Topic: Respiratory and Systemic Disease 1 Structures of the Respiratory System Function of the Respiratory System Exchange of gases between the atmosphere and the blood Respiratory system divided into two main parts Upper respiratory system Collects air, filters contaminants from the air, and delivers it to the lower respiratory organs Lower respiratory system 2 Structures of Upper Respiratory System, Sinuses, and Ears Components of the upper respiratory system Nose external portion of the respiratory system Nasal cavity lined with hairs and a ciliated mucous membrane to filter and trap particles and microbes Pharynx lined with a ciliated mucous membrane that pushes contaminants into the digestive system Tonsils aggregations of lymphoid tissue Mucus contains antimicrobial chemicals 3 1
Structures of the Lower Respiratory System Components of the lower respiratory system Larynx contains the vocal cords Trachea, bronchi, bronchioles series of tubes that allow movement of air through to the lungs Alveoli Air sacs of the lungs where oxygen from air enters the blood while carbon dioxide diffuses from the blood into the alveoli to be exhaled Diaphragm muscle involved in breathing Protective components include a ciliated mucous membrane, alveolar macrophages, and secretory antibodies 4 Structures of the Respiratory System 5 Structure of the Respiratory System Normal Microbiota of the Respiratory System Lower respiratory system Typically microorganisms are not present Upper respiratory system Normal microbiota limit growth of pathogens Normal microbiota may be opportunistic pathogens Examples of normal microbiota Haemophilus influenzae can colonize the nose Staphylococcus aureus is present as normal microbiota in some individuals without causing disease Diphtheroids can colonize the nose and nasal cavity 6 2
Streptococcal Respiratory Diseases Sore throat, difficulty swallowing; may progress to scarlet or rheumatic fever Pathogen and virulence factors Caused by Group A streptococci (S. pyogenes) Virulence factors include M proteins, hyaluronic acid capsule, streptokinases, C5a peptidase, pyrogenic toxins, streptlysins Pathogenesis Typically occur when normal microbiota are depleted, large inoculum is introduced, or adaptive immunity is impaired 7 Streptococcal Respiratory Diseases (cont.) Streptococcal Respiratory Diseases Epidemiology Spread via respiratory droplets Occurs most often in winter and spring Often confused with viral pharyngitis Penicillin is an effective treatment 8 Streptococcal Respiratory Diseases: Strep. pyogenes & Strep Throat! 9 3
Diptheria Agent - Corynebacterium diptheriae (G+, non-spore forming bacillus, v-shapes & pallisades) Sore throat, oozing fluid that hardens into a pseudomembrane that can obstruct airways Cirulence factors Virulent C. diptheriae produce diphtheria toxin, prevents polypeptide synthesis and causes cell death. 10 Diptheria pseudo-membrane presentation 11 Characteristic Corynebacterium stain appearance 12 4
Diptheria (cont.) Pathogenesis and epidemiology Spread person to person via respiratory droplets or skin contact Immunocompromised or nonimmune individuals develop symptomatic infections Diagnosis based on presence of a pseudomembrane Treated by administration of antitoxin and antibiotics Immunization is an effective prevention 13 Sinusitis and Otitis Media Sinusitis: pain and pressure of the affected sinus accompanied by malaise Otitis media: severe pain in the ears Pathogen and virulence factors Caused by various bacteria such as Streptococcus pneuomoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis 14 Sinusitis and Otitis Media (cont.) Pathogenesis and epidemiology Bacteria in the pharynx spread to the sinuses via their connection with the throat Sinusitis is more common in adults; otitis media is more common in children Symptoms often diagnostic No known way to prevent sinusitis 15 5
The Common Cold >200 varieties Endemic Sneezing, runny nose, congestion, sore throat, malaise, and cough Pathogens and virulence factors Rhinoviruses are the most common cause, although numerous viruses cause colds Pathogenesis Cold viruses replicate in and then kill infected cells 16 The Common Cold (cont.) Epidemiology Transmitted via coughing/sneezing, fomites, or person-to-person contact Signs and symptoms are usually diagnostic Treatment is mainly supportive Pleconaril can reduce duration of symptoms Hand antisepsis is important preventive measure 17 Bacterial Diseases of the Lower Respiratory System Lower respiratory organs are usually axenic When bacterial infection of the lower respiratory system occurs life-threatening illness can result 18 6
Bacterial Pneumonias Inflammation of the lungs accompanied by fluid filled alveoli and bronchioles Can be described by the affected region or the organism causing the disease For example, lobar pneumonia involves entire lobe of the lung Bacterial pneumonias are the most serious and the most frequent in adults 19 Pneumoccocal Pneumonia Fever, chills, congestion, cough, chest pain, and short, rapid breathing Pathogen and virulence factors Caused by Streptococcus pneumoniae Virulence factors include adhesins, capsule, pneumolysin Pathogenesis and epidemiology Infection occurs by inhalation of bacteria Bacterial replication causes damage to the lungs Penicillin is the drug of choice for treatment Vaccination is method of prevention 20 Strep pneumoniae - Bacterial pneumonia of the Lower Respiratory System 21 7
Primary Atypical (Mycoplasmal) Pneumonia Atypical symptoms including fever, malaise, sore throat, excessive sweating Pathogen and virulence factors Caused by Mycoplasma pneumoniae Virulence factors include an adhesion protein No cell wall, stains G- but actually G+! Epidemiology Nasal secretions among individuals in close contact spread the bacteria Treated with tetracycline and erythromycin Prevention is difficult because individuals can be infective despite lack of symptoms 22 Mycoplasma pleomorphism in Lower Respiratory System 23 Klebsiella Pneumonia Typical pneumonia symptoms combined with a thick, bloody sputum and recurrent chills Pathogen and virulence factors Caused by Klebsiella pneumoniae G- rod, leading cause of noscomial infections Virulence factors include a capsule Pathogenesis and epidemiology Immunocompromised individuals at greatest risk for infection Treated with antimicrobials Prevention involves good aseptic technique by health care workers 24 8
Klebsiella pneumoniae capsule 25 Other Bacterial Pneumias Cause Haemophilus influenzae, Staphylococcus aureus, Yersinia pestis, and Chlamydia species Portal of entry inhalation, also via blood with Y. pestis Signs/Symptoms typical pneumonia symptoms with frothy, bloody sputum in the case of Y. pestis Incubation period variable depending on cause, although Y. pestis can produce symptoms in hours Susceptibility typically young children most susceptible Treatment antibiotic treatment Prevention good hygiene; vaccine available for H. influenzae 26 Strep pneumonia is a diplococcus 27 9
Legionnaires Disease Typical pneumonia symptoms and possible complications of the gastrointestinal tract, CNS, liver, and kidneys Pathogen and virulence factors Caused by Legionella pneumophila Pathogenesis L. pneumophila kills human cells, causing tissue damage and inflammation 28 Epidemiology Legionnaires Disease (cont.) The elderly, smokers, and immunocompromised individuals are at increased risk for infection Quinolones or macrolides are the drugs of choice for treatment Reduction of bacterial presence in water is successful control measure 29 Legionella pneumophilia colonies on Charcoal Yeast Extract 30 10
Tuberculosis (M. tuberculosis) Pathogenesis M. tuberculosis can remain viable for long periods in aerosol drops (also has non pneumonia form) Three types of tuberculosis Primary tuberculosis initial case of tuberculosis disease Secondary tuberculosis reestablished tuberculosis Disseminated tuberculosis tuberculosis involving multiple systems Epidemiology Immunocompromised individuals are most at risk Tuberculosis is the leading killer of HIV+ individuals 31 M. Tuberculosis, acid-fast stain shows corded (parallel) growth 32 Primary TB Infection Progression 33 11
TB Diagnosis 34 Pertussis (Whooping Cough) Initially cold-like, then characteristic cough develops Pathogen and virulence factors Bordetella pertussis is the causative agent Virulence factors include various toxins including pertussis toxin, adenylate cyclase toxin, dermonecrotic toxin, and tracheal cytotoxin Pathogenesis Four phases incubation, catarrhal, paroxysmal, and convalescent 35 Epidemiology Pertussis (Whooping Cough) (cont.) Highly contagious; the bacteria spread through the air in airborne droplets Symptoms are usually diagnostic Treatment is primarily supportive Prevention is with the DTaP vaccine 36 12
Bordetella pertussis in cilia of tracheal epithelium 37 Inhalational Anthrax (as opposed to cutaneous) Resemble a cold or flu but progress to severe coughing, shortness of breath, shock, and death Pathogen and virulence factors Bacillus anthracis is the causative agent Virulence factors include a capsule and secretion of anthrax toxin Pathogenesis and epidemiology Anthrax not spread from person to person Acquired by endospore contact or inhalation 38 Inhalational Anthrax (cont.) Diagnosis based on identification of bacteria in sputum Early and aggressive treatment with antimicrobials necessary Anthrax vaccine available to military personnel, researchers, and health care workers dealing with anthrax patients 39 13
Influenza Sudden fever, pharyngitis, congestion, cough, myalgia Pathogens and virulence factors Influenza virus types A and B are the causative agents Hemagglutinin and neuraminidase mutations are responsible for production of new strains Mutations occur via two main processes» Antigenic drift» Antigenic shift 40 Flu Pandemic 1918-19 gym-hospital historical photo 41 Influenza budding, also shows H & N sites that make up H n N n numbering 42 14
How New Strains of Influenza Virus Occur 43 Influenza (cont.) Pathogenesis Symptoms of influenza are produced by the immune response to the virus Flu patients are susceptible to secondary bacterial infections due to virally produced damage to the lung epithelium Epidemiology Hard to calculate mortality articles place it between 3k and 49k influenza related deaths, depending Transmitted via inhalation of airborne viruses or by selfinoculation Complications occur most often in the elderly, children, and those with chronic diseases 44 Photo of Budding Virus, ready to shed 45 15
Influenza (cont.) Diagnosis, treatment, and prevention Signs and symptoms during a community-wide outbreak are often diagnostic Two drugs recommended to treat influenza Oseltamivir and zanamivir Treatment also involves supportive care to relieve symptoms Immunization with a multivalent vaccine 46 SARS Severe Acute Respiratory Syndrome SARS virus identified in 2003 Pneumonia leads to respiratory distress and potential death Corona virus family Droplet transmission 2-10 day incubation Symptoms: cough, breathing difficulty, >100.4F, chills, shaking, headache, aches Diagnostics: blood clotting tests, chest exam, Ab tests, PCR 47 SARS artificial color TEM 48 16
Respiratory Syncytial Virus Infection (RSV) Most common childhood respiratory disease Fever, runny nose, and coughing in babies or immunocompromised individuals Mild coldlike symptoms in older children and adults Pathogen Respiratory syncytial virus (RSV) Pathogenesis Formation of syncytia can help viruses evade the immune system and also infect new cells 49 Syncytium Formation in RSV Infected Cells 50 Respiratory Syncytial Virus Infection (RSV) (cont.) Epidemiology Transmission occurs via close contact with infected persons Diagnosis of RSV infection made by immunoassay combined with signs of respiratory distress Supportive treatment for young children Prevention includes aseptic technique of health care workers and day care employees 51 17
Hanta Virus sin nombre, 4 corners disease Hantavirus pulmonary syndrome; Hemorrhagic fever with renal syndrome Influenza-like, >50% mortality Not passed between humans Carried by rodents, shed in feces and urine Short incubation a few days Early symptoms can rapidly progress to death in a few days Chills, fever, aches No prevention or specific remedy, only support 52 One of the Hanta Virus carriers 53 Hanta Virus 54 18
Some other Viral Respiratory Diseases Other viruses that cause respiratory disease in children, the elderly, or immunocompromised individuals: Cytomegalovirus Metapneumovirus Estimated to be the second most common cause of viral respiratory disease behind rhinoviruses Parainfluenza viruses Three strains cause croup and viral pneumonia Occur primarily in young children 55 Fungal Infections can become systemic 56 Mycoses (fungal infection) of the Lower Respiratory System Examples 57 19
Some Mycoses of the Lower Respiratory System Coccidiodomycosis Resembles pneumonia or tuberculosis Infection can become systemic in immunocompromised persons Pathogen and virulence factors Caused by Coccidioides immitis Pathogen assumes yeast form at human body temperature Pathogenesis Enters the body through inhalation of arthroconidia from the soil 58 Coccidiodomycosis (cont.) Epidemiology Found almost exclusively in southwestern U.S. and northern Mexico Diagnosed by presence of spherules in clinical specimens Amphotericin B is the drug of choice for treatment Protective masks can prevent exposure to arthroconidia for those in occupations with high risk 59 Coccidiomycosis lesions in subcutaneous tissue 60 20
Coccidioides immitis in tissue characteristic spherules with spores 61 Flulike symptoms Blastomycosis Systemic infections can produce painless lesions on the face and upper body or purulent lesions on various organs Pathogen and virulence factors Caused by Blastomyces dermatitidis Pathogen assumes yeast form at human body temperature 62 Blastomycosis (cont.) Pathogenesis and epidemiology Enters the body through inhalation of dust carrying fungal spores Incidence increasing among immunocompromised Diagnosis based on identification of B. dermatitidis in clinical samples Treated with Amphotericin B Relapse common in AIDS patients 63 21
Cutaneous Blastomycosis disseminated from lung 64 Histoplasmosis (Histoplasma capsulatum) Most common human systemic fungal infection Dimorphic ascomycete (yeast at 37F), intracellular soil associated w/ bats, birds. Commonly asymptomatic or subclinical, some severe (~5%) cough w/ blood in sputum, skin lesions Inhalation leads to attack of alveolar macrophage. These disperse the infection. Often CMI (cellmediated immunity) rids the infection 65 Histoplasmosis progression 66 22
Pneumocystis Pneumonia (PCP) difficulty breathing, anemia, hypoxia, and fever Pathogen Pneuocystis jirovecii (pathogenic ascomycete) Pathogenesis and epidemiology Infection through inhalation of droplets containing the fungus Common disease in AIDS patients Treat with trimethoprim and sulfamethoxazole Impossible to prevent infection with P. jiroveci 67 Pneumocystis jirovecii Cysts lung 68 23