Diseases of the Respiratory System(1).pdf

Diseases of the Respiratory System Bacterial Diseases The Upper Respiratory Tract Lower Respiratory Tract credit: modification of micrograph provided by the Regents of University of Michigan Medical School © 2012 Innate Defenses and Microflora Upper...

Diseases of the Respiratory System Bacterial Diseases The Upper Respiratory Tract Lower Respiratory Tract credit: modification of micrograph provided by the Regents of University of Michigan Medical School © 2012 Innate Defenses and Microflora Upper Respiratory: Mucocilliary Escalator Smoking will inhibit Mucus Tonsils Patrolling Phagocytes Streptococcus spp. Staphylococcus spp. Klebsiella pneumoniae, Haemophilus influenzae Lower Respiratory: Epiglottis Mucus Coughing Narrow Pathways Alveolar Macrophages Some bacteria infect Healthy lungs are sterile Need free surfaces for efficient gas exchange Bacterial Diseases of the Respiratory System PART ONE: Upper Respiratory System Group A Streptococci Diphtheria Laryngitis, sinusitis and bronchitis Otitis Media Pertussis Lower Respiratory System Tuberculosis Bacterial Pneumonias Legionnaire’s Disease Atypical Infections Streptococcal Pharyngitis Most common in children 5-15 years old Inflammation of throat, adenoids, & lymph nodes of the neck Tonsils develop pus filled lesions Causative agent: Streptococcus pyogenes Group A beta hemolytic Asymptomatic individuals may be carriers credit: modification of work by U.S. Centers for Disease Control and Prevention - Medical Illustrator Streptococcus pyogenes Group A: classification based on a cell wall carbohydrate, C substance, also known as Lancefield antigen. Also classified based on the presence of M protein, a virulence factor in Group A streptococci. Over 80 types of M protein that inhibit complement & phagocytosis. Many streptococci produce streptolysin O which destroys RBC and WBC. Also produce Erythrogenic toxin that damages blood vessels, leading to a red skin rash. Streptococcal Pharyngitis Transmission: direct contact, droplets, fomites Incubation: 1-3 days Signs/Symptoms: sore throat, red tonsils, coughing, sneezing, high fever, & swollen lymph nodes Treatment: Penicillin/Amoxicillin Prevention: Hand washing Persons with sore throat should be seen by a doctor for tests to find out whether they have strep throat. CDC If they do, the person should stay home until 24 hours after taking an antibiotic. Scarlet Fever aka Scarlatina A rash plus strep throat. Erythrogenic toxin Usually seen in children under the age of 18. Causative Agent: Streptococcus pyogenes Transmission: mouth & nasal fluids, fomites Today: Not as severe an illness Rarely complicated Scarlet Fever Signs/Symptoms tiny red bumps on the chest and abdomen. Spreads all over the body, like a sunburn Feels like a rough piece of sandpaper. 2-5 days then peeling The throat is very red & sore with white or yellow patches. A fever of 101°F with chills is common. Strawberry tongue Diagnosis: throat culture Treatment: penicillin By SyntGrisha - Own work, CC BY-SA 4.0 Complications of GAS Infections Glomerulonephritis Inflammation of glomeruli (kidney) Signs and symptoms Less frequent urination Cola- or tea-colored urine (blood in urine) Foamy urine (protein in urine) High blood pressure Fluid retention in the face, hands, feet & abdomen, Fatigue from anemia Kidney failure Complications of GAS Infections Rheumatic fever a serious inflammatory condition that can affect the heart, joints, nervous system and skin. Most common in 6-15 year olds Rare Even in untreated cases, only about 3 % of cases lead to rheumatic fever. Not as common in the US today due to widespread penicillin use. Still common in developing countries. GAS Complication: Rheumatic Fever Signs/Symptoms appear within 5 weeks of an untreated strep throat. painful, swollen joints, chest pain, fatigue and shortness of breath In more than 1/2 of all cases, rheumatic fever affects heart valves & interferes with blood flow through the heart. Diagnosis: Electrocardiogram or a Chest X-ray Prevention: prompt and thorough treatment of a strep throat infections. Other Complications of GAS Infections PANDAS: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections Necrotizing Fasciitis & Streptococcal Toxic Shock Syndrome (STSS) Two of the most severe, but least common, forms of invasive group A Streptococcal disease Necrotizing fasciitis About 20% of patients with necrotizing fasciitis die. STSS: fever, dizziness, confusion, & a flat red rash over large areas of the body Diseases of the Upper Respiratory Tract- Laryngitis, Epiglottitis, & Sinusitis Causative Agent: S. pneumoniae or H. influenzae Transmission: droplets Signs and symptoms: Congestion that makes breathing though nose difficult Sore throat Pain, tenderness and swelling around sinuses Headache Fever Reduced sense of smell or taste Cough Tooth pain, bad breath Fatigue Treatment: Time Ear Infections (Otitis Media) One of the most common illnesses affecting infants & young children. 3 out of 4 American children have had at least one ear infection by age 3. Ear infections usually start with a cold, which can cause fluid to build up behind the eardrum. The fluid itself isn't necessarily a problem. Causative Agents: Streptococcus pneumoniae, Streptococcus pyogenes, & Haemophilus influenzae (non-encapsulated) account for about half of the cases. Pneumococcal and HiB vaccines provide some protection Otitis Media A child's Eustachian tubes are usually narrower & shorter than are those of an adult. This increases the likelihood that inflammation will block the tubes completely, trapping fluid in the middle ear. Fluid buildup will temporarily affect child's hearing. Signs/Symptoms pain, fever, irritability or listlessness & difficulty sleeping Diagnosis: redness of the ear canal of the eardrum & for evidence of fluid behind the eardrum. Otitis Media- Treatment Penicillin/Amoxicillin Myringotomy Drainage tube Recurrent infections only modification of work by “DrER.tv”/YouTube modification of work by Li Mg, Hotez PJ, Vrabec JT, Donovan DT 1925, Nome, Alaska 2 children have died, and others are presenting with a thin membrane on the backs of their throats Death has been by suffocation By :Dileepunnikri - Own work, CC BY-SA 3.0, Corynebacterium diphtheriae Gram positive, club shaped bacilli with metachromatic granules. Granules are phosphate inclusions Bacteria remain close to one another when they divide and form a picket fence arrangement known as a palisade layer Toxin-producing strains of Corynebacterium diphtheriae Transmission: respiratory CDC droplets Diphtheria Signs/Symptoms: Exotoxin: Protein synthesis inhibitor in epithelium Dead tissue & WBC accumulate → pseudomembrane Sore throat The pseudomembrane causes respiratory blockage & death may occur, especially in children In adults, toxin spreads thru blood causing heart damage and nerve sheath damage Treatment: penicillin or erythromycin Prevention: DPT- diphtheria, pertussis, & tetanus toxoids DTaP: Diphtheria, tetanus and Acellular pertussis vaccine 100 Day Cough A patient reports that a cold has been going through the family, but the newest member, a five week old girl appears to have been hit the hardest. Everyone has runny noses and is coughing quite a bit The infant is coughing, lethargic and in distress The coughing fits have become violent and the child is occasionally cyanotic, and has emesis. A distinct gasp is heard after the fits The child lives with her parents and elderly grandparents https://youtu.be/8QWdEwjBEBw Pertussis (Whooping Cough) A highly contagious disease known only in humans 80-100% chance of transmission This disease results in high morbidity and mortality in many countries every year. Mostly infants too young to be vaccinated In the United States, 5000-7000 cases are reported each year with incidence of pertussis increasing steadily since the 1980s. Causative agent: Bordetella pertussis Gram-negative coccobacillus Transmission: Droplets Pertussis Incubation: 7 days Signs/Symptoms: There is no invasion of tissue but ciliated cells are killed or their action is impeded. This leads to mucus accumulation Mediated by toxins (tracheal cytotoxin and pertussis toxin) TCT destroys ciliated epithelium: specialized endotoxin PtxAB causes systemic effects; disrupts cell processes of phagocytes The disease progresses through three stages: Fever, sneezing, vomiting, and a mild, dry persistent cough: catarrhal stage Mucus and bacteria fill the airways, immobilize the cilia, & there is a strong violent cough: paroxysmal stage 1-6 weeks later, secondary infections are common: convalescent stage Pertussis Diagnosis: culturing of posterior pharyngeal wall Treatment: Penicillin & Erythromycin, prior to respiratory blockage Must be given in the earliest stages of disease to be effective Prevention: DTaP Recommended for caregivers to infants, the elderly, and pregnant women in their third trimester Complications: hypoxia, apnea, pneumonia, seizures, & encephalopathy 50% of infants with Pertussis will require hospitalization Pertussis Cases are Going Up Why? A patient comes in with a cough… What microbes might be responsible? What else do you need to know? Bacterial Diseases of the Lower Respiratory System Tuberculosis Bacterial Pneumonias Legionnaire’s Disease Atypical Infections Tuberculosis From 1600-1900’s accounted for 20-30% of all deaths worldwide Strong natural selection for TB survival Incidence is rising 90% of people infected with TB will clear the infection without knowledge of being infected Lübeck 1926 249 babies accidentally vaccinated with virulent bacteria 76 deaths, but the rest did not become ill By CDC/Dr. George P. Kubica (phil.cdc.gov CDC-PHIL ID #5789) [Public domain], via Wikimedia Commons Mycobacterium Tuberculosis Acid Fast Rod; Obligate Aerobe, Mycolic acid Slow growing in culture (20-hour doubling time) Can survive for months in dried sputum Mode of transmission: Airborne or Droplet Only 1-3 bacteria make it to the lower lung Alveolar macrophages ingest the bacteria Sometimes the macrophages become activated and destroy the bacteria Sometimes not… Pathogenesis of TB Bacteria multiply within macrophages and neutrophils Cells rupture and an inflammatory response results Chronic granulomas or tubercles result Walled off area with caseous interior (cheesy) Lesions heal and become calcified Or they burst → pneumonia Good cell mediated immunity necessary for defeat. Why? Bacteria can cause latent infection credit: modification of work by Centers for Disease Control and Prevention Active Tuberculosis Signs and Symptoms Coughing for 3 weeks or more Eventually with blood in sputum Weight loss Fever Chills Night Sweats Anorexia Weakness Only contagious during active disease  Treatment, Prevention and Testing Treatment Isoniazid and/or rifampin for 1 year MDR and XDR strains exist Fluorquinolones (MDR) Pretomanid, Bedaquiline and Linezolid (XDR) Testing Tuberculin or PPD Measures immune response to protein Not always indicative of disease Prevention Isolation BCG Only in very high risk populations in US Renders PPD testing useless Effectiveness approaches 0 in adolescents and adults Very effective in children CDC  Bacterial Pneumonias Pneumonia: Inflamed alveoli in one or both lungs, may also have pus or fluid, and cause difficulty breathing, fever and chills Classified by: Site: Single or double lobe, or bronchial Lobar forms are often accompanied by pleurisy Inflammation of the pleural membranes causing painful breathing Pennsylvania 1976 A convention for members of the American Legion 221 patients report to the hospital over 2-10 days 36 die, mostly elderly Pneumonia is the cause of death A never before isolated Gram negative rod found Filters from the hotel sauna and AC ventilation reveal the presence of the same Gram negative rod Legionella pneumophila Legionnaire’s Disease Fatality 5-30% of symptomatic cases Bronx Opera House 2015: 133 cases 16 dead All deceased were adults with underlying health conditions Transmission: Mists from a contaminated water source Not communicable Grows within amoebae Signs and Symptoms: High fever, chills, cough (orange sputum), diarrhea, muscle aches, tiredness Many people are infected but asymptomatic Diagnosis: DNA probe test or Fluorescent Antibody testing Treatment: Erythromycin and other macrolides Prevention: Water sanitation through copper-silver ionization CDC Pneumococcal Pneumonia 80% of Bacterial Pneumonias Organisms colonize the upper respiratory tract and then travel lower Streptococcus pneumoniae (G+ diplococci) 90 different serotypes, most dangerous for the elderly Most individuals are resistant to disease and colonized with S. pneumoniae Transmission, Signs and Symptoms Droplet and person-to-person High fever Chest pain Labored breathing Rust colored sputum Treatment: Penicillin, Erythromycin, and tetracycline Vaccine is available to 23 of the 90 serotypes CDC Other Bacterial Pneumonias Mycoplasma pneumoniae (Primary Klebsiella pneumoniae Atypical Pneumonia: PAP) G- encapsulated rod: gel-like sputum Largest cause of pneumonia in ages 5-19 Droplet transmission Common in institutional settings Nosocomial: Immunocompromised 10% mild and no respiratory signs Cephalosporin treatment Haemophilus influenzae G- coccobacilli Serratia marcescens Similar to pneumococcal in signs and G – rod symptoms and transmission Nosocomial: opportunistic Purulent sputum Commonly antibiotic resistant Second generation cephalosporins (acquisition of R plasmids) Occurs in immunocompromised patients and chronic alcoholics Vaccine Available Mycoplasma pneumoniae The micrograph shows Mycoplasma pneumoniae using their specialized receptors to attach to epithelial cells in the trachea of an infected hamster. (credit: modification of work by American Society for Microbiology) Psittacosis/Ornithosis Since 1996, less than 50 confirmed cases were reported in the US each year. It affects bird owners, pet shop employees, veterinarians and employees of poultry-processing plants. Causative agent : Chlamydia psittaci Transmission: direct contact with nasal droplets & feces of infected birds. Pneumonia Rarely fatal with prompt treatment → Tetracyclines No treatment →20% fatal Bird quarantine for 30 days Viral Diseases of the Respiratory System The Common Cold Influenza Viral pneumonia (Respiratory Syncytial Virus) Hanta Virus Pulmonary Syndrome Common Cold Most people get 3-4 colds per year Not life threatening, but largest burden of disease Cause: More than 200 viruses Rhinovirus (30-50%) Coronaviruses (10-15%) 20-30% ????? Incubation: 2-4 days Transmission: Droplet, direct contact or fomites Symptoms: Let’s list some! Common Cold Treatment: Time, Symptomatic “With treatment colds will get better in a week, without treatment…seven days.” Prevention: No Vaccine Hand washing Sneeze Hygiene Complications: Secondary Bacterial Infections Why does a cold spread so widely? Balanced pathogenesis Influenza The last great plague In U.S. 5-20% of people get the flu every year 200,000 will be hospitalized 36,000 will die Etiology: Influenzavirus 8 strands of RNA in a capsid, surrounded by an envelope Envelope contains two major proteins Neuraminidase → Help the virus separate during shedding Hemagglutinin → Attach to cells for infection → Highly antigenic credit: modification of work by Dan Higgins, Centers for Disease Control and Prevention Influenza Transmission: Complications: Droplet, fomite Bacterial pneumonia Can be a zoonosis from other mammals Dehydration Pigs, fowl Worsening of chronic medical conditions Contagious from -1 to 7 days after the Sinus and ear infections onset of symptoms Very young, very old, and pregnant Symptoms and Signs: women are most at risk from Sudden high fever complications. Headache Exhaustion Dry cough Sore throat Nasal congestion Muscle aches  Prevention and Treatment Prevention: Flu vaccination Every year…Why? NO EXCUSES Egg allergy no longer a contraindication for some formulations. Cell culture instead of eggs: Flucelvax and Flublok Treatment: Supportive and symptomatic Medications (must be started within 48 hours of symptoms) Polymerase Acidic Endonuclease Inhibitors (2018) Required for viral replication within the cell Xofluza 1 pill treatment Neuraminidase Inhibitors Tamiflu and Relenza Blocks action of enzyme that allows flu virus release Amantadines Lots of resistance around Blocks a protein channel that the virus uses to un-coat itself Influenzavirus: Evolution Antigenic drift: Influenza is an RNA virus → replication is more error prone than DNA viruses Mutations in HA allow the virus to escape previously made antibodies Evolution is more towards increased transmission and lower virulence Patient can walk around and spread it easily Antigenic shift: Co-infection of a single cell with two or more viruses at once 8 segments of viral RNA get reassorted and shuffled to make a completely different virus Commonly occurs when humans, fowl and pigs live in close proximity to one another No previous immunity in the population Can cause pandemics of high transmissibility and virulence…or not. SARS-CoV-2: Cause of CoViD-19 + sense RNA, non-segmented genome of about 30Kb Club like spikes protruding from the envelope give a “crown”-like appearance Uses ACE2 receptor for entry into respiratory and gastrointestinal cells Uses + strand RNA to make its RNA- dependent RNA polymerase complex Current worldwide pandemic Pandemic → widespread and sustained transmission of an infectious disease By https://www.scientificanimations.com - https://www.scientificanimations.com/wiki- images/, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=86436446 CoViD-19 Currently no approved Possible Treatments: None treatment currently proven or approved Clinical picture is unclear Remdesivir Fever Famotidine Cough Hydroxychloroquine/azithromycin Clotting Issues Skin Rashes Vaccine Development Viral Pneumonia: RSV Etiology: Respiratory Syncytial Virus (RSV) Transmission: Respiratory Secretions, Close contact, Fomites Signs and Symptoms Fever, runny nose, cough and wheezing Hypoxia Infants most at risk Most children recover in 8-15 days Treatment: Supportive and Symptomatic Severe disease can result in a need for mechanical ventilation and oxygen Immunoglobulin and Ribavirin Hanta Virus Pulmonary Disease Rare: 637 cases in the US → ever Recent outbreaks: Montauk, LI Yosemite National Park 60% Fatality rate Hanta Virus Pulmonary Disease Transmission: Urine, droppings, & saliva of deer mice become aerosolized Not communicable from person to person Risk Groups: Homes, cabins, sheds, & outbuildings, including barns, garages and storage facilities infested with rodents Incubation: Not positively known but believed to be 1 - 5 weeks after exposure Hanta Virus Pulmonary Disease Signs/Symptoms: Fatigue Fever Muscle aches especially in the large muscle Headaches Dizziness Chills Abdominal problems, such as nausea, vomiting, diarrhea, & abdominal pain Hemorrhage in kidneys (Classic) or lungs (Sin-Nombre; U.S.) Treatment: oxygen therapy, ribaravin Prevention: Eliminate or minimize contact with rodents in your home, workplace, or campsite. Fungal Diseases of the Respiratory System Pneumocystis carinii pneumonia (PCP) Histoplasmosis Cryptococcosis Pneumocystis Pneumonia (PCP) Causative agent: Pneumocystis carinii jiroveci Invades cells of the lungs causing alveolar septa to thicken & the epithelium to rupture. This results in a foamy exudate collecting in the alveoli. Fungus can spread to other organs and cause extra- pulmonary infections CDC Pneumocystis carinii Pneumonia (PCP) Occurs in infants, elderly & immunocompromised individuals 80% of AIDS patients get PCP, cancer patients, organ transplant patients Transmission: not known Signs/Symptoms: difficulty breathing, nonproductive cough, fever & fluid in the lungs observed in a chest X ray Diagnosis: microbe in sputum or in biopsied tissue Treatment: Trimethoprim/ Sulfamethoxazole is the drug of choice. Histoplasmosis Causative agent: Histoplasma capsulatum The fungus has been found in poultry house litter, caves, areas harboring bats, & in bird roosts. Risk Groups: Infants, young children Older persons, in particular those with chronic lung disease. Disseminated disease is more frequently seen as an opportunistic infection in people with cancer or AIDS. Transmission: Inhalation of spores (no person to person transmission) Modification of work by Centers for Disease Control and Prevention. Openstax.org Histoplasmosis Incubation: 3 to 17 days Signs/Symptoms: Most infected persons have few Malaise, fever, chest pains, & a dry or nonproductive cough Diagnosis: Chest X ray (has a distinctive pattern) or positive histoplasmin skin tests Treatment: Amphotericin B & ketoconazole Modification of work by Centers for Disease Control and Prevention. Openstax.org Cryptococcosis Causative agent: Filobasidiella (formerly Cryptococcus) neoformans, an encapsulated yeast Transmission: Inhalation of spores from the bird droppings, particularly pigeons in urban areas, & soil. 0.4-1.3 cases per 100,000 in the general population. In the United States, 85% of cases occur in HIV-infected persons. Among persons with AIDS, the annual incidence is 2-7 cases per 1,000 After spores are inhaled, they travel to the brain via the blood. CDC Cryptococcosis Signs/Symptoms: Initial pulmonary infection is usually asymptomatic. Most patients present the disseminated infection, especially meningoencephalitis with a headache, nausea, confusion, staggering and fever. Meningitis may lead to permanent neurologic damage. Treatment: Amphotericin B Prevention: reducing pigeon populations & decontaminating droppings with alkali