ࡱ> y{x` 3bjbj 7Z*$M$M$M$M,PMl]6MMMMMMMM=]?]?]?]?]?]?]$ _htac]-RMMRRc]MM]X[X[X[RMM=]X[R=]X[X[[{!]MM (71@$MW]=]]0]]bXb!]b!]M,NX[OvPMMMc]c]N[ MMM]RRRRD%`*"`* DISEASES of the RESPIRATORY TRACT Chapter 24 THE RESPIRATORY TRACT Major entry into body for M/Os UPPER RESPIRATORY TRACT (URT) Nose, pharynx, associated structures LOWER RESPIRATORY TRACT (LRT) Trachea, bronchi, alveoli of lungs DEFENSES: ciliated mucous membranes, alveolar macrophages, IgA antibodies BACTERIAL DISEASES of the URT Streptococcal Pharyngitis Scarlet Fever Diptheria Otitis Media STREPTOCOCCAL PHARYNGITIS Strep Throat Streptococcus pyogenes Group A b hemolytic Gram +ve coccus (80 serotypes) Also causes impetigo, erysipelas, acute bacterial endocarditis Symptoms very similar to viral pharyngitis Strep throat may lead to tonsillitis and/or otitis media, if untreated may lead to sequelae such as rheumatic fever & glomerulonephritis VIRULENCE FACTORS: M protein, streptokinase (lyses clots), streptolysins (lyses WBCs, RBCs & tissues) TRANSMISSION: respiratory route DIAGNOSIS: Culture of throat swab or quick agglutination test DOC: penicillin 2. SCARLET FEVER Streptococcus pyogenes - strains producing ERYTHROGENIC TOXIN Toxin due to prophage SYMPTOMS: reddish-pink skin rash due to hypersensitivity reaction & fever in response to the toxin Also see strawberry like spots on tongue TRANSMISSION: inhalation of infective droplets Occurs after a strep throat infection DOC: penicillin for pharyngitis 3. DIPHTHERIA (Respiratory Diphtheria) Corynebacterium diphtheriae Non-spore forming, Gram +ve pleomorphic rod TRANSMISSION: respiratory route Cells replicate in throat & secrete exotoxin into blood Prophage (lysogenic conversion) ( exotoxin that inhibits protein synthesis in vital organs SYMPTOMS: sore throat, fever, weakness Grayish, tough pseudomembrane covers throat Membrane contains M/Os, fibrin, dead tissue, WBCs May block air passage ---> suffocation PREVENTION: DPT vaccine (diphtheria toxoid) DOC: Penicillin & erythromycin plus DAT = diphtheria antitoxin to neutralize toxin 4. OTITIS MEDIA Infection of the middle ear Often after a cold or strep throat Or from contaminated water; eardrum injuries Streptococcus pneumoniae = most common cause Hemophilus influenze Moraxella catarrhalis Streptococcus pyogenes Staphylococcus aureus Seen primarily in younger children Pyogenic infections ( pressure on ear drum( ear ache DOC: amoxicillin in younger children VIRAL DISEASES of the URT Common cold Viral pneumonia 1. COMMON COLD Rhinoviruses (50%) Picornaviridae, non-enveloped ssRNA At least 113 serological types No practical vaccine, immunity is specific for a serotype Coronaviruses (15-20%) Coronaviridae, enveloped ssRNA DEFENSE: IgA antibodies TRANSMISSION: respiratory route and hand transmission. SYMPTOMS: sneezing, nasal discharge and congestion, cough. No treatment or vaccine available 2. VIRAL PNEUMONIA ADULTS: usually a complication of influenza, measles, chickenpox infection CHILDREN: often due to RSV = Respiratory Syncytial Virus BACTERIAL DISEASES of the LRT Pertussis Tuberculosis Bacterial pneumonia Legionellosis Psittacosis Q fever 1. PERTUSSIS (Whooping Cough) Bordetella pertussis Gram -ve coccobaccillus, encapsulated VERY CONTAGIOUS ~2000 cases/year in USA VIRULENCE FACTORS: PERTUSSIS TOXIN (exotoxin) - inhibits monocyte migration to infection TRACHEAL CYTOTOXIN (exotoxin) - inhibits action of cell cilia; kills ciliated epithelial cells, accumulation of mucus PILI - adherence to respiratory tract ENDOTOXIN 1. PERTUSSIS #2 TRANSMISSION: respiratory route CATARRHAL STAGE: initial stage Sneezing & coughing PAROXYSMAL STAGE:second stage Severe coughing ending in whooping sound as air is inspired Most contagious stage CONVALESCENCE STAGE: third stage Less severe coughing DOC: erythromycin DPT VACCINE: inactivated whole cell but a few side effects (including neurological damage) SUBUNIT VACCINE now being tested, acellular vaccine available for the 4th and 5th doses. 2. TUBERCULOSIS (TB) Mycobacterium tuberculosis Acid-fast, aerobic Gram +ve rod Grow very slowly (generation time ~ 20 h) Mycolic acids in cell wall = resist drying & disinfectants, confers acid fast property TRANSMISSION: inhalation ( lungs Phagocytosed by alveolar macrophages Killed and infection is cleared OR May live within macrophage & other macrophages are recruited to lungs, forms a caseous area Organisms can lie dormant in the center for years Lesions may heal and form calcified nodules called Ghon complexes. 2. TB #2 SYMPTOMS:fever, fatigue, coughing( hemoptysis), weight loss, weakness CONSUMPTION Chronic disease DOC: Streptomycin, INH (isoniazid), ethambutol, rifampin MUST BE CONTINUED for 1 to 2 YEARS DRUG RESISTANCE due to patients not taking medication as prescribed, give 2 or more drugs at the same time. PREVENTION: BCG vaccine = Bacillus Calmette-Guerin Avirulent strain of M. bovis Given to high risk people Not usually used in the USA Good CMI 2. TB: Disease Progression TUBERCLE = a small lump, characteristic of TB Bacteria, infected macrophages & neutrophils, early in the infection in the lung tissues Infected macrophages will die and release M/O Form a CASEOUS center (cottage cheese) Do not multiply but lie dormant for years Live bacteria within the center surrounded by tightly packed WBCs trying to wall-off M/O Eventually Calcium is deposited ---> see on X-ray Ghon complexes LIQUEFACTION: occurs when caseous center enlarges and M/O start to multiply Lesion may rupture allowing M/O to enter tissues & blood MILIARY TB: systemic M. tuberculosis infection, bones, skin, various organs. Mycobacterium bovis Cow pathogen can cause disease in humans Less than 1% of TB cases in USA TRANSMISSION: contaminated milk or food SYMPTOMS: affects primarily bones & lymphatic system TUBERCULIN SKIN TEST Testing for presence of CMI defense to M. tuberculosis M. tuberculosis - lives in macrophages Prevents fusion of phagosome with lysosome CD4+ TH1 cells activate macrophage by secreting cytokines Inject PPD under the skin ---> 48 hr later look for a delayed type hypersensitivity reaction Less than 5mm is negative, 5mm-10mm is intermediate, 10mm or greater is positive. TB: Epidemiology USA: 10 million+ people infected today 20,000 new cases/year Many are immigrants to USA Many are in AIDS patients 2,000 die/year M. avium & M. intracellulare (MAI) Leading cause of death in AIDS Found in birds & soil Enter via respiratory tract Malnutrition, overcrowding & stress promote TB 3. BACTERIAL PNEUMONIAS Inflammation of the lungs (bronchi & alveoli) Many etiologies: some bacteria, fungi, protozoa or viruses TYPICAL PNEUMONIAS: Streptococcus pneumoniae (Gram +ve diplococci), Sudden onset of shaking chills, chest pain, cough, and rusty sputum 23 different capsules make up vaccine ( subunit vaccine) Mainly affects elderly and people with lung disease DOC: Penicillin Hemophilus influenzae (Gram ve bacilli) OTHER: S. aureus, S. pyogenes, Moraxella catarrhalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Legionella pneumophilia (Legionnaires disease) ATYPICAL PNEUMONIAS: Mycoplasma - most common of this category, walking pneumonia DOC tetracycline & erythromycin Chlamydias 4. LEGIONELLOSIS Legionella pneumophila weakly Gram ve rod Strictly aerobic & fastidious nutritional requirements SYMPTOMS: high fever, non-productive cough, chest and abdominal pain, diarrhea TRANMISSION: seems to be transmitted from contaminated air NOT person-person Air conditioners, cooling towers, water lines (produce sprayers) Especially affects older (50+ years) that are heavy smokers or an underlying lung disorder DOC: erythromycin and rifampin 5. PSITTACOSIS Chlamydia psittaci: Gram +ve intracellular rod Causes a pneumonia Parrot fever respiratory disease associated with psittacine birds (parrots and parakeets) Ornithosis disease found in other (non-psittacine) birds TRANSMISSION: Contact and inhalation Person to person transmission has occurred Contaminated bird droppings & mucopurulent nasal secretions DOC: tetracycline 6. Q FEVER Coxiella burnetii rickettsia Queensland 1st described in Queensland, Australia SYMPTOMS: Long lasting fever, chills, headache & pneumonia-like symptoms TRANSMISSION: respiratory route or by ingestion of contaminated milk Appears to be only rickettsia that does not require a vector for transmission Can survive long periods outside cells: two forms Large cell less peptidoglycan and no cross-links Recently an endospore-like structure has been identified that forms at one end of the large cell form = resistance? Small cell recently divided cell form VIRAL DISEASES of the LRT Influenza Hantavirus Pneumonia SARS 1. INFLUENZA (Flu) Influenza virus: Orthomyxoviridae: enveloped, ssRNA Types A, B and C Type A is most common Segmented genome (8 helical nucleocapsids) Each codes for different proteins Envelope has 2 different types of peplomers PEPLOMERS (protein spikes) are antigenic H = hemagglutinin - attachment Four different H (H0, H1, H2, H3) N = neuraminidase - release from host cell Two different N (N1, N2) Different antigenic types of H & N from genetic changes SYMPTOMS: incubation 24 - 48 hours Chills, fever, muscle pain, headache 1. INFLUENZA #2 GENETIC CHANGES: ANTIGENIC DRIFT = minor changes due to point mutations in RNA segment that codes for H or N peplomer ANTIGENIC SHIFT = major changes due to genetic reassortment as a result of 2 different viruses infect same cell ( replicate and reassort RNA segments during assembly of viral particle Genetically different peplomers are not neutralized by Ab to previous viruses REASSORTMENT can occur in other animals, ducks, pigs, horses etc. Swine flu 1. INFLUENZA: Epidemiology Endemic in USA now Epidemics every 2-5 years Pandemics ~ every 10 years Due to changes in the viral peplomers People have no immunity to new virus National vaccination program started HSW1N1 = virus responsible for 1918 pandemic Possible H5N1 pandemic MAJOR FLU EPIDEMICS: 1918 HSW1N1 1929 H0N1 1947 H1N1 1957 H2N2 Asian Flu 1968 H3N2 Hong Kong Flu 1976 -Ft. Dix, NJ - 500 soldiers had flu caused by HSW1N1 - 1 died 1. INFLUENZA #3 PREVENTION: VACCINE Killed viral vaccine Multivalent - effective against more than one type of virus Must change as new viruses emerge High risk people - elderly Effective ~ 3 years 2. HANTA VIRUS PNEUMONIA Bunyavirus - enveloped, helical RNA 1993: Navajo Indians in SW USA 25 died TRANSMISSION: urine of infected rodents, people inhale virus SYMPTOMS: severe respiratory disease Internal hemorrhaging ---> drowning DOC: primarily supportive measures SARS Severe Acute Respiratory Syndrome Caused by a Wild type Coronavirus Outbreak initiated in south china and moved globally around the world Possible close contact of wild animals and humans in markets, created a more virulent strain of the virus Symptoms: high fever, headache, body aches, dry cough, and pneumonia. Transmission is by respiratory route from person to person. 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