DISEASES OF THE RESPIRATORY SYSTEM CHAPTER 21 Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

DISEASES OF THE RESPIRATORY SYSTEM

CHAPTER 21

Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Fig. 21.1 Structures of the respiratory system.

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.

Location of various pathogens

This is for y our reference- no questions will be asked about respiratory system structrues

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 infectionsPharyngitis 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.

Fig. 21. Treating middle ear infections

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.

Tubes are placed through the tympanic membrane (eardrum)to promote drainage

This figure is also for your reference

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 pneumonias- Diagnosis, 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 21-14.

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 diseases-Influenza- One of the greatest killers of all time was the pandemic of swine flu (also known as Spanish flu) of 1918-1919 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

Fig. 21.20 The influenza virus

"colorized" transmission electron micrograph

Nucleoprotein determines Type A, Type B or Type C influenza

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 disease- Fungal 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