NURS 350 - Pathophysiology (PDF)

it keek 5 : Infection , Stress & Disease , Cancer...

it keek 5 : Infection , Stress & Disease , Cancer Biology Chapter 70 : Infection Infection is the invasion and multiplication of microorganisms in the body tissues that cause disease => For it must infection to occur, interfere with a person , pathogen, and. environment => disease death and due to infectious significant morbidity : causes - Emergence of infections. new · Reumergence of unknown infections. · · Development of antibiotic resistant infections - * most deaths related to infections are found in immunocompromised people (children , elderly , chronic illnesses). Microrganism and Humans survival Body · can compatible for pathogens be Mutual symbiotic relationship · · Normal microbiome - Resident microorganisms are found in diff-parts of the body. - Produces enzymes that help digestion. Produces antibacterial factors - - Produces metabolites (vitamin K and B vitamins)  Factors for Infection D Communicability-ability to spread disease from to others one. 2) Infectivity-ability of pathogen to invade and multiply in host - 3) virulence Capacity - pathogen to cause severe disease of. # Pathogenicity Ability of an agent to produce disease. - 5 Portal of entry-route by which pathogenic microorganism infects host. 6) Toxigenicity Ability to produce soluble toxins or endotoxins factors - , that influence pathogen's virulence. Process ofInfection a. Transmission-infections microorganisms are transmitted by (direct indirect droplet/airborne vertical/hor-trans) , , , Colonization 6 - Ability of pathogen to survive and multiply - or on within the human - environment c Invasion Invades surrounding tissues by evading host's defenses.. - d Dissemination. - Spread of infection by direct extension through surrounding tissue , blood , or lymphatic vessels e. Cell/Tissue damage - may occur directly by lysis or toxin prod. by an immune response. - Tissue damage enhances pathogenicity of the organism. Stages of Infection Incubation - period from initial exposure to onset of first symptoms. Prodromal - occurence of initial symptoms usually mild (discomfort tired) Famil , Invasion-mores and body tissues. farther affects other and Convalescence recovery occurs symptoms decline or the disease - , is fatal , or has a period of latency. infectious to others. * Infection is usually dependent on adequate numbers of microorganisms the host's rather than a compromise of defenses. Classification of Infections · Infections disease is spread from person to person · Endemic relatively high but constant rates of infection Diseases with , , in particular population a. Epidemic · Number of new infections in particular population that greatly a exceeds the number usually observed. · Pandemic An that epidemic spreads over a large area such as a continent or worldwide. Pathogenic Defense Mechanism disease by pathogens successfully cause : - a. Compete with normal flora b. Produce toxins Produce enzymes c to avoid phagocytosis opsonization destroy , , connective tissues d Avoid lysis-stop complement cascade by degrading 236. e Paralyze ciliary activity. Produce f biofilms to protect from immune cells/antibiotics..  BACTERIAL INFECTION - Bacteria is prokaryotic , ine no discreet nucleus. Important factors in infection include helping bacteria cause - - : Fron needed to multiply (siderophores iron receptors) · - presence of polysaccharide capsules · Suppression of complement activation · Bacterial rates proliferation surpassing protective response · => Bacteremia (presence) or Septicemia (growth) * Sepsis can lead to shock and vascular compromise. · Bacteria present in blood bacteria-releases toxins Gram-negative · * Endotoxins LPS found in cell wall bacteria, or of gram-neg released when bacteria cell wall is lysed. · Failure of the body's defense mechanism. · Endotoxins released in blood activate complement and clotting systems- ↳ capillary permeability causes plasma to escape into surrounding tissues producing widespread hypotension ; severe cases= cardiovascular shock. · staphylococcus aureus nosocomial major causes of hospital or infection life threatening - , common on skin and nasal passages. - - opportunistic , secretes endotoxins - Antibiotic resistance is a major problem.  Toxin production · A) Exotoxins Creleased microbe) from living Enzymes that damage host cell plasma membranes or can · inactivate critical to protein synthesis. enzymes B) Endotoxins Creleased LPS) from lysed gram-negative bacteria : Activate inflammatory response and produce fever. · · GRAM-NEGATIVE BACTERIA - Do not retain crystal violet dye in Gram staining process. Thin LPsCendotoxin), peptidoglycan layer and outer membrane with - phospholipids proteins , · GRAM-POSITIVE BACTERIA Retains crystal violet dye in staining - gram process. and Thick peptidoglycan layer with reichoic lipoteichoic - acids. LPS Effects : - Low Quantities - monocyte activation endothelial cell , activation activation , complement Crocal inflammation) Moderate Quantities - Fever (Brain) , Acute-phase reactant CLiver) , Leucocytes (Bone) (systemic Effects High Quantities : - Low cardiac output and peripheral resistance , blood vessel ARDS injury , [Septic shock)  CLINICAL MANIFESTATIONS OF INFECTIONS DISEASE - Variable, depends on pathogen · caused directly by pathogen , or indirectly by its products · Fatigue , malaise , weakness , loss of concentration , generalized aching loss of appetite ,. - Fever Hallmark of infection · Exogenous pyrogens-outside of host · Endogenous pyrogens-made by host inflammatory response. · COUNTERMEASURES AGAINST BACTERIAL PATHOGENS · Antibiotic resistance Horizontal gene transfer · inactivation Enzymatic antibiotics · of · Aminoglycoside-modifying enzymes CAmEs) Multi-drug resistant transporters (MDRs) · - Proteins that prevent antibiotic cell access Target bypass Cresistance mechanism) · => Methicillin-resistant Staphylococcusaureus (MRSA) - International health crisis overuse of antibiotics/not completing antibiotic regimen - - Fusidic acid : binds to ribosome and prevents proton synthesis old treatment revisited : bacteriophages - viruses that infect bacteria. - - Produces beta lactamase  FUNGAL INFECTIONS - Large microorganisms with thick , rigid cell walls - Mold yeast dimorphic , , - Eukaryotic - Disease caused by fungi : Mycosis - Transmitted by inhalation or contamination of wounds. - Dermatophytes if infection invade skin hair or nails , , - Systemic infection is usually from immunosuppression - Pneumocystis Carinic was reclassified as fungus and named a P. jirorecii - Adapt to host environment (wide temp variations, low. oxygen , MptD - suppress immune defenses => Candida albicans - most common fungal infection - found on skin, GI tract , mouth , raging - Local defense mechanisms and microbiome produce antifungal agents - Remains localized of : Immune is intact system · · Immune system is compromised , then infection can become systemic.  PARASITIC AND PROTOLOAN INFECTIONS Parasitic => infections · Toxoplasma gondii Trichomonas Vaginalis · => Protozoan Infections Transmitted through rectors : - · Malaria by mosquitoes Trypanosomes by fly tsetse · Leishmania spp by sand flies · - contaminated water food Cardia lambia) Others found in · or VIRAL INFECTIONS Most - common afflictions of humans - Viruses are intracellular parasites ; replication depends on ability host cell. to infect - self-limiting. Do not have any metabolic organelles necessary for reproduction - · Replicates by taking over the metabolic systems of host cell May Kill cell, coexist with cell be killed or by immune · , system. - Transmission : aerosol , infected blood sexual contact rector- , , - rarely produce Viruses toxins Viral infection symptoms are mild (ever aches nausea - , , , hantavines Some viruses rapidly proliferate (norovirus rotorious ebola marburg, - , , , Interferons effective against many viruses are - - Viruses are sensitive to complement activation.  Life Cycle of Viruses : - completely intracellular · Translation of mRNA results in the production of viral proteins. budding For enveloped viruses , virious released through. · new are host cell and transmitted Viral DNA is integrated in the to · daughter cells by mitosis. => Harmful Effects Viruses of · Inhibition DNA RNA or protein synthesis of , Disruption lysosomal membranes · of Promotion of cell apoptosis · Fusion of adjacent cells (giant cells) · Transformation into cancer cells · cells) Alteration of antigenic properties Cimmune attacks normal · => Stages of Viral Infection · Attach to host cell via protein receptors · Penetrates host cell · releases genetic information into host cytoplasm uncoating - - RNA viruses enter host nucleus - produce mRNA HIV may produce provirus DNA Cretoviruses - : - DNA viruses enter host nucleus - may integrate into host DNA or may make mRNA - => Viral Replication Translationof mRNA results in the production of viral proteins. · Assembly of new virions are released through budding. · · Viral DNA is integrated in host cell - DNA is transmitted to daughter cells by mitosis. # IV and AIDS AIDS caused viral HIV is by · Depletes the helper (Th) cells body's T - HIV is a form of secondary immunodeficiency. - is susceptible to life-threatening infections and - cancer. - Incidence : ↳ Worldwide : is and remains and a major cause of morbidity mortality ; Africa is the epicenter of the AIDS pandemic - - At the end 2020 estimated 37 7 million living with HIV of. , globally- ↳ United States : - 1 million > are living with HIV · New and infections declining or stable most racial · are in ethnic groups. New increased 30% American Indian and · infections > in Alaska Native populations. 2 Types of HIV : - · * HIV-1 HIV in US Western Central and South America (most commons cause Europe : of - , , * HIV-2 : -cause of South and India Cless common/less HIV in Africa infectious) made disease- Effective antiviral therapies have AIDS chronic · a · Blood-borne pathogen (blood , vaginal fluid , semen , breast milk) · Routes transmission blood blood products IV drug use, sexual activity, of or - , maternal-child transmission before or during birth. => HIV : Mechanism of Enjury · Retrovirus (RNA) Genetic information is in the form of RNA - Cstores genetic material on single-stranded RNA rather than usual double-stranded DNA) - contains reverse transcriptase to convert RNA and creates a double stranded DNA version of the virus. Integrase inserts new DNA into infected cell's genetic material - ↳ May be dormant no problems develop : ↳ May activate many problems develop : - New DNA becomes and accelerates part cell's genetic material - of and apoptosis shedding of infectious HIV => HIV Structure gp120 protein binds to the CD4 molecule found primarily surface of helper T cells. · on (Typically CD4 : CD8 ratio) + Destroys CD4 Th cells 800 to 1000 cells/mm3 Reverses - , , Co-receptors · - CXCR4 and CCR5 (strains can be selective for these receptors , influences the tropism cells). of the target Clinical => manifestations of HIV Serologically negative serologically positive but asymptomatic early - , , Stages of HIV or AIDS , kindow period infectious but asymptomatic :. - - Th cells 200 cells/mm3 diagnostic for AIDS - Fatigue , headache muscle aches fever, , may be asymptomatic years - for  made => Diagnosis of AIDS is in association with variousclinical conditions and lab tests : Atypical opportunistic infections and - or cancer Presence antibodies of against HIV - - CD4 + T-cell numbers are at or below 200 cells/mL (dependsa => Phases of HIV Disease => Prevention HIV of not made vaccines so very effective : progress is being - far - reduce risk behaviors. => Research on HIV Fusion inhibitors (interferes with HN and CD4+ cells fusion of - - Integrase inhibitors (worked in monkeys to slow disease progression ; - undergone clinical trials) have Entrance inhibitors (co-receptor binding inhibition) - Uses · monodonal antibodies to inhibit binding to co-receptors.