

• Transmission: airborne

* droppings and other exudates of fowl – inhalation

* many birds carry the pathogen in their spleen, becoming ill only when stressed

• Treatment: tetracyclines- humans and animals

Chlamydial pneumonia• Chamidophila pneumoniae• Symptoms: resembles mycoplasmal pneumonia- formation of antibodies against the organism- indicates that it

is a common illness• Treatment: tetracycline

Q fever• In the absence of an obvious cause- Q (query)• Coxiella burnetii- Obligately parasitic, intracellular bacterium• Symptoms: high fever, headaches, muscle aches, and coughing• Transmission: airborne, tick bites- Cattle ticks- spread the disease through dairy herds- Dairy herds shed microbes in their feces, milk and urine- Humans- ingestion of unpasteurized milk, inhaling aerosolsof

microbes (calving time)

• Endospore like body- heat resistance• Treatment: doxycycline

* chronic infections- doxycycline + chloroquine

* chloroquine- raises pH of the phagosome, increasing doxycycline’s efficiency

Melioidosis• Burkholderia pseudomllei- Gram-negative rod, moist soil• Characteristics- Septic shock, abscesses in various body tissues, severe sepsis,

encephalitis• Transmission - Inhalation

* incubation period can be very long• Treatment

- ceftazidime- beta- lactam antibiotic

Viral Diseases of the LRS

Viral pneumonia- Can occur as a complication of influenza, measles, or even

chicken pox

Respiratory Syncytial virus• Syncytial virus• Symptoms: coughing and wheezing• Treatment: ribavirin- antiviral drug

palivizumab- humanized monoclonal antibody, high- risk patients

• The influenza virus

• Influenzavirus- 8 separate RNA segments with differing lengths- enclosed by: inner layer (protein) and outer layer (lipid bilayer)- projections: HA (hemagglitinin) spikes, NA (neuraminidase)

spikes • Viral strains- Identification: variation in the HA and NA antigens- Different forms of the antigen are assigned numbers- Subtypes: HA- 16, NA- 9

* substantial alteration in the protein make-up of the spike

• Antigenic Shifts- Cause by major genetic recombination

* viral RNA- 8 segments- Recombination: more than 1 strain

ex. * hemagglutinin spikes bind to sialic acids on the surface of the epithelial cells

* sialic acids differ in human and birds

* swine- “mixing vessel” – recombination, reassortment

- RNA viruses have high mutational rates • Antigenic drift- Minor annual variations in the antigenic make up- 1 amino acid

in the protein make of the HA and the NA spike- Cause of mutation: selective pressure by antibodies

• Classification: A, B, and C

- According to the antigens of their protein coats

- Type A- responsible for major pandemics

- Type B- geographically limited, milder infection

• Treatment- Amantadine and rimantadine- Zanamivir (Relenza), oseltamivir (Tamiflu)- inhibitors of

neuramidase/ replication

Fungal Diseases of the LRS

Histoplasmosis • Histoplasma capsulatum- Produces conidia- Dimorphic- 2 forms of growth - Yeastlike form survives and multiplies in macrophages• Transmission: airborne conidia• Treatment: amphotericin B

• nnn

Coccidioidomycosis• Coccidioides immitis- Dimorphic fungus- Found in dry, alkaline soils- In tissues: forms a thick-walled body- spherule- In soil: forms filaments that reproduce by the formation of

arthroconidia• Symptoms: chest pain, coughing, and weight loss• Transmission: dustborne/ wind• Treatment: self-limiting, amphotericin B

Pneumocystis pneumonia• Pneumocystis jirovecii- Found mostly in the lining of the alveoli- Forms a thick walled cyst in which in spherical intracystic

successively divide• Treatment

- trimethoprim- sulfamethoxazole

Blastomycosis• Blastomyces dermatitidis- Dimorphic fungus- Most infections are asymptomatic- Resembles bacterial pneumonia- Cutaneous ulcers commonly appear, extensive abscess

formation, tissue destruction- Amphotericin B