LS Elementary Public Health
LS Elementary Public Health MICR 1153
Weber State University
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Popular in Microbiology
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Date Created: 10/28/15
I Introduction A Importance of disease 1 2 3 historical a cholera pandemic after each hajj Moslem pilgrimage b crusaders brought back cholera and leprosy 1100 1300 c plague 20 of European population died 1300 d syphilis brought back by Columbus spread around world by other explorers 2 Charles VII of France died of syphilis all heirs born dead of syphilis end of dynasty 3 almost 80000 Union soldiers during CivilWar 3 million during WWI 1 million during WWII economic culturalsocial A H v B Briefhistory of disease in the US 1 759 5 top 10 causes ofdeath a shift from infectious to chronic disease b public health guidelines including better sanitation and personal hygiene are responsible for the increased life spans and overall better health we have today c lifestyle less harm il diseases most common diseases severity vs quotequency emerging diseases pro blems Darwinian medicine 11 Principles of Disease Occurrence A Theories of disease causation 1 2 B Terminology 1 germ theory a infectious disease is caused by the transfer of infectious agents b didn t explain why some people got sick but others didn t multiple causation Box 21 a several factors contribute to development of disease 1 disease agents 2 host factors 3 environment b accounts for noninfectious diseases too morbidity rate time mortality rate incidence rate a number of new cases occurring during a speci c time b number of new cases divided by population at risk x 1000 number of ill people per susceptible population during a speci c number of deaths per total number of disease cases C Levels of prevention 1 primary prevention measures taken before disease occurs to reduce susceptibility 2 3 1 2 1 2 secondary prevention diagnosis of disease already present tertiary prevention treatment of disease return ho st to normal health D Disease agents for infectious disease viruses acellular protein coat around genetic material a b a b a c protozoa a b metazoa a b a b 1 2 DNA or RNA as genetic material single or double stranded obligate parasites bacteria Table 22 prokaryotic no membranebound organelles normal ora helps protect against infection fungi eukaryotic secrete hydrolytic enzymes breaks down tissues diseases can arise if antibiotics alter bacterial normal ora animallike eukaryotes release toxins and enzymes tapeworms roundworms ukes can migrate throughout the body 111 The History of Infectious Disease A Birth of modem microbiology Robert Hooke first person to see cells but not bacteria with a microscope 1665 microorganisms rst observed and described by Antony van Leeuwenhoek 1676 simple single lens micro scopes 50 300x magni cation huge curiosity observed anything he could A H v 2 3 4 5 6 7 animalcules intestinal organisms including Giardia bacteria quotom overnight pepper infusions seeds and plant embryos small invertebrates spermatozoa red bloo d cells essentially all main unicellular organisms we know today a yeasts b protozoa c algae d bacteria quot1 have had several gentlewomen in my house who were keen on seeing the little eels in vinegar but some of them were so disgusted at the spectacle that they vowed they39d never use vinegar again But what if one should tell such people in the lture that there are more animals living in the scum on the teeth in a man39s mouth than there are in a whole kingdomquot superior observation skills but did not allow others to copy his techniques and verify his results 3 Edward Jenner observed that milkmaids didn t get smallpox 1800 a prior exposure to cowpox seemed to protect against smallpox b began inoculation with cowpox c Pasteur continued work along this line with vaccines against anthrax and rabies 4 Ignaz Semmelweiss irrproved hospital sanitary practices a observed mortality rates lower with midwives than doctors 1 strep infection child bed fever or puerperal sepsis 2 got fired b iend died ofP S quotom cut during autopsy ofPS victim c hypothe sized an invisible agent responsible for disease d sanitized hospitals by required handwashing and changing lab coats red again e died in insane asylum of PS 5 Pasteur termed the microbial spoilage of wine and beer quotdiseasesquot a considered that microorganisms could act as agents of infectious disease 1 already known that fungi could cause disease in wheat and rye 2 a mgus was responsible for the great Potato B light of Ireland b observed foreign organisms bacteria in contaminated wine 6 John List er sterilized instruments with heat and used phenol on dressings and sometimes on wounds 1 phenol kills bacteria 2 less wounds became infected 3 indirect evidence for role of bacteria in infection 7 Direct evidence for role of bacteria in disease was by Robert Koch working with anthrax 1 injected a series of 20 healthy mice with anthrax bacilli 2 inoculated broth with spleen from infected mouse isolated anthrax bacilli spores injection of spores into mice resulted in anthrax 8 Koch39s Postulates a The organism should be present in every use of the disease but absent in healthy individuals b The suspected microorganism must be isolated and gown in pure culture c The disease must result when the isolated microorganism is inoculated into a healthy host d The same microorganism must be isolated again from the diseased host Vaccination developed by Pasteur working with chickens and cholera 10 The germ theory of disease from Pasteur s and Koch s workdescribes the demonstration that microbes can be the agents of disease a generalbelief was that epidemics were penalties of God b greatest impetus for development of microbiology c contagious diseases spreadthrough populations by contagions d after discovery of microbe s contagions microorganisms B Principles of microbial disease 1 most important technological application of microbiology is medical AA gm vv F impetus for development of microbiology microbes cause disease in man animals plants and each other c not the only cause of disease 1 schisto somia sis 2 lung cancer 3 hemophilia or sickle cell anemia 2 disease is a form of parasitism host supplies food 3 disease occurs when a microbe infects a host to which it is imper ctly adapted but can grow and ourish a biological defense processes brought into play b if defenses overstrained or unsucces S ll host sickens and may die 1 if host dies parasite dies 2 welladapted parasites cause little or no damage 3 poorlyadapted or inadvertent parasites are dangerous and sometimes lethal 4 humans and other higher organisms have developed a balanced microbial ora as bacteria are passed around between community members a newborns are almost sterile carrying inside and out bacteria derived from the mot her39s vagina 1 soon pick up lactobacilli 2 gradually develops the adult population of mixed microbes 5 normal equilibrium can be upset by travel to another area country and exposure to new strains of bacteria C pathology scientific study of disease 1 etiology the cause of disease 2 pathogenesis manner in which a disease develops 3 structure and functional changes brought about by disease and its final effects on the body 4 infection invasion or colonization of the body by pathogens a normal ora can be present in abnormal area e g E 001139 OK in intestine pathogenic in urinary tract b most microbes are nonpathogenic 5 disease result of an infection that changes the state of health a abnormal state in which part or all of the body is not properly adjusted or carrying out normal mctions b infections can exist Without disease eg HIV 6 normal ora a animals are germfree in utero b microbial populations begin to establish themselves at birth c estimated 1013 body cells and 1014 bacterial cells d normal ora microorganisms that colonize the body but do not produce disease under normal conditions e transient ora microorganisms that are present for brief periods days months and then disappear 7 symbiosis living together 9 D 8 9 a commensalism one organism bene ts the other is unaffected 1 many if not most of normal ora 2 especially common relationship on extemal skin b mutualism both organisms bene t 1 common with intestinal bacteria 2 E 001139 gets nutrients in large intestine produces vitamin K and B vitamins c parasitism one bene ts the other is harmed typical pathogenic relationship opportunists potentially pathogenic organisms that do not ordinarily cause disease in their normal habitat ina healthy person a organisms that gain entrance to the bloodstream through broken skin b compromised hosts are subject to diseases caused by normal ora c often normal ora includes pathogens kept in check for determination of the etiological agent recall Koch39s postulates a The organism should be present in every case of the disease but absent in healthy individuals b The suspected microorganism must be isolated and gown in pure culture c The disease must result when the isolated microorganism is inoculated into a healthy host d The same microorganism must be isolated again from the diseased host 10 some exceptions where causative agent cannot be identi ed using Koch39s postulates a T reponema pallidum the causative agent of syphilis has never been cultured on arti cial medium b Mycobacterium leprae the causative agent of leprosy has never been cultured on arti cial medium c alternative steps 2m be used to modify Koch39s postulates for example inoculating test organisms with infected tissue instead of isolated micro organisms classi cation of infectious diseases 1 5 symptoms changes in body mction a eg pain and malaise b often subjective not apparent to an observer signs objective changes that can be observed and measured by a physician a lesions changes in tissue caused by disease swelling fever paralysis b syndrome speci c group of synptoms that always accompany a particular disease communicable able to spread directly or indirectly om one host to another chicken pox measles herpes tuberculosis a contagious easily communicable chicken pox measles b noncommunicable not spread from one host to another tetanus infection can be localized invading MO limited to relatively small body area or systemic generalized spread throughout the body a localized boils or abscesses b systemic measles reservoir of infection source of disease organisms 9 a human body is primary reservoir 1 carriers harbor and transmit pathogens Without exhibiting illness themselves 2 latent diseases an be spread during incubation period before symptoms appear or during the convalescent period during recovery b animal reservoirs 1 zoonoses diseases that occur primarily in animals but can be transmitted to humans 2 rabies mammals Rocky Mountain spotted fever ticks c nonliving reservoirs 1 soil and water 2 soil has low levels of pathogens under normal conditions 3 pathogens often introduced to water or soil by humans eg fecal contamination disease transmission has three principle routes a contact transmission spread of agent by direct contact person to person transmission 1 respiratory diseases measles smallpox STDs 2 can also be by indirect contact a indirect contact transmission relies on inanimate objects handkerchiefs eating utensils b droplet transmission discharged mucous droplets that only travel short distances sneezing coughing laughing b vehicle transmission agents like water food air c vectors animals that carry pathogens from host to host 1 insects arthropods most common 2 transmission can be passive surface transfer or active transmitted through bites nosocomial infections acquired as a result of a hospital stay a MO in hospital environments and compromised hosts 1 gram positive cocci Staphylococcus aureus used to be most common 2 major causes today are gram negatives E coli and Pseudomonas aeruginosa especially antibioticresistant strains b compromised host resistance to infection inpaired by disease therapy or bums 1 broken skin or mucous membranes remove protective barrier 2 suppressed immune system c controlled by scrupulous cleaning and disinfection pathogenicity ability of a pathogen to produce a disease by overcoming host defenses Virulence the degree of pathogenicity E Mechanisms of pathogenicity 1 portal of entry how pathogen gains access to the body a mucous membranes 1 respiratory gastrointestinal genitourinary tracts conjunctiva membrane around eyeball 2 gastrointestinal and respiratory tracts most common b skin 1 usually a defense against disease 2 microbes gain entrance through openings a sweat gland ducts b hair follicles c parenteral route direct deposition into tissues beneath skin or mucous membranes 1 wounds 2 bites d use of preferred portal of entry often prerequisite to ability to cause disease 1 ingested Salmonella typhi preferred portal produce typhoid fever but no reaction when rubbed on skin inhaled streptococci can cause pneumonia but if swallow ed usually no signs or symptoms dose number of invading cells inportant as defense mechanisms will eliminate man adherence attachment to host tissues a essential for most pathogens to result in pathog enicity b surface molecules ligands or adhesins often located on glycocalyx or fimbrae bind to host receptors 1 most adhesins are glycoprote ins or lipoproteins 2 most receptors are sugars mannose Penetration of host defenses a capsules 1 protects cells against phagocytosis a phagocytosis process where certain body cells engulf and destroy microbes b in second line of defense human body produces antibodies against the capsule which when on the capsule surface allow phago cyto sis to occur 2 common with pneumoniacausing organisms Streptococcus pneumoniae Klebsiella pneumoniae Hemophilus in uenzae b cell wall components 1 Mycobacterium tuberculosis has a waxy cell wall that resists digestion by phaogcytes 2 Streptococcus pyogenes has a heat and acidresist ant M protein a aids attachment b resists phagocyto sis 2 v enzymes a extracellular enzymes that break cells open dissolve materials between cells form or dissolve blood clots and other mctions b leukocins destroy neutrophils white blood cells and macrophages c hemo lysins lyse red blood cells f g h coagulases clot blood may protect bacteria several enzymes that enhance spread quotom a focal infection 1 kinases dissolve blood clots formed to isolate infection 2 hyaluronidase breaks down connective tissue allowing cells to spread 3 collagenase hydrolyzes connective tissue necr otizing factors kill cells hypothermic factors lower body temperature proteases break down tissues damage me chanisms a three basic ways for success il invaders to damage ho st cells 1 direct damage in immediate vicinity of invasion 2 toxin production transported by uids to damage distant sites 3 induction of hyperse nsitivity reactions host cells destroyed when pathogens metabolize and multiply inside the host cells toxins poisonous substances produced by specific MO 1 usually the primary mechanism of host damage pathog enicity 2 toxigenicity ability to produce toxins 3 toxemia symptoms caused by toxins in blood exotoxins secreted proteins usually enzymes 1 exotoxin not bacterium produces disease symptoms a usually produced by gram positives b genes often plasmid encoded c tend to be very toxic 1 mg botulinum toxin enough to kill 1 million guinea pigs 2 antitoxins antibodies produced against exotoxins 3 cytot oxins kill host cells or affect mctions a diphtherotoxin inhibits protein synthesis b erythrogenic toxins damage capillaries neurotoxins interfere with nerve impulses a botulinum toxin pr events nerve transmission b tetanus toxin prevents inhibitory nerve transmission enterotoxins affect cells lining the GI tract inducing uid and electrolyte loss quotom host cells a Vibrio choleragen b staphylococcal ent ero toxin endotoxins part of outer wall of cell wall of gram negative bacteria lipid portion of lipopolysaccharide layer lipid A endot oxins lipop olysacchar ides exo toxins 2 endotoxin released when cells are lysed a cell death b antibiotics c antibodies all produce fever pyrogenic response weakness aches sometimes shock 4 v 5 v A H v proteins 3 v 4 do not promote formation of effective antito xins a antitoxin speci c antibody produced in response to an exotoxin or its toxoid b antibodies are produced but they do not counter the effect of the toxin and can often enhance its effect 7 hypersensitivity allergy exaggerated or heightened immune reaction that is injurious a contact with heterophile antigens on bacteria can cause a host to produce antibodies against any A or B antigens they are lacking b these antibodies can react with these antigens ifthe wrong blood type is trans ised without regard to compatibility F Host defense mechanisms resistance ability to ward off diseases through body de nses a susceptibility lack of resistance b nonspeci c resistance all defenses that protect host om any kind of pathogen c specific resistance antibodies against speci c microorganisms 2 skin and mucous membranes protect through a combination of mechanical and chemical factors a mechanical factors include physical barrier to microbial invasion 1 intact skin dif cult to penetrate 2 keratin skin protein is waterproof 3 some pathogens in large nurrbers can penetrate mucous membranes b bacteria can be washed from surfaces lacrimal apparatus in eyes 2 saliva washes MO quotom teeth and gums 3 urine move MO out of urinary tract 4 vaginal secretions move MO out of vagina perspiration washes MO off skin mucus traps many MO that enter respiratory or G1 tracts d sebum contains unsaturated fatty acids which can inhibit pathogens 1 sebum oily substance produced by sebaceous glands that coats some areas of skin and keeps hair quotom getting brittle some skin bacteria metabolize sebum and cause the in ammatory response associated with acne e lysozyme in tears saliva nasal secretions and perspiration lyse bacteria f high acidity pH 1230 of gastric juice prevents microbial growth in stomach and kills many ingested organisms g normal ora prevent the growth of many pathogens 3 phagocytosis is the ingestion of MO or particulate matter by phagocytes a phagocytes white blood cells or derivatives leukocytes 1 infection stimulates WBC synthesis leukocytosis 2 two types of phagocytotic WBC a neutrophils a type of granulocyte commonly called polymorphonuclear leukocytes PMNs A H v A U v 0 2 v b monocytes which lack granules and mature into macrophages once they leave blood and enter tissues 3 neutrophils are highly ph ago cytic and mo tile a able to leave the blood enter tissues and destroy microbes b active in initial stages of infection 4 monocytes more active in later stages of infection b phagocytosis involves four major steps 1 phagocytes attracted to M0 by chemotaxis 2 phagocyte adheres to the MO 3 phagocyte ingests MO 4 phagocyte digests MO 4 In ammation is a response to bodily damage characterized by redness pain heat swelling and sometimesloss of function a vaso dilation and increased permeability of blood vessels 1 vasodilation increase in diameter ofblood vessels a increases blood ow to damaged area b responsible for redness and heat 2 increased permeability allows defensive substances normally retained in blood to pass into injured area a responsible for swelling 3 vasodilation and increased permeability induced by histamines kinens prostaglandins and leukotrienes b phagocytes squeeze through blood vessels into infected tissue c pus is the accumulation of damaged tissue and dead microbes granulocytes and macrophages d repair final stage of in ammation 5 fever abnormally high body temperature produced in response to bacterial or viral infection a increased body temperature increased production of immune system components b may inhibit grth of some bacteria c may increase repair rate 6 the body produces certain antimicrobial substances in addition to chemical already mentioned a interferons probably best known b interferons are antiviral proteins 1 3 types of human interferon 2 induce uninfected cells to produce antiviral proteins that prevent viral replication a good only on shortterm basis b does not prevent viral multiplication in cells already infected 3 hostcell speci c but not virus speci c G The immune system 1 an inducible system that acts as the last line of defense a activation indicates that general resistance mechanisms have failed b must have an extensive repertoire but focus on speci c foreign substance c must be shut down upon removal of foreign material types of immunity a innate genetic 1 genetically determined 2 species immunity b acquired immunity 1 natural by having a disease 2 arti cial vaccination c active vs passive 1 active own system produces antibodies a naturally acquired active immunity from disease b artificially acquire d active immunity quotom vaccine 2 passive a naturally acquired passive immunity antibodies from mother passed to offspring b artificially acquired passive immunity antibodies obtained quotom other ho sts antigen immunogen substance the body identifies as foreign and mounts a defense against a most are large proteins MW gt 10000 1 polysaccharides or protein complexes glycoprot eins nucleoproteins work well 2 lipid work poorly b epito pe antigenic determinant antibody antiantigen protein produced by immune system against antigens lyrrphocytes cells that carry out speci c immune responses a develop quotom stem cells like other wbc rbc and platelets b B cells or B lymphocytes mature in bur sal cells of birds or equivalent in humans 1 most believe they develop in bone marrow or gutasso ciated lymphoid tissues 2 about onefourth of lymphocytes circulating inblood c T cells or T lymphocytes undergo differentiation in the thymus 1 as adults thymus less active di erentiation occurs in blood marrow or tissues underthe influence of hormones frm the thymus 2 four dif rent types a cytotoxic killer T cells b delayedhyper sensitivity T cells c helper T cells d suppressor T cells humoral immunity is carried out by antibodies circulating in the blood a B cells release antibodies b most effective against bacterial toxins bacteria and viruses before they enter cells c lgG makes up about 80 of plasma antibodies 1 appears in all body uids 2 major antibacterial and antiviral antibody d lgM is the first immunoglobulin produced during immune response 1 very large 2 usually found only in vascular system e lgA is found mainly in bodily secretions 1 saliva sweat tears mucus bile and colostrum 2 defends against surface pathogens especially those that enter the respiratory and GI tracts f IgD is the predominant antibody on the surface of B cells and acts mainly as an antigen receptor g IgE is involved in hypersensitivity reactions 1 develops within minutes of exposure to antigen 2 stimulates the release of mast cell granules which contain histamine and heparin h in ammatory response is part of humoral immunity 7 cell mediated immunity is carried about by T cells a works against antigens in cell membranes or inside cells b defends primarily against virusinfected cells but can also work with eukaryotic parasites cancers and foreign tissues transplants 8 recognition of self a major histocompatibility complex MHC 1 cell surface components 2 secondary interactions b clonal selection theory 1 timing of expo sure between lymphocyte s and antigens determines if it is recognized as self or not 2 early expo sure embryonic development leads to destruction of speci c lyrrphocytes speci city different reactions of immune system to each foreign substance 10 heterogeneity ability for immune system to respond to all the different antigens encountered 11 memory recognition of antigens previously encountered a memory cells produced b memory cells have different lifetimes 12 immunoglobulins antibodies a Yshap ed molecules made up of two light chains and two heavy chains b constant and variable regions responsible for different combinations H Immune Disorders 1 hypersensitivity allergies a immune system overreacts b can harm the host c usually treated with antihistimines d several different manifestations 1 allergic rhinitis hay fever 2 urticaria hives 3 asthma 2 autoimmunity a immune system attacks host b several manifestations 1 rheumatoid arthritis 2 lupus erythematosus IV Control of Growth inanimate objects A Terminology antiseptic cide lytic 7 amewwr sterilization destruction of living cells viable spores viruses viroids disinfection killing inhibition or removal of organisms sanitizat ion reduction of micro organisms to safe health levels chemical agents applied to tissues to kill or inhibit pathogens kills organisms lyse s or ganisms static inhibits grth of organisms B E ectiveness of antimicrobials 1 population death is generally exponential or logarithmic 2 ef ciency of antimicrobials influenced by at least 6 factors a population size larger population requires more time to die b population composition different degre es of re sistance between different organisms or structures 1 spores more resistant than vegetative cells 2 Mycobacterium tuberculosis acidfa st more resistant than most bacteria 3 young cells more readily destroyed than older cells c concentration of antimicrobial 1 usually greater concentration greater effectiveness 2 70 ethanol more eff ctive than 95 ethanol d exposure duration 1 longer exposure greater death 2 sterilization reduction of survival probability to 10 e temperature increase usually increases eff ctiveness of chemical f local environment 1 heat kills better at acid pH 2 efficiency higher with lower organic matter C Heat 1 moist heat a boiling kills viruses bacteria ingi b 10 minutes boiling kills vegetative cells not endospores c pressurized steam autoclave 1 autoclave fancy pressure cooker 2 combines wet heat with pressure allows temperatures above 100 C 3 temperatures above 100 C required to destroy endospores 4 chamber lled with saturated steam for 121 C 15 psi 5 materials exposed for 15 minutes thermal death time TDT shortest period of time to kill all organisms at a speci c temperature under de ned conditions decimal reduction time D or D value time to kill 90 1 important to food industry 2 usually assumed population of 1012 cells reduced to 100 3 ifD for C botulinum spores is 0204 minutes at 121 C 12D 25 minutes 4 z value increase in temperature required to reduce D to 110 its value a for C botulinum z 10 C b at 111 C D 204 minutes 12D 245 minutes pasteurization 1 reduces microorganism numbers but retains avor of foo ds especially dairy beer and other beverages 2 brief heating followed by rapid cooling 3 63 66 C for 30 minutes batch or older method 4 ash pasteurization 72 C for 15 seconds 5 UHT 134 C for l 2 seconds g tyndallization discontinuous boiling or fractional steam sterilization 1 heat material to 90 100 C for 30 minutes on 3 consecutive days incubated at 37 C 2 1st heating destroys cells but leaves endospores 3 2nd and 3rd heating destroys germinating endospores 2 Dry heat sterilization a 160 170 C for 23 hours b cell constituents oxidize c less e fective than moist heat 3 Filtration a physical removal of microorganisms 1 excellent for heat sensitive materials 2 can be used with gases b depth lters thick layers of brous or granular material 1 twisting channels of small diameter 2 microbes removed by physical entrapment and adsorption to lter material c membrane lters thin 01 mm membranes 1 made of cellulose acetate cellulose nitrate polycarbonate po lyvinylidene chloride or other synthetic materials 2 vegetative cells removed with 02 m pore size 4 Radiation a alters DNA causing lethal mutations b UV ultraviolet light 260 nm 1 doesn39t penetrate glass dirt lms water many plastics 2 often used to sterilize cabinets or entire rooms c ionizing eg gamma 1 penetrates objects 2 also called cold sterilimtion CL 0 1395 3 widely used with food D Chemical methods 1 chemicals react with and destroy function of cell components 2 phenolics a early use by Lister b Lysol contains a mixture of phenolics c denature proteins and disrupt cell membranes d excellent for surfaces but can muse skin irritation alcohols a bactericidal and mgicidal but not sporicidal b denature proteins and dissolve membrane lipids halogens a iodine most common followed by chlorine b tincture of iodine 2 iodine in waterethanol solution of potassium iodide 1 effective antiseptic 2 stains and may damage skin 3 iodophor complex of iodine organic carrier a water soluble stable nonstaining b slow release to prevent skinburns and irritation c chlorine disinfectant of choice for municipal water supp lies and swimming pools 1 added in many forms forms hypochlorous acid 2 oxidizes several materials destroying cells but not endospores 3 Halzone tablets used for personal drinking water 4 excellent household disinfectant a 1100 dilution of household bleach 13 02 gal 07 nonionic detergent 1 o zg al b cleans and kills bacteria heavy metals a Hg Ag As Zn Cu used to be common germicides 1 most heavy metals are bacteriostatic not bactericidal 2 currently using less toxic more effective germicides 3 1 silver nitrate added to eyes of infants to prevent ophthalmic gonorrhea being replaced by erythromycin which is also e ective against Chlamydia and Neisseria 4 silver sulfadiazine used on burns 5 copper sulfate used as algicide in lakes and swimming pools b combine with proteins sulfhydryl groups inactivating them quaternary ammonium compounds a detergents emulsi ers 1 amphipathic molecules 2 e ective cleansing agents cationic detergents more antimicrobial than anionic detergents 1 quaternary ammonium corrpounds most popular 2 positively charged quaternary nitrogen with long hydrophobic aliphatic chain organic molecules nonso aps that serve as wetting agents and P C disrupt membranes and may denature proteins d kill most cells but not endospores orM tuberculosis 6 often used as disinfectants for food utensils small instruments and skin antiseptics 7 aldehydes a formaldehyde and gluteraldyde most common b combine with and deactivate proteins c 2 glutaraldehyde commonly used to disinfect hospital equipment 8 gases a ethylene oxide is both microbicidal and sporicidal 1 combines with cell proteins 2 penetrates packing materials even plastic wraps b explosive usually done in special sterilizer V Antimicrobial chemotherapy living systems A History 1 chemotherapeutic agents chemical agents used to treat disease a destroy or inhibit growth of patho gens b concentrations low enough not to damage host c include antibiotics microbial pro ducts or their derivatives that can kill or inhibit gro wth of microorganisms 2 Paul Erlich began the modern age ofchemotherapy a 0 magic bullet pathogens 1 particularly interested in syphilis and African sleeping sickness 2 normal syphilis treatment was ingestion of toxic mercury compounds often patients died 3 trypanosomiasis treated similarly with arsenic compounds 4 deliberately tned preparing organic material containing arsenic which would be less lethal to humans arsphenamine Erlich 60 6 was effective against syphilis trade name Salversan lt noted that dyes were strongly taken up by bacteria so studied those for speci c toxicity 1 trypan red was effective against the trypanosome that causes A quotican sleeping sickness 2 acri avine yellow dye still in use a good for super cial wounds and skin infections b too toxic for internal use chemical toxic dye that would speci cally bind to and destroy established the concept of selective toxicity led to testing of hundreds of compounds 1 Gerhard Domagk found that Prontosil Red killed pathogenic staphylococci and streptococci but didn39t harm the animal 2 Jacques and Therese Trefouel discovered that Prontosil Red was convertedto sulfanilamide the true active factor 3 led to development of sulfa drugs sulphonamides a speci cally designed go stay in gut or be absorbed in bloodstream b often more active against microbes and less toxic to humans than sulfanilamide c tremendously effective against pneumonia puerperal fever systemic infection due to Streptococcus pyogenes d general structure similar to PABA some microbes require PABA for growth f sulfa drugs are competitive inhibitor prevent growth and allow body39s defense mechanisms to deal with microbes g during 4039s and 5039s many vitamins discovered and inhibitory analogs made 1 worked in test tubes 2 too toxic in humans eliminated too well by kidneys vitamin concentration in tissues too high or infecting bacteria did not require vitamin 3 not one drug was of practical therapeutic importance 4 penicillin rst antibiotic to be used therapeutically a originally observed by 21year old French medical student Ernest Duchesne rediscovered by Alexander Fleming b Fleming observed a contaminant mold which seemed to be dissolving Staphylococcus colonies 1 found that broth from aPenicillium culture could destroy a number of patho gens 2 unable to purify the active compound very well 3 published some papers and abandoned the area c Howard Florey and Ernst Chain 1939 obtained Penicillium notatum from Fleming 1 puri ed penicillin 2 destroyed staph and strep infections in mice 3 Fleming Florey and Chain shared 1945 Nobel 5 Selman Waksman1944 discovered streptomycin an antibiotic produced by the actinomycete Streptomyces griseus Nobel 1952 a b led to increased search for other antibiotic producers by 1953 microbes producing chloramphenicol neomycin terramycin and tetracycline were isolated B Characteristics of antimicrobials 1 selective toxicity kill or inhibit pathogen without damaging host a b c d therapeutic dose infection toxic dose drug level at which the agent becomes too toxic for host therapeutic index ratio of toxic dose to therapeutic dose larger number better drugs speci c for microbial Jnct ion that doesn39t occur in ho st eg cell wall synthesis have highest therapeutic index drug level required for clinical treatment of a particular 2 range of ef ctiveness varies a b c d narrowspectrum effective against a limited number broadspectrum effective against many types of pathogens can be classi ed based on targeted group 1 antibacterial 2 anti lngal 3 antiprotozoan 4 antiviral some agents are effective against more than one group e g sulfa drugs work against bacteria and some protozoa 3 chemotherapeutic agents can be natural synthetic or semisynthetic a synthetics are 1 sulfa drugs 2 trimethoprim 3 chloramphenicol 4 isoniazid 5 dapson 6 many antiviral and antiprotozo an drugs semisynthetic are natural antibiotics that have been chemically modified to make them less susceptible to inactivation 1 ampicillin 2 wrbenicillin 3 methicillin 4 chemotherapeutic agents can be cidal or static a b c can be concentration dependent effect varies with species static effect relies on host39s defense mechanism for elimination of infection C Determining activity levels 1 dilution susceptibility tests a b a series of broth tubes containing a range of antibiotic concentrations inoculated with test organism minimal inhibitory concentration MIC growth no growth after 1620 hr lowest concentration that prevents c minimal lethal concentration MLC lowest concentration that kills the organism no growth in subculture d cidal drugs usually kills at 24x MIC static drugs kill at much higher concentrations if at all 2 disk diffusion tests a antibiotic irrpregnated disks are placed on agar previously inoculated with the test bacterium 1 antibiotic dif lses forming a gradient 2 resistant organisms grow up to the disk 3 susceptible organisms grow some distance from the disk displaying a clear zone around the disk a wider the clear zone more susceptible b zone width is a function of initial concentration solubility dif lSiOl l rate susceptibility of organism c zone width cannot be used to compare 2 antibiotics b KirbyBauer most used disk dif lsion test 1 Mue ller Hinton agar inoculated with lawn of bact eria 2 disks placed on surface 3 incubation at 35 C for 1620 hr 4 diameters of zones measured and compared to tabulated values to determine degree of microbial resistance a plot MIC vs zone diameters for different strains b determine from plot if treatment dosage would result in MIC D General mechanisms of activity H pathogen damage can occur through several mechanisms a most selective antibiotics interfere with cell wall synthesis b high therapeutic index since cell walls not sound in eucaryotes Cell wall synthesis inhibition a penicillin ampicillin carbenicillin methicillin cephalospor ins b inhibit enzymes for peptidoglycan crosslinking activate cell wall lytic enzymes c bacitracin inhibits CW synthesis by interfering with lipid carrier that transports precursor s acro ss the plasma membrane protein synthesis inhibition a streptomycin gentamicin bind to 30 ribosome subunit and causes misreading of mRNA b chloramphenicol binds to SOS ribosomal subunit inhibits peptidyl transferase blocking peptide fond formation c tetracyclines bind to 30 interfere with aminoacyl tRNA binding d erythromycin binds to SOS inhibits peptide chain elongation e high therapeutic index because drugs differentiate between procaryotic and eucaryotic ribosomes 4 nucleic acid synthesis inhibition a rifampicin b inhibits DNAdependent RNA polymerase blocking RNA synthesis c often toxic to eucaryotic systems also 5 Cell membrane disruption a polymyxin B b binds to cell membrane disrupts structure and permeability metabolic antagonism antimetabolites a sulfa drugs compete with PABA inhibits folic acid synthesis b trimeth oprim inhibits dihydro folate reduct ase blocking tetr ahydr ofo late synthesis c dap sone interferes with folic acid synthesis d isoniazid may disrupt pyridoxal or NAD metabolism and functioning inhibits synthesis of mycolic acid quotcord factorquot Several factors determine effectiveness of antimicrobial drugs a drug must reach site of infection so delivery system important 1 penicillin G unstable in stomach acid 2 gentamicin aminoglycosides not well absorbed through gut and must be inject ed int ramu scularly 3 parenteral routes nonoral administration b concentration must exceed MIC 1 dependent on amount administered 2 speed of uptake 3 rate of elimination from body 4 best if drug is absorbed slowly over a long period and excreted slowly c infecting organism 1 dormant bugs less susceptible 2 pathogen must have proper target site d many agents less effective due to resistance mechanisms spread quickly via plasmids E Classes of antibiotics 1 4 5 sulfa drugs a structural analog similar to metabolic intermediate b similar to PABA necessary for synthesis of folic acid quinolones a synthetic drug broad spectrum bactericidal b inhibits DNA replication and repair transcription c nalidixic acid uor oquino lones c ipro oxa cin norfoxacin o oxacin penicillins a lactam ring is common feature side chains vary b penicillinase destroys ring c block peptidoglycan cross linking leading to lysis d many people are allergic cephalo spor ins a originally isolated quotom Cephalosporium mgus b lactam ring like penicillins c use il for people allergic to penicillin d broad spectrum tetracyclines a naturally produced by Streptomyces or semi synthetic b bind to 3 OS ribos omal subunit inhibiting protein synthesis c bact erio static d broad spectrum 6 aminoglycoside antibiotics a Streptomyces make streptomycin kanamycin tobramycin b Micromonospora purpurea synthesizes gentamicin c bind to small ribo somal subunit inhibiting protein synthesis d bactericidal most effective against gram negatives e quite toxic to humans f Widespread resistance 7 erythromycin a macrolide synthesized by Streptomyces erythraeus b broad spectrum bacteriostatic most ef ctive against G c bind to 23S rRNA of SOS ribosomal subunit inhibiting protein elongation d macrolides have 12 to 22carbon lactone rings chloramphenicol a synthetic but originally from Streptomyces venezuelae b acts like erythromycin c broad spectrum bacterio static d quite toxic to humans F Mechanisms of drug resistance drug mnnot enter cell a G unaffected by penicillin G because it can39t penetrate the out er membrane b changes in binding proteins render cells resistant 2 chemical modification a penicillinase hydrolyzes the lactam ring b groups can be added which inactivate drugs 3 modi cation of target a changes in 23S rRNA protects against chloramphenicol or erythromycin b change binding site for sulfanilamide 4 genes for drug resistance can be chromosomal or on plasmids a spontaneous mutations in chromosome are rare b chromosomal changes usually result in changes in drug receptors preventing 9 binding c R plasmids resistance plasmids often code for enzymes that de str oy or modify drugs 1 i it J in i t0 penic lins cephalosporans erythromycin tetracyclines sulfonamides chloramphenicol and others 2 plasmids transferred rapidly through populations 3 single plasmid can carry resistance to many drugs 5 Overuse of antibiotics has led to many resistant strains a increase drug concentrations to destroy susceptible and spontaneous mutants b use two drugs together c limit use especially broadspectrum antibiotics G Anti mgal drugs 1 eukaryotic s0 drugs Often toxic to humans 2 most fungi have ef cient detoxi cation mechanisms 3 Often target membrane st ero ls or cell walls H Antiviral drugs 1 most drugs disrupt critiml stages in Virus life cycle or synthesis OfViralspeci c nucleic acids 2 di icult to use drug therapy since Viruses use host39s cell machinery Terminology for Control of Microbial Growth W antimicrobial agent cidal agents static agaits lytic agents minimim inhibitory concentration MIC agar diffusion method disinfectant sepsis antiseptic germicide Physical M ethods thermal death time TDT tyndallization pasteurization ultra high terrperature UHT processing incineration irradiation ltration chemical that kills or inhibits growth of micr oorganisms kill organisms eg bactericidal fungicidal algicidal inhibit growth e g bacteriostatic fungistatic algistatic induce cell lysis e g bacteriolytic smallest amount of an agent needed to inhibit growth of a test organism antimicrobial action determined by zones of inhibition concentration at zone edge equivalait to MIC chemical used to kill microorganism on inanimate objects presence of microorganisms in tissues or blood chemical agent that kills or inhibits microorganisms on living tissues chemical agent that kilk pathogenic microbes on inanimate objects shortest time required to kill all microbes at a speci edtemperature discontinuous boiling heated at 63 66 C for 30 minutes batch method or 7160 C for 15 seconds ash method to reduce microbe numbers and retain avor heat at 134 C for 1 2 seconds can sterilize some foods ie milk allowing unrefrigerated shelf lives of several months most rigorous heat treatment bombardment with radiation causes mutations microbes removed bypassage through small pore e g 22 m membranes From quotMicrobes and Manquot Postgate John 1992 3rd ed Cambridge Press quotquot in fact thequot in fact the body has at least four lines of defence The first isquot in f calledcalled lysozymecalled lysozyme which is found in saliva tears and nose mucus an propertyproperty of dissolving many bacteria Tproperty of dissolving many bacteria collectivelycollectively called interferon proteins produced by viruscollectively called int4 interfereinterfere with the further growth of viruses interfere with the further growth of vir basedbased on the fact thatbased on the fact that the blood contains certain white corpusc whichwhich are rather like domesticated protozoawhich are rather like domesticated SomeSome of them known as phagocytes actuallySome of them known as phagocytes act39 microbesmicrobes that get in If a slight would occursmicrobes that get in If a slight woul phagocytesphagocytes to congregatephagocytes to congregate near the sitephagocytes to c infection quot How does the bodyHow does the body cope with aHow does the body cope with a well est cells quotMassivequotMassive microbial growthquotMassive microbial growth only occurs if39Massive micrlt brokenbroken down and then one is very ill and if the bacteria produce particularly nastynasty toxins one may die If one recovers the rnasty toxins one may die If defencedefence mechanismdefence mechanism has been successful thedefence mechani calledcalled antibodies which dissolved incalled antibodies which dissolved in the blood s microbesmicrobes and cause them to coagulate in lumps In thismicrobes and cause them harmharm and are more easilyhann and are more easily ingested by the phagocytes The isis nowis now immune to the particular microbeis now immune to the particular microb sometimessometimes only for a few months sometimesometimes only for a few montlquot lifetime quot Facto rs Causes of Death Lifestyle Environmen Genetics Health Care t Services Heart Disease 54 9 25 12 Cancer 37 24 29 10 Stroke 50 22 21 7 COPD 80 5 6 9 Unintentional Injuries 73 18 1 8 In uenzapneumonia 23 20 39 18 Diabetes 34 0 60 6 AIDS 85 5 5 5 Suicide 60 3 5 2 3 Liver Disease 70 9 18 3 All Ten Causes 56 15 21 8 Hamann Br 2001 Disease Identi cation Prevention amp Control 2 ed McGraw Hill New York Pesticides A Chemical poisons used to kill pests natural pesticides are produced by insects plants or can be heavy metals 2 synthetics are manufactured a about 600 active ingredients b about 40000 synthetic pesticides in use today B Synthetic pesticides widely used on food crops such as wheat corn and soybeans a approximately 500000 tons applied to crops each year b about 13 of food crops still lost to pests 2 home gardens and lawns 3 originally hailed as miracle workers that would end world hunger 4 public became more aware of health risks a no discrimination between pests and good organisms b changes in ecosystems c risk to agricultural workers public at large d could be responsible for amphibian disappearance C Organochlorine pesticides l DDT hetachlor chlordane lindane brand name Kwell used to kill lice a FDA warns that overuse of lindane could have toxic effects b other three are carcinogens c still manufactured for export 2 contaminated foods can be shipped to the US a circle of poison 1 export banned pesticides 2 banned pesticides used on food crops 3 food shipped back to country selling the pesticide b heptachlor and chlordane have been found in imported milk and beef products D Organophosphate pesticides 1 used in pesticides and chemical weapons 2 parathion a common organophosphate a strictly regulated in U S b used on many crops and a leading cause of farm worker poisoning c neurotoxin that poisons on contact 1 dizziness to convulsions 2 death due to respiratory failure 3 suspected carcinogen 4 spills have caused massive fish kills 3 many pests are now resistant to organophosphate pesticides E Natural pesticides 1 generally not as effective as synthetics but safer 2 natural products or based on natural products a botanicals b biological pesticides 3 synthetic pyrethoid a similar to natural compound in chrysanthemums b low toxicity quickacting on insects low persistence in the environment c not absorbed into skin as much as organochlorines and organophosphates but toxic when swallowed d Resmethrin kills flying insects indoors e Pemethrin is used in ea sprays and in agriculture 4 Dipel trade name for Bacillus Ihuringiensis a attacks caterpillars and other insects in larval stage genetic recombination for Bt toxin in plants 5 insecticidal soaps are used on aphids F Assessing risk 1 identify potential health effects 2 determine doseresponse LDSO 3 assess exposure ris a inhalation absorption through skin ingestion b ood c homepersonal use d pesticides in drinking water e ex osure at work 4 risk characterization risk toxicity x exposure 5 low dose long term effects have been ignored Problems with risk assessment 1 pesticide regulatory studies only assess single exposures to single active ingredients 2 pesticide testing is not done with children or other susceptible groups in min 3 pesticide testing only studies certain kinds of human health risks a acute poisoning b cancer c neurotoxic effects 4 pesticide testing is largely the responsibility of the manufacturers 5 federal law prohibits the advertising of pesticides as safe even if used as directed 6 inert ingredients may account for 99 are not divulged to consumers applicators state agencies or physicians everything but the active ingredient is allowed to be described as inert and is protected as a trade secret b canceled pesticides DDT chloroform c known carcinogens benzene toluene d industrial solvents m ethylene chloride trichloroethane e Toxic Substances Control Act substances dimethylpthalate methyl bromide 7 following directions and professional practices does not eliminate an exposure risk a long persistence times for synthetic pesticides b accumulation in body tissues c biological breakdown takes a long time d degradation can produce even more toxic metabolites Lowering risk 1 wash fresh produce well a peel and skin fruits if possible b scrub vegetables thoroughly 2 store household pesticides in safe ways a exposure at home from poor storage under sink b during colder months houses closed tight c ingestion especially by children 3 chronic exposure linked to increased risk of cancer especially in children Accumulation 1 government report CDC due in early 2001 a survey of levels of lead pesticides other undesirable substances in blood b exposure through environment and diet 2 comparison with existing data to determine possibility of links a cancer b hormonal problems 1 child development 2 infertility 3 25 compounds to be investigated heavy metals including lead tobacco products organophosphate pesticides phthalates used to soften plastics dioxins 020057 J f PCBs l manufacture of electrical components industrial waste 2 slow to degrade in environment 3 accumulates in fatty tissue 4 manufacture banned in 1977 Chronic problem s l data from recent laboratory tests wildlife research and accidental human exposure studies indicate that synthetic chemicals including pesticides can cause serious damage at extremely low levels bulk of pesticide research focuses on poisoning or carcinogenicity many chemicals like hormones can have profound effects at low concentrations accumulation of synthetic pesticides in body tissues is virtually permanent a men have an everincreasing load of chemicals b women can only lose it through breast milk or across the placenta to a developing fetus pesticides can have reproductive or endocrinedisrupting effects 39 39 hormones b bind to hormone receptors to Have Possible Effects of Endocrine Disrupters infertility I endometriosis I breast cancer I altered fetalchild development testicular cancer I prostate enlargement I low sperm count I learning disorders endocrine disrupters cause birth defects infertility and learningdisabilities a in western world have 50 lower sperm counts than in 1938 b reproductive system cancers 1 breast 2 testicular endocrine disrupters are transferred to the fetus a affects fetal development b affects children some evidence suggests a detrimental effect on the immune system a immunotoxicity not teste une systems ofmammals are very similar population studies support lab studies showing immunotoxic effects in irect evidence for cancer types found in groups occupationally exposed to pesticides b direct studies in form er Soviet Union looking at populations in regions of heavy pesticide use c direct studies of Canadian lnuits who ingest a high level of pesticides in their iet l Inuit children 30x more likely to contract meningitis 2 suffer chronic otitis ear infections at epidemic rates Categories of Acute Toxicity Cate 0 Signal Word Oral Dermal Inhalation Approximate Oral dose that can g ry Required 0n Label Ld50 LD50 LC50 mgl Kill an Average Person Mgkg mgkg DANG I Highly toxic Poisonl Skull From 0 to From 0 to From 0 to 02 A few drops to 1 teaspoon full or a 50 200 few drops on the skin Crossbones II Moderately From 50 From 200 to I Toxic WARNING to 500 2000 From 02 to 2 Over 1 teaspoonful to 1 ounce III Slightly H From 500 From 2000 Toxic CAUTION to 5000 to 20 000 From 20 to 20 Over 1 ounce to 1 pint or 1 pound III Slightly More than More than Greater than Toxic CAUTION 5000 20 000 20 Over 1 pint or 1 pound Toxicity Categories for Pesticides Hazard Indicators I H III IV Greater than Oral LDSO Up to and including From 50 through 500 mgkg From 500 through 5000 5 000 50 mgkg mgkg mgkg From 20 through 20 mgl From 20 through 200 mgl Inhalation Lcso a Dust Up to and including Greater than or mist 20 mgl 200 mgl Inhalation Up to and including From 2000 through Greater than LC50 b Gas 200 pm From 200 through 2000 pm 20 000 pm 200 pm or vapor Greater than Up to and including From 2000 through Dermal LD50 200 rugkg From 200 through 2000 mgkg 20 000 rugkg 20000 mgkg Irreversible corneal Corneal opacity reversible Within 7 cqmeal Opa ilty No Eye effects irritation revers1ble Within opacity at 7 days days or irritation pers1sting for 7 days 7 days irritation Severe irritation or Skin irritation dam age at 72 Moderate irritation at 72 hours hours Mild or slight irritation at No irritation 72 at 72 hours Pesticides A Chemical poisons used to kill pests natural pesticides are produced by insects plants or can be heavy metals 2 synthetics are manufactured a about 600 active ingredients b about 40000 synthetic pesticides in use today B Synthetic pesticides 1 widely used on food crops such as wheat corn and soybeans a approximately 500000 tons applied to crops each year b about 13 of food crops still lost to pests 2 home gardens and lawns 3 originally hailed as miracle workers that would end world hunger 4 public became more aware of health risks a no discrimination between pests and good organisms b changes in ecosystems c risk to agricultural workers public at large d could be responsible for amphibian disappearance C Organochlorine pesticides 1 DDT hetachlor chlordane lindane brand name Kwell used to kill lice a FDA warns that overuse oflindane could have toxic effects b other three are carcinogens c still manufactured for export 2 contaminated foods can be shipped to the Us a circle ofpoison 1 export banned pesticides 2 banned pesticides used on food crops 3 food shipped back to country selling the pesticide heptachlor and chlordane have be en found in imported milk and beefproducts D Organophosphate pesticides 1 used in pesticides and chemical weapons 2 parathion a common organophosphate a strictly regulated in Us b used on many crops and a leading cause of farm worker poisoning c neurotoxin that poisons on contact 1 dizziness to convulsions 2 death due to respiratory failure 3 suspected carcinogen 4 spills have caused massive fish kills 3 many pests are now resistant to organophosphate pesticides E Natural pesticides generally not as effective as synthetics but safer 2 natural products or based on natural products a botanicals b biological pesticides 3 synthetic pyrethoid a similar to natural compound in chrysanthemums b low toxicity quick acting on insects low persistence in the environment c not absorbed into skin as much as organochlorines and organophosphates but toxic when swallowed d Resmethrin kills flying insects indoors e Pemethrin is used in ea sprays and in agriculture 4 Dipel trade name for Bacillus thuringiensis a attacks caterpillars and other insects in larval stage b genetic recombination for Bt toxin in plants 5 insecticidal soaps are used on aphids Assessing risk identify potential health effects 2 determine dose response LDSO 3 assess exposure risk a inhalation absorption through skin ingestion b food c homepersonal use d pesticides in drinking water e exposure at work 4 risk characterization risk toxicity x exposure 5 low dose long term effects have been ignored Problems with risk assessment pesticide regulatory studies only assess single exposures to single active ingredients 2 pesticide testing is not done with children or other susceptible groups in mind 3 pesticide testing only studies certain kinds ofhuman health risks a acute poisoning b cancer c neurotoxic effects 4 pesticide testing is largely the responsibility ofthe manufacturers 5 federal law prohibits the advertising of pesticides as safe even if used as directed 6 inert ingredients may account for 99 are not divulged to consumers applicators state agencies or physicians a everything but the active ingredient is allowed to be described as inert and is protected as a trade secret b canceled pesticides DDT chloroform c known carcinogens benzene toluene d industrial solvents methylene chloride trichloroethane e Toxic Substances Control Act substances dimethylpthalate methyl bromide 7 following directions and professional practices does not eliminate an exposure risk a long persistence times for synthetic pesticides b accumulation in body tissues c biological breakdown takes a long time d degradation can produce even more toxic metabolites Lowering risk wash fresh produce well a peel and skin fruits ifpossible b scrub vegetables thoroughly 2 store household pesticides in safe ways a exposure at home from poor storage under sink b during colder months houses closed tight c ingestion especially by children 3 chronic exposure linked to increased risk of cancer especially in children Accumulation government report CDC due in early 2001 a survey oflevels of lead pesticides other undesirable substances in blood b exposure through environment and diet 2 comparison with existing data to determine possibility of links a cancer b hormonal problems 1 child development 2 infertility 3 25 compounds to be investigated a heavy metals including lead b tobacco products c organophosphate pesticides d phthalates used to soften plastics e dioxins f PCBs 1 manufacture of electrical components industrial waste 2 slow to degrade in environment 3 accumulates in fatty tissue 4 manufacture banned in 1977 I Chronic problems 1 data from recent laboratory tests wildlife research and accidental human exposure studies indicate that synthetic chemicals including pesticides can cause serious damage at extremely low levels a bulk of pesticide research focuses on poisoning or carcinogenicity b many chemicals like hormones can have profound effects at low concentrations 2 accumulation of synthetic pesticides in body tissues is virtually permanent a men have an ever increasing load of chemicals b women can only lose it through breast milk or across the placenta to a developing fetus 3 pesticides can have reproductive or endocrine disrupting effects a mimic hormones b bind to hormone receptors Pesticides to Have and Endocrine Effects lindane malthion chlordane dicofol dieldrin mirex DDT hetachlor endosulfan Possible Effects ofEndocrine Disrupters infertility endometriosis I breast cancer altered fetalchild development testicular cancer I prostate enlargement I low sperm count I learning disorders 4 endocrine disrupters cause birth defects infertility and learningdisabilities a men in western world have 50 lower sperm counts than in 1938 b reproductive system cancers 1 breast 2 testicular 5 endocrine disrupters are transferred to the fetus a affects fetal development b affects children 6 some evidence suggests a detrimental effect on the immune system a immunotoxicity not tested b immune systems ofmammals are very similar 7 population studies support lab studies showing immunotoxic effects a indirect evidence for cancer types found in groups occupationally exposed to pesticides b direct studies in former Soviet Union looking at populations in regions ofheavy pesticide use c direct studies of Canadian Inuits who ingest a high level ofpesticides in their diet 1 Inuit children 3 Ox more likely to contract meningitis 2 suffer chronic otitis ear infections at epidemic rates Categories of Acute Toxicity Signal Word oral Dermal Inhalation Approximate Oral dose that can Category Ld50 D50 Required on Label LC50 rngl Kill an Average Person Mgkg rugkg DANGER A f d t 1 t f 11 IHighly toxic Poison Skull From 0 to From 0 to From 0 to 02 W mpg 0 6361300 or a few drops on the skin Crossbones II Moderately From 50 From 200 I Toxic WARNING to 500 to 2000 From 02 to 2 Over 1 teaspoonful to 1 ounce III Slightly From 500 From 2000 From 20 to ll oxic CAUTION to 5000 to 20000 Over 1 ounce to 1 pint or 1 pound III Slightly More More than Greater than I O 1 t 1 d Toxic CAUTION than 5000 20000 20 M pm or poun Toxicity Categories for Pesticides H d Wquot I II III IV Indicators p to and Greater 0ral LD50 including 50 From 50 through 500 mgkg 500 mrough 5 000 than 5000 mgkg g g39 mgkg Inhalation Up to and Greater F 20 th 200 LC a Dust including 20 mgl From 20 through 20 mgl rough than 200 or mist g 39 mgl Inhalation Up to and Greater F 2 000 th h LC b Gas including 200 pm From 200 through 2000 pm 230310 m mug than 20000 or vapor p 39 pm Up to and Greater F 2 000 th h Dermal LD50 including 200 From 200 through 2000 mgkg mm mug than 20000 20000 mgkg mgkg mgkg Irreversible Corneal opacity reversible within 7 No corneal opacity N0 Eye effects corneal opacity at days or irritation persisting for 7 irritation reversible within irritation 7 days days 7 days 39 Severe irritation or No M39ld 139 ht 39 39tat39 t Skin irritation damage at 72 Moderate irritation at 72 hours 721h00 1g II Ion a irritation at hours u 39 72 hours 1 Cardiovascular health A the heart is a pump made out of muscle 1 looks like an upsidedown pear about the size of your fist resides in the pericardial cavity wk 4 U more than a gallonminute 2000 gallonsday a behind breastbone b center of chest between the lungs three layers of tissue a epicardium b myocardium c endocardium thin outer layer the middle layer consisting of the heart muscle itself inner layer four chambers a atrium upper chamber receives blood from the veins b ventricle lower chamber c connected by valves d blood ows in one direction blood ow a unoxygenated blood enters the right atrium b from right atrium into the right ventricle c right ventricle pumps blood into lungs via the pulmonary artery d oxygenated blood ows into the left atrium e from left atrium into the left ventricle 1 left ventricle is an extremely power Jl pump 2 blood is pumped through the aorta and to the rest of the body f pumping is controlled by the nervous system 1 epinephrine and norepinephrine stimulate beating 2 these stress hormones are released from anger or fear B the circulatory system 1 network of blood vessels LN a bring oxygen and nutrients to the organs and tissues and carry away wastes b reaches every cell in the body c carries hormones antibodies white blood cells d approximately 100000 miles long three types of blood vessels a arteries carry oxygenated blood from the heart b capillaries are small vessels that bring blood directly to cells c veins carry unoxygenated blood back to the heart blood is the uid that travels through the heart and the circulatory system a plasma yellowish liquid that carries other blood components b erythrocytes red blood cells 1 contain hemoglobin 2 carries oxygen c leukocytes white blood cells 1 part of the immune system 2 destroy invading microbes d platelets small bodies that patch damage in the walls of blood vessels 1 form clots along with clotting factors 2 prevent us from bleeding to death e blood is continuously being synthesized 1 mostly in bone marrow 2 some WBC called lymphocytes are manufactured in the lymphatic system C cardiovascular disease 1 major forms are coronary heart disease CHD hypertension rheumatic fever 0quot congenital heart disease and stroke CHD a blood ow to the heart is insu icient to supply oxygen and nutrients b usually results from arteriosclerosis hardening of the arteries atherosclerosis most common form of arteriosclerosis plaque fatty deposits build up inside arteries and restrict blood ow in CHD plaques form in coronary arteries going to the heart if a blood clot thrombus forms it can block the ow of blood to the heart resulting in a heart attack e if the blood ow to the brain is blocked the result can be a stroke 90 Us myocardial infarction medical term for heart attack a infarct area of dead or dying tissue b heart muscle is dying from lack of blood ischemia c brain death can occur within minutes if the heart doesn t pump enough blood CHD affects more than 20 million Americans about 10 of the population signs of a heart attack a intense prolonged chest pain usually described as crushing not sharp 1 like the heart is being squeezed 2 some heart attacks are not accompanied by chest pain b pain extending from the chest to the left shoulder and arm the back sometimes the jaws and gums c prolonged pain in the upper abdomen d shortness of breath e fainting or weakness f heavy perspiration nausea or vomiting g anxiety and fear angina pectoris choke chest a angina chest pain similar to but less severe than a heart attack b pain is below the breastbone and may extend to the left jaw and shoulder down the left arm c can be mistaken for heartburn or indigestion d symptom of restricted blood ow to heart 1 usually occurs during periods of exertion 2 can occur during sleep exposure to cold or strong emotion e attacks can last several minutes and are usually relieved by rest f nitroglyerine can open coronary arteries increasing blood ow to heart g h no lasting damage to heart many but not all heart attacks are preceded by angina 8 hypertension high blood pressure a can lead to heart attacks congestive heart failure kidney damage stroke even blindness b blood pressure 1 systolic pressure when heart contracts 2 diastolic pressure pressure when heart is between beats 3 normal 12080 mm Hg 4 hypertension at least 140 systolic or 90 diastolic c accelerates atherosclerosis d damage can occur over a long period of time 9 congestive heart failure a damage prevents heart from pumping out all the blood it receives b blood backs up or pools in veins lungs or lower extremities c can result from a congenital condition loss of muscle heart attack or disease rheumatic fever high blood pressure d signs 1 edema swelling especially in ankles and legs 2 shortness of breath 3 loss of muscular endurance e usually treatable 1 exercise to strengthen heart 2 proper diet 3 weight control 4 avoidance of alcoholic beverages 5 drugs a diuretics to decrease edema b digitalis increase heart contractions c vasodilators expand the arteries making it easier to pump blood 10 rheumatic fever a b c in ammatory disease accompanied by fever that can damage the heart or kidneys caused by an autoimmune reaction to Streptococcus heart valves may become in amed causing permanent damage 11 congenital heart defects a b C d 12 arrhythmias a b c the heart or connections between the heart lungs and blood vessels fail to develop normally most common type of birth defect cause is generally unknown but some are due to a viral infection like rubella treatment usually requires surgery and may completely fix the problem abnormal heartbeat or rhythm common and usually unnoticed tachycardia sudden acceleration of heartbeat to around 160 beatsminute ventricular fibrillation ventricles contract irregularly and pump ineffectively 1 cause of most heart attack deaths 2 can be stopped with a de brillator 3 ventricular brillation can trigger cardiac arrest where the heart stops beating completely a loss of consciousness b cessation of breathing c death d CPR cardiopulmonary resuscitation may restart the heartbeat of someone in cardiac arrest 13 stroke cerebrovascular accident CVA a occurs when blood ow to part of the brain is obstructed b three types of strokes 1 cerebral thrombosis a most common b blood clot thrombus blocks a cerebral artery c enhanced by atherosclerosis 2 cerebral embolism a a blood clot or other particle forms in another part of the body travels through the circulatory system and lodges in an artery that serves the brain b emboli usually form in the heart from atrial fibrillation 3 hemorrhagic stroke a least common but most severe stroke b 50 death rate c a blood vessel in the brain ruptures leaking blood into brain cavities d often linked to high blood pressure i can occur with a head injury ii could be due to a burst aneurysm blood filled sac that balloons out from a weakened portion of an arterial wall c typical effects of stroke are slurred speech blurry vision loss of feeling sudden loss of consciousness severe headaches II Diagnosis and treatment of cardiovascular disorders A diagnostic tests 1 stethoscopes can detect heart irregularities a heart murmurs occur when blood passes through a valve that s normally closed b irregular rhythms 2 blood tests a cholesterol b thyroid hormones overactive thyroid linked to some arrhythmias c sugar levels high sugar may indicate diabetes a major risk factor for CHD 3 electrocardiogram ECG or EKG a heart s electrical activity b EKG reveals abnormal heart rhythms c stress tests with physical activity while EKG monitored d Holter monitor portable EKG worn 24 hours day echocardiogram uses ultrasonic imaging to visualize heart radionuclide imaging allows viewing how blood ows through the heart UIJgt 7 magnetic resonance imaging MRI a uses magnets to generate a computerized image of body parts b can detect heart damage from previous heart attacks or abnormalities in the blood vessels around the heart coronary angiography angiogram a cardiac catherization catheter is inserted into heart through the aorta b dye is injected into the heart to visualize plaque within coronary arteries electroencephalogram EEG measures brain waves and can reveal abnormal brain activity indicating damage computerized axial tomography smn CAT scan a specialized Xray machine that takes pictures from several angles and constructs a 3D image b can help determine if a stroke was caused by a thrombus or hemorrhage c blood thinners are appropriate for clots but dangerous with hemorrhages B treating heart disease 1 2 3 4 5 medication a thrombolytic agents e g streptokinase can dissolve blood clots b betablockers reduce pumping demands on the heart c vasodilators expand blood vessels increasing ow to heart d drugs to lower blood cholesterol coronary bypass a a vein from another part of the body is used to bypass a clogged coronary artery b bypass can eventually become clogged balloon angioplasty percutaneous transluminal coronary angioplasty a catheter is threaded to blockages a balloon is in ated to atten the blockage against the artery wall in an atherectomy blockages are surgically removed or cleared with a laser blockages commonly reoccur e some procedures leave a stent in place transplants a very risky due to nature of surgery and risk of rejection b about 80 survival after one year pace maker a electrical device about the size of a silver dollar b transmits electrical impulses to maintain a normal heartbeat P 9 111 Risk factors A uncontrollable age a risk of CHD rises sharply with men after about 40 b slow rise with women until menopause then a rapid increase c stroke usually occurs after age 65 gender a men at greater risk than women b risk seems to even out around age 65 heredity US a close male relative who had a heart attack before 55 b female relative before 65 4 race ethnicity a African Amerimns are about 75 more likely to die from CHD than white Americans b African Americans are about 60 more likely to suffer strokes than white Americans 1 linked to hypertension 2 may involve economic differences controllable 1 hypertension 2 cholesterol a LDL low density lipoproteins cling to artery walls b HDL carries excess cholesterol to the liver for elimination c values should be less than 200 mgdL 1 HDL should be at least 35 mgdL 2 LDL should not exceed 160 mgdL 3 triglycerides a dietary fat in bloodstream b risk of CHD with value of 250 mgdL 1 increases risk of heart disease 2 associated with obesity and high cholesterol 4 diabetes mellitus a damages blood vessels b accelerates atherosclerosis c contributes to hypertension 5 obesity a associated with other risk factors b apples at greater risk than pears 6 smoking a more than doubles the risk b increases cholesterol while lowering HDL c risk can be eliminated within two years of quitting 7 inactivity 8 personality type A behavior 9 emotional arousal a high levels of anger or anxiety can damage the cardiovascular system b increased risk of hypertension c mental stress can decrease blood ow to heart 10 environmental stress a regular routine helps b calming surroundings