Download Spring 2015-Chapter 21

DISEASES OF THE RESPIRATORY
SYSTEM
CHAPTER 21
Copyright © 2012 John Wiley &
Sons, Inc. All rights reserved.
Location of various pathogens
This is for y our reference- no questions will be asked about respiratory system structrues
Much of the upper respiratory tract contains resident microbiota. Parts of the tract are covered with mucus
and cilia that trap and move airborne material out. The lower respiratory tract lacks host microflora and is
subject to more severe and dangerous infections. Bronchioles terminate in alveoli. Any microbes entering an
alveolus can be destroyed by alveolar macrophages.
Fig. 21.1 Structures of the respiratory system.
Ureaplasma urealyticum is a major cause of urinary tract
infection
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Carefully alternating antibiotics can prevent bacteria developing resistance,
say researchers In a surprising new study, researchers show it is possible to kill
drug-resistant bacteria by alternating two antibiotics at doses that would
ordinarily boost bacterial resistance and survival when used alone or
combined. Writing in the journal PLOS Biology, the international team - led by
Robert Beardmore, a biosciences professor at the University of Exeter in the UK
- describes how carefully devised "sequential treatments" using antibiotics may
help combat the rise of resistant bacteria. "As we demonstrate, it is possible
to reduce bacterial load to zero at dosages that are usually said to be
sublethal and, therefore, are assumed to select for increased drug
resistance."The researchers decided to carry out the study because for
decades research has focused on using drugs as "cocktails" where the drugs
help each other as a "synergistic combination." But what if there is also an
effect from "sequential synergy?"For their investigation, the team used a
simple test-tube model of an Escherichia coli bacterial infection where the
bacteria had some antibiotic resistance genes. Further tests showed that while
sequential treatments did not stop drug resistance mutations in the bacteria
altogether, the first drug made the bacteria sensitive to the second drug and
thereby reduced the risk of resistance developing.
A study trialing a new generation of broadly neutralizing antibodies in humans for the first time
has shown promise as a treatment for HIV according to researchers. The results of the clinical
trial, published in Nature, have been more successful than previous HIV antibody tests in
humans, with the researchers finding that their experimental therapy can reduce the amount of
virus present in a patient's blood significantly. "What's special about these antibodies is that
they have activity against over 80% of HIV strains and they are extremely potent," says co-first
author Marina Caskey, an assistant professor of clinical investigation in the Nussenzweig
Laboratory of Molecular Immunology at the Rockefeller University, New York, NY. The antibody
in question is 3BNC117, and it has shown activity against 195 of the 237 HIV strains. 3BNC117
works by targeting the CD4 binding site of the HIV viral envelope; the CD4 receptor is the main
site of attachment of HIV to host cells. Around 10-30% of humans with HIV naturally produce
broadly neutralizing antibodies, but these only tend to develop several years after infection.
During this time, the virus is able to evolve, changing shape to protect itself from the
antibodies. It is likely 3BNC117 will need to be used in combination with other antibodies or
drugs However, the researchers noted that in two of the participants receiving the highest dose
of 3BNC117, the antibody became approximately 80% less effective in neutralizing the virus
after 28 days of treatment. This reduction may have been due to the virus evolving in order to
evade the antibody. The research group have developed a second HIV antibody and plan to test
it both alone and in combination with 3BNC117 in the future. "The goal is a once-a-year shot
for prevention and a combination approach for cure," states lead author Michel Nussenzweig,
an infectious disease physician and immunologist at the Rockefeller University.
The upper respiratory tract contains a variety of normal microflora that help
prevent infection by pathogens that may be inhaled. In addition, mucus from the
membranes that line the nasal cavity and pharynx traps microoganisms and
most particles of debris, preventing them from passing beyond the pharynx.
In the nasal cavity and bronchi, cilia extend from the epithelial cells. Because
these cells are anchored in place, they function to trap and move microbes and
particles near the cell surfaces. There mucus with debris trapped in it is
moved up into the pharynx. This mechanism, the mucociliary escalator,
allows material in the bronchi to be lifted to the pharynx and to be spit out or
swallowed.
The lower respiratory tract- From the bronchi, air passes into the lungs.
Secondary bronchi divide into smaller bronchioles, forming a branching structure
known as the bronchial tree. The bronchial tree, alveoli, blood vessels and
lymphatic vessels form the bulk of the lungs and the cavities they occupy are
covered by membrane called the pleura. Mucus from the lining of the bronchial
tree also traps foreign materials that have passed beyond the pharynx. If the
upper respiratory tract defense mechanisms fails and microorganisms get
into bronchi and bronchioles, phagocytes help remove them.
Diseases of the Upper Respiratory Tract
Bacterial upper respiratory diseases.
Pharnygitis and related infections
Pharyngitis or sore throat, is an infection of the pharynx. It is
frequently caused by a virus but is sometimes bacterial in origin. When
an infection spreads to the lungs, it is called pneumonia.
Streptococcal pharyngitis (“strept” throat). Causal agent S. pyogenes.
Figure 21-3 Strept throat
Fig. 21.3 Strep throat – white, pus-filled lesions on tonsils
Diphtheria- - Sequelae, major adverse signs that follow a disease, are common in
diphtheria: Myocarditis, an inflammation of the heart muscle (myocardium that
surrounds the heart muscle), and polyneuritis, an inflammation of several nerves,
account for deaths even after apparent recovery. Significant cardiac abnormalities
occur in 20 percent of patients.
Causative agent- Corynebacterium diphtheria infected with a prophage that
carries an exotoxin-producing genes.
This figure is also for your reference
Tubes are placed
through the tympanic
membrane (eardrum)to
promote drainage
Ear infections- otitis media if in the inner ear and otitis externa in the external
auditory canal. Most common causal agents of otitis media: S. pneumoniae, S. pyogenes
and H.influenzae (about one-half the cases). Otitis externa usually is caused by S. aureus
or Pseudomonas aeruginosa.
Fig. 21. Treating middle ear infections
DISEASES OF THE LOWER RESPIRATORY TRACT
Classic pneumonia- In the U.S. more deaths result from
pneumonia than from any other infectious disease. Pneumonia,
an inflammation of lung tissue. Several bacteria are known causes
of pneumonia- Streptococcus pneumoniae (pneumococcus),
Klebsiella pneumoniae, and Mycoplasma pneumoniae.
Once the organism gains access to damaged respiratory
epithelium it attaches by means of pili and multiplies.
Pneumococcal pneumonia is the only infectious disease in the
top 10 causes of death in the U.S. With immediate antibiotic
therapy mortality is 5% without treatment 30%.
Klebsiella pneumoniae- causes a pneumonia whose
mortality is approximately 50%.
Classification of pneumoniasDiagnosis, treatment and prevention- diagnosis is based on clinical
observations, X-rays, or sputum culture. Artificial immunity against S. pneumoniae
can be induced with the polyvalent vaccine Pneumovax which is about 80 percent
protective. (NB).
Mycoplasma pneumonia- causal agent Mycoplasma pneumoniae and it causes primary
atypical pneumonia or mycoplasma pneumonia, usually a mild pneumonia with an insidious
onset. Erythromycin and tetracycline are the drugs of choice. Penicillin has no effect because
the organism lacks a cell wall that is why mycoplasma pneumonia is called atypical
pneumoniae (pneumococcal pneumonia is treated with penicillin).
Legionnaires’ disease- causal agent legionella pneumophila- Become one of the stories in the
new microbe hunters book. The organism is weakly Gram negative, strictly aerobic, bacillus
with fastidious nutritional requirements. It does not ferment sugars. Most are free-living in soil
or water and do not ordinarily cause disease.
Tuberculosis- or TB Incidence in the U.S.- In 1993 the number of new cases reported
per month rose from 778 in January to 5130 in December. As seen below
the number of cases has declined since 1993. Before 1900
approximately one-third of adults died of TB before reaching old
age.
Fig. 21.14 TB X-ray photo
Bacterial LRT Diseases
© 2012 John Wiley & Sons, Inc. All
rights reserved.
Psittacosis and Ornithosis - psittacosis-parrot fever, a respiratory disease associated
with psittacine birds, such as parrots and parakeets. Causal agent is Chlamydia psittaci and it is
spread by direct contact, infectious nasal droplets and feces. Most cases in humans are mild and
self limiting, but some patients develop a serious pneumonia. With tetracycline mortality is about
5% untreated about 20%.
Q-fever- caused by the rickettsiae- Coxiella burnetii. This rickettsia is unusual in that it
survive for a long time outside the host by forming an endospore-like structure. See Figure 2114.
Lifelong immunity generally follows an attack of Q fever- a vaccine is available for workers with
occupational exposure.
Untreated or inadequately treated cases of Q fever can go into long periods of
remission and when reactivated can result in endocarditis which is invariably fatal.
Viral lower respiratory diseasesInfluenza- One of the greatest killers of all time was the
pandemic of swine flu (also known as Spanish flu) of 19181919 when 20 to 40 million people died.
Figure 21-18 The influenza virus a and b.
Influenza is an RNA virus that contains an envelope (membrane that surrounds the
virus). There are 3 basic types of influenza designated as type A, type B, and type
C. These types are differentiated on the basis of the antigenic make-up of the
nucleoprotein (protein associated with the RNA).
Type A flu is the most important with regard to seriousness. Projecting
from the envelope of type A flu there are two spike-like structures (as visualized by an
electron microscope) which include two glycoproteins: 1) hemagglutinin (H) and 2)
neuraminidase(N).
The hemagglutinin has the ability to agglutinate red blood cells (influenza mixed with
red blood cells results in agglutination of the RBC's). The neuraminidase is an enzyme
that cleaves neuraminic acid (sialic acid) from the ends of the sugar chains of
glycoproteins and glycolipids. The hemagglutinin is important to the virus as it
allows it to attach to the host cells;
the neuraminidase is important because it allows the virus to "detach" from the
sialic acid of lysed cells following viral replication.
The strains of influenza is most often identified by the antigenic nature of
the H and N spikes.
Immunity and prevention- Immunization is recommended for high risk
groups
Nucleoprotein determines Type A, Type B or
Type C influenza
"colorized" transmission electron micrograph
Fig. 21.20 The influenza virus
SARS (Severe acute respiratory syndrome)
A disease that killed a number of people in China in November,
2002 but it was not reported until February, 2004 when it was
reported as atypical pneumoniae. It was subsequently termed SARS
(severe acute respiratory syndrome) and spread throughout the
world. Interestingly, its current status is markedly reduced due
largely to “herd immunity”.
Single stranded RNA virus: species SARS coronavirus
Respiratory syncytial virus (RSV) is the most common and most
important and costly cause of lower respiratory tract infections in
children under 1 year and especially in male infants 1 to 6 months
old and is a pneumonia. Major outbreaks of this virus in nurseries
generally result in fatalities. For most people, RSV produces only mild
symptoms, often indistinguishable from common cold and minor
illnesses.
Hantavirus pulmonary syndrome- In May and June 1993, 24 cases of
severe respiratory illness among resident of the Four Corners area of the
southwestern U.S. were reported. Investigation identified a previously
unreported hantavirus as the cause of the disease, later named
hantavirus pulmonary syndrome (HPS). The fatality rate of 60% is
extremely high and is more than 10-fold higher than other
hantavirus diseases. The disease appears to be carried by rodents, with
a different rodent being the carrier in different parts of the country.
Acute repiratory diseaseFungal Respiratory diseases
Histoplasmosis- The soil fungus histoplasma compsulatum causes histoplasmosis. The
disease is endemic to the central and eastern U.S. (Kentucky is a major endemic site
of histoplasmosis). 75-80% of native central kentuckians will test skin
positive. H. capsulatum thrives in soil mixed with feces and especially in chicken
houses and in caves containing bat guano. Cave dust is responsible for so many
cases the disease is sometimes referred to as cave sickness. The fungus enters the
body by the inhalation of fungal spores
Histoplasmosis is an infectious disease caused by inhaling the spores of a
fungus called Histoplasma capsulatum. Histoplasmosis is not
contagious; it cannot be transmitted from an infected person or
animal to someone else