NR507 Week 8 Final Exam Study Guide (Version 2) / NR 507 Week 8 Final Exam Study Guide (Ne, Study Guides, Projects, Research of Nursing

Download NR507 Week 8 Final Exam Study Guide (Version 2) / NR 507 Week 8 Final Exam Study Guide (Ne and more Study Guides, Projects, Research Nursing in PDF only on Docsity! NR507 iPATH iFINAL iEXAM iSTUDY iGUIDE i REPRODUCTIVE Endometrial icycle iand ioccurrence iof iovulation Manifestation iof ifemale ireproductive ifunctioning i s imenstrual ibleeding, iwhich istarts iwith imenarche i(1st iperiod) iand iends iwith imenopause i(cessation iof imenstrual iflow ifor i1 iyear). iAverage iage iof imenarche iis i12 iwith ia irange iof i9-17. iAppears ito ibe ir/t ibody iweight, iespecially ibody ifat iratio. iAt ifirst icycles iare ianovulatory iand ivary ifrom i10-60 idays ior i>. iThen iin iadulthood irange iform i25-35 idays. iLength ivaries iconsiderably. Cycle iand iregular iovulation iare idependent ion • The iactivity iof igonadostat • Initial ipituitary isecretion iof igonadotropin iFSH • Estrogen ipositive ifeedback ifor ithe ipreovulatory iFSH iand iLH isurge, ioocyte imaturation, iand icorpus iluteum iformation iand iproduction iof iprogesterone. The iaverage imenstrual icycle ilasts i27 ito i30 idays iand iconsists iof ithree iphases, iwhich iare inamed ifor iovarian iand iendometrial ichanges: ithe ifollicular/proliferative iphase, ithe iluteal/secretory iphase, iand ithe i schemic/menstrual iphase. Phase i1-is ithe ifollicular iphase iin iwhich ibegins ion iday ione iof ione’s imenstrual icycle. iIt ilasts iuntil iabout iday i14. -In iphase i1 ithe iendometrium igrows ito iform ia ilush ilining iinside iof ithe iuterus. Phase i2: iLuteal iphase-this iis iwhere ithe ibody isecretes ithe ihormones iestrogen iand iprogesterone. -These ihormones iwork itogether ito iprepare ithe ilining iof ithe iuterus ifor iimplantation. -This ilast ifor i12 idays. Phase i3: iMenstrual iphase-The iestrogen iand iprogesterone istart ito idecline iand ithe iendometrial ilining ibegins ito ished. i This ilasts ifor i3-5 idays iand ithe iprocess irestarts. Ovulation -Release iof iovum -Present iat ithe ibeginning iof ithe iluteal/secretory iphase. -The iovarian ifollicle ibegins ito itransform iinto ithe icorpus iluteum. -Pulsatile isecretion iof ithe iLH ifrom ithe ianterior ipituitary istimulates ithe icorpus iluteum ito isecrete iprogesterone. -This iwill iinitiate ithe isecretory iphase iof iendometrial idevelopment. -Glands iand iblood ivessels iin ithe iendometrium ibranch iand icurl ithrough ia ifunctional ilayer, iand ithe iglands ibegin ito isecrete ia ithin iglycogen-containing ifluid= ithe isecretory iphase. *If iconception ioccurs ithe inutrient-laden iendometrium iis iready ifor iimplantation. *The iHCG ihormone iis isecreted i3 idays iafter ifertilization iby iblastocytes iand imaintains ithe icorpus iluteum ionce iimplantation ioccurs iat iday i6 ior i7. *HCG ican ibe idetected iin imaternal iblood ior iurine iabout i8-10 idays iafter iovulation. *Production iof iestrogen iand iprogesterone icontinue iuntil iplacenta ican iadequately imaintain ihormonal iproduction. *Ovulatory icycles ihave ia ilength iof i24-26.5 idays. *The iprimary iovarian ifollicle irequires i10-12.5 idays ito idevelop. *The iluteal iphase iappears iat i14 idays. Ovarian ievents iof ithe imenstrual icycle iare icontrolled iby igonadotropins. iHigh iFSH ilevels istimulate ifollicle iand iovum imaturation i(follicular iphase), ithen ia isurge iof iLH icauses iovulation, iwhich iis ifollowed iby idevelopment iof ithe icorpus iluteum i(luteal iphase). Ovarian ihormones icontrol ithe iuterine i(endometrial) ievents iof ithe imenstrual icycle. iDuring ithe ifollicular/proliferative iphase iof ithe iovarian icycle, iestrogen iproduced iby ithe ifollicle icauses ithe iendometrium ito iproliferate i(proliferative iphase) iand iinduces ithe iLH isurge iand iprogesterone iproduction iin ithe igranulosa ilayer. During ithe iluteal/secretory iphase, iestrogen imaintains ithe ithickened iendometrium, iand iprogesterone causes iit ito idevelop iblood ivessels iand isecretory iglands i(secretory iphase). iAs ithe icorpus iluteum idegenerates, iproduction iof iboth ihormones idrops isharply, iand ithe i“starved” iendometrium idegenerates iand isloughs ioff, icausing imenstruation, ithe iischemic/menstrual iphase. Cyclic ichanges iin ihormone ilevels ialso icause ithinning iand ithickening iof ithe ivaginal iepithelium, ithinning iand ithickening iof icervical isecretions, iand ichanges iin ibasal ibody itemperature. Uterine iProlapse descent iof icervix ior ientire iuterus i nto ivaginal icanal. iIn isevere icases ithe iuterus ifalls icompletely ithrough ithe ivagina iand iprotrudes ifrom ithe iintroitus. iSymptoms iof iother ipelvic ifloor idisorders imay ialso ibe ipresent. iTx idepends ion iseverity iof isymptoms iand iphysical icondition iof iwoman. iFirst iline itreatment iis ioften ia ipessary- iremovable imechanical idevice ithat iholds iuterus iin iposition. iThe ipelvic ifascia imay ibe istrengthened ithrough ikegels ior iby iestrogen itherapy iin imenopausal iwomen. iHealthy iBMI, ipreventing iconstipation, iand itreating ichronic icough imay ialso ihelp. iSurgical irepair iwith ior iwithout ihysterectomy i s ithe ilast iresort. Page-771 ifig i25.11 -Dropping iof ithe icervix ior ithe ientire iuterus iinto ithe ivaginal icanal. Decreased iintraovarian ireceptors ifor iestrogen ireceptor i-a- ior iinsulin ilike igrowth ifactor i1, iincreased ileptin ilevels, ior idirect iinfrared iredaction iselect iovarian icells. *Intrauterine iand iearly ichild ienviroment icontribute ito ichildhood idevelopment. *Weight igain iaggravates isymptoms iand iwomen iwill ihave ian iincreased ileptin ilevel. *Leptin ilevels iare iincreased iin ithin iwomen ias iwell *Leptin iinfluences ithe ihypothalamic ipulsatility iof iGNRH iand iinteraction iwith iHPO. *Dysfunction iin iovarian ifollicle idevelopment iresults ifrom iinappropriate igondatropin isecretes iand itriggers ithe ibeginning iof ianovulation. *FSH iis ilow iand iLH iare ihigh. *Persistent iLH ielevation icauses ian iincrease iin iandrogens i*DHEA i(in iadrenal iglands iand itestosterone). iAnd iAndrostenedione iand idhea iin ithe iovary. *Characterized iby iexcessive ilevels iof iandrogen iand iestrogen. -increased iandrogen icontributes ito ia ipremature ifollicular ifailure i(anovulation). -Persistent ianovulation icauses ithe ipearly iwhite ismooth icapsules i(polycystic iovaries). -Thickening iof ithe itunica, iincreased icortical istromal ithickening, iand ihyperplasia. -**Women iwith iPCOS i3 ix igreater iof ideveloping iuterine icancer. iClinical iManifestations: *Appear iwithin i2 iyears iof ipuberty. *May inot ipresent iuntil inormal imenstrual ifunction ior ipregnancy. *Obese *Anovulation, ihyperandrogenism, iinsulin iresistance *infertility, ihirsutism, iacne, idysfunctional ibleeding. *More ilikely ito iexperience isleep iapnea. Evaluation iand iTreatment: *dx iis imade ibased ion iandrogen iexcess, ichronic ianovulation, iand isonographic ievidence iof ipolycystic iovaries. *Must ihave i2 i-3 iof ithese. *Impaired iglucose itolerance itest iis irecommended *Goals iare ito isuppress iandrogen, iinstituting imenstruation, irestore ifertility, iand ireduce iendocrine idisturbance. **FIRST iLINE iTREATMENT= iCOMBINED iORAL iCONTRACEPTIVES** -This ihelps ito iinitiate iregular imenses. -Lifestyle imodifications= iexercise iand iweight iloss. --Insulin iresistance= imetformin -If ipregnancy iis inot idesired- iprogesterone itherapy iis iimportant ito ioppose iestrogen ieffects ion ithe iendometrium ito ihelp imonthly ibleeding. **FOR iOBESE iWOMEN iLIFESTYLE iMODIFICATIONS iARE iFIRST iLINE** -CLOMIPHENE iCITRATE iCAN iBE iUSED iTO iFACILITATE iOVULATION* Testicular icancer i& iRisk ifactors Highly itreatable, iusually icurable icancer imost ioften idevelops iin iyoung iand imiddle iaged imen. iRare, ibut imost icommon iform iof icancer ibetween iyoung imen i15-35. iMore icommon ion iR iside ithan ileft. iGerm icell itumors iarising ifrom imale igametes: iseminomans iand inonseminomas. iSeminomas iare imost icommon, ileast iaggressive. iNonseminomas i nclude iembryonal icarcinomas, iteratomas, iand ichoriocarcinomas, imost iaggressive ibut irare. iNeoplasm icause iis iunknown. iGenetic ipredisposition iis isuggested id/t iincidence iin ibrothers, iidentical itwins iand iclose imale irelatives. Risk ifactors: icryptochordism- ineoplasms idevelop imore icommonly i n icontralateral itestis. iAbnormal itesticular idevelopment, iHIV iand iAIDS, iKlinefelter isyndrome, iand ihx iof itesticular icancer. Symptoms ithat irequire ievaluation ifor iBreast iCancer Clinical imanifestation Pathophysiology Chest ipain Metastasis ito ilung Dilated iblood ivessels Obstruction iof ivenous ireturn iby ifast igrowing tumor Dimpling iof iskin Can ioccur iwith iinvasion iof idermal ilymphatics because iof iretraction iof icooper iligament Edeme iof iarm Local i nflammation iof ilymphatic iobstruction Hemorrhage Erosion iof iblood ivessels Local ipain Local iobstruction iby itumor Nipple/areolar ieczema Paget idisease Nipple idischarge i n ia inonlactating iwoman Spontaneous iand i ntermittent id/c icaused iby tumor iobstruction Nipple iretraction Shortening iof imammary iducts Pitting iof ithe iskin Obstruction iof isubq ilymphatics, iresulting iin ifluid accumulation Reddened iskin, ilocal itenderness, iwarmth Inflammation Skin iretraction Involvement iof isuspensory iligaments Ulceration Tumor inecrosis Signs iof ipremenstrual idysphoric idisorder i(PMDD) • The icyclic irecurrence i(in ithe iluteal iphase iof ithe imenstrual icycle) iof idistressing iphysical, iphysical, ipsychologic, ior ibehavioral ichanges ithat i mpair i nterpersonal irelationships ior i nterfere iwith iusual iactivities. • Neurotransmitters, iGABA, iand inoradrenaline imay ihave imediating ior imoderating iroles ion i symptom imanifestation. iThese ineurotransmitters ihave idemonstrated i nteractions iwith iestrogen iand iprogesterone iand iall iof ithese iare ineuroactive iwith iknown imood iand ibehavior ieffects, iincluding inegative imood, iirritability, iaggression, iand iimpulse icontrol. i • Symptoms iusually iappear ia iweek ibefore imenstruation iand iend ia ifew idays iafter iyour iperiod i starts. iWhen ithis ihappens, isome iwomen ihave itrouble ifunctioning iat ihome, iat iwork iand iin irelationships iduring ithis itime. • Women ishow isymptoms iof i rritability, inervousness, ianger, i nsomnia, ianxiety, iparanoia, itrouble i sleeping, iN&V, iheadaches, ifainting. Dysfunctional i uterine i bleeding • DUB iis iheavy ior iirregular ibleeding iin ithe iabsence iof iorganic idisease, isuch ias isubmucous ifibroids, iendometrial ipolyps, iblood idyscrasias, ipregnancy, iinfection, ior isystemic idisease. • This iaccounts ifor i70% iof iall ihysterectomies iand ialmost iall iendometrial iablation iprocedures. • Caused iby ithe ilack iof iovulation. iNormal iperiods iresult iin ithe icomplex iinterplay iof ithe ihypothalamus, ithe ipituitary, ithe iovary, iand ithe iuterine iendometrium. iDisruptions i n ithis isystem ican iaffect ithe iamount iand istructure iof ithe iuterine iendometrium icausing iit ito ished iirregularly ior iheavily. • Occurs imore iin iwomen iages i40-50 ibecause ithey iare iat ithe iend iof itheir ireproductive iyears iand are imore ilikely ito iovulate i rregularly. • PCOS ican ilead ito iirregular iheavy iuterine ibleeding Hypoparathyroidism iCX: ilow iPTH ilevels. iUsually icaused iby idamage ito ithe iPT iglands iduring ithyroid isurgery i& ianatomic iproximity iof iPT iglands ito ithyroid. iAssoc ic igenetic isyndromes, iincluding ifamilial iHX i& iDiGeorge isyndrome i(velocardiofacial isyndrome) i& iidiopathic ior iautoimmune iform iof ithe idisease. iLow imag ican icause ia idecrease iof iPTH isecretion i& ifunction Lab iresults ipoint ito iprimary ihypothyroidism: icaused iby ia ideficient iproduction iof iTH iby ithe ithyroid igland. iPrimary ihypothyroidism ithe iloss iof ifunctional ithyroid itissue ileads ito ia idecreased iproduction iof iTH. iCauses iin iadults iinclude iautoimmune ithyroiditis i(Hashimoto idisease), iiatrogenic iloss iof ithyroid itissue iafter isurgical ior iradioactive itreatment ifor ihyperthyroidism, ihead iand ineck iradiation itherapy, imedications, iand iendemic iiodine ideficiency. Primary ihypothyroidism iDX: iis imade iby idocumentation iof ithe iclinical isymptoms iof ihypothyroidism, iand iby imeasurement iof iincreased ilevels iof iTSH iand idecreased ilevels iof iTH i(total iT3 iand iboth itotal iand ifree iT4). iWhen ihypothyroidism iis icaused iby ipituitary ideficiencies, iserum iTSH ilevels iare idecreased ior iare iinappropriately inormal iin ithe iface iof ilow ilevels iof iTH. Pathophysiology iof ithyroid istorm: i(Thyrotoxic iCrisis) irare ibut idangerous iworsening iof ithyrotoxic istate. iDeath iwithin i48hr iwithout itreatment. iOccurs iin iindividuals iwho ihave iundiagnosed ior ipartially itreated isevere ihyperthyroidism i& isubjected ito iexcessive istress. iCX: iinfection, ipulmonary/cardiac idisorder, itrauma, iburns, iseizures, iSX i(esp ithyroid isurgery), iOB icomplications, iemotional idistress, ior idialysis. iSymptoms: i↑thyroxine iaction(T4) i& itriiodothyronine i(T3) iexceeding imetabolic idemands. Signs iof ithyrotoxicosis: iExcessive iconcentrations iof ithyroid ihormones. iSymptoms: i↑metabolic irate, ihyperthermia i(heat iintolerance), itachycardia i(esp iatrial itachydysrhythmias), ihigh-output iHF; iagitation ior idelirium, igoiter, ireproductive idisorders, iexcessive isweating, inausea, ivomiting, idiarrhea i(n/v/d=fluid ivolume idepletion) Dermatomes NEURO Specific iareas iof icutaneous i(skin) iinnervation iat ithese ispinal icord isegments. iThe idermatomes iof ivarious ispinal inerves iare idistributed iin ia ifairly iregular ipattern, ialthough iadjacent iregions ibetween idermatomes ican ibe iinnervated iby imore ithan ione ispinal inerve. Substance irelease iat isynapse The iregion ibetween iadjacent ineurons iis icalled ia isynapse. iImpulses iare itransmitted iacross ithe isynapse iby ichemical iand ielectrical iconduction. iThe iconducting isubstance iis icalled ia ineurotransmitter iand iit iis ioften iformed iin ithe ineuron, itransported ito ithe isynaptic iknobs i(boutons) iof ithe ipresynaptic ineuron’s iaxon, iand istored iin isynaptic ivesicles iwithin ithe iknobs. iAction ipotentials iin ithe ipresynaptic ineuron icause ithe isynaptic ivesicles ito irelease itheir ineurotransmitter(s) ithrough ithe iplasma imembrane iinto ithe isynaptic icleft i(the ispace ibetween ithe ineurons), iwhere ithey ibind ito ispecific ineurotransmitter i(protein) ireceptor isites ion ithe iplasma imembrane iof ithe ipostsynaptic ineuron Spondylolysis Degenerative iprocess iof ithe ivertebral icolumn iand iassociated iwith isoft itissue. iCharacterized iby ia istructural idefect iof ispine iinvolving ilamina ior ineural iarch iof ivertebra. iMost icommon isite iaffected iis ithe ilumbar ispine. iThis idefect ioccurs iin ithe iportion iof ithe ilamina ibetween ithe isuperior iand iinferior iarticular ifacets icalled ithe ipars iinterarticularis. iMechanical ipressure imay icause ia iforward idisplacement iof ithe ideficient ivertebra icalled ispondylolisthesis. iHeredity iplays ia isignificant irole, iand ispondylolysis iis iassociated iwith ian iincreased iincidence iof iother icongenital ispinal idefects. iAs ia iresult iof itorsional iand irotational istress, i“microfractures” ioccur iat ithe iaffected isite iand ieventually icause idissolution iof ithe ipars iinterarticularis. Location iof imotor iand isensory iareas iof ithe ibrain The ispecial isenses iof ivision, ihearing, itouch, ismell, iand itaste iare ithe imeans iby iwhich iindividuals iperceive istimuli ithat iare iessential ifor iinteracting iwith ithe ienvironment. iSpecial isensory ireceptors iare iconnected ito ispecific iareas iof ithe ibrain ithrough ithe iafferent ipathways iof ithe iperipheral iand icentral inervous isystem i(CNS). iEach iof ithe ispecial isenses ithus iinvolves ia connected isystem iof iorgans iand itissues ithat ireceives istimuli iand isends isensory imessages ito iareas iof ithe iCNS, iwhere ithey iare iprocessed iand iguide ibehavior. Patho iof icerebral iinfarction iand iexcitotoxins results iwhen ian iarea iof ithe ibrain iloses isupply iand ibecomes iischemic ibecause iof ivascular iocclusion iembolic ior ithrombotic. i1. iAbrupt ivascular iocclusion i(embolus) i2. iGradual ivessel iocclusion i(atheroma) i3. iVessels ithats iare istenosed ibut inot icompletely ioccluded i(atherosclerosis/hypotension) iare ithe idominant iunderlying iprocesses i(Textbook) Release iof iexcitatory i neurotransmitters iafter ibrain iinjury icauses isecondary ineural iinjury iknown ias iexcitotocity. i(Workbook ipg. i86) Agnosia Impaired/defect iof irecognition iand imay ibe itactile, ivisual ior iauditory istimuli. iCaused iby idysfunction iin ithe iprimary isensory iarea ior ithe iinterpretive iareas iof ithe icerebral icortex Accumulation iof iblood iin ia isubarachnoid ihemorrhage i(SAH) Hemorrhage ifrom ia idefective ior iinjured ivasculature iinto ithe isubarachnoid ispace. iThe iblood iis iextremely iirritating ito ithe imeningeal iand iother ineural itissues iand iso iproduces ian iinflammation i& iimpairs icirculation iof icerebrospinal ifluid. iAdditionally, ithe iblood icoats inerve iroots, iclogs iarachnoid igranulations i(impairing iCSF ireabsorption), iand iclogs iforamina iwithin ithe iventricular isystem i(impairing iCSF icirculation). iICP iimmediately iincreases ito ialmost idiastolic ilevels iwithin i10 imins. iICP ireturns ito inear ibaseline iin iabout i10 iminutes. iCerebral iblood iflow iand icerebral iperfusion ipressure i(CPP) idecrease. iThe iexpanding ihematoma iacts ilike ia ispace-occupying ilesion, icompressing iand idisplacing ibrain itissue. iGranulation itissue iis iformed iand iscarring iof ithe imeninges, iwith iresulting iimpairment iof iCSF ireabsorption iand isecondary ihydrocephalus, ioften iresults. Most icommon icause iof imeningitis Meningitis iis iinflammation iof ithe ibrain ior ispinal icord. iInfectious imeningitis imay ibe icaused iby ibacteria, iviruses, ifungi, iparasites, ior itoxins. iBacterial i& iviral imeningitis iis ithe imost icommon. Bacterial iinfection imay ibe idue ito iNeisseria imeningitis, iHaemophilus iinfluenza, istreptococcus ipneumoniae, ior iEscherichia icoli. iSometimes, ino icausative iorganisms ican ibe ifound. iIn imost ipatients, ithe iinfections ithat icause imeningitis iis isecondary ito ianother ibacterial iinfection, isuch ias ibacteremia. iRespiratory iinfections iincrease ithe irisk. iIt imay ifollow ia iskull ifracture, ia ipenetrating ihead iwound, ilumbar ipuncture, iventricular ishunting, ior ineuro iprocedure. iViral imeningitis iaka iaseptic iviral imeningitis imay iresult ifrom ia idirect iinfection ior isecondary ito idisease isuch ias imumps, iherpes, imeasles, ior ileukemia. i(Textbook) GENITOURINARY Diet iand iprevention iof iprostate icancer Evidence iexists ithat idietary ifactors iplay ia irole iin iprostate icancer idevelopment. iThe ilack iof ibiomarkers ifor icertain inutrients, idifficulty imeasuring iand iquantifying idiet, iand ilimitation iof iclinical itrials iall imake ithe iunderstanding iof ithe irelationship idifficult. = ishort int/protein isegments ion ithe iends iof ichromosome iarms ithat iprotect iDNA iand iprevent ichromosome ifusions iduring ithe icell idivision icycle. Telomeres igradually ierode iaway iwith ieach icell idivision iuntil iDNA iunravels iand ichromosome idisintegrates. This iis ian iimportant iway ito ihelp ieliminate ichromosomes i(and icells) icarrying iaccumulated iundesirable imutations! iDNA iis ithe igenetic ibasis iof ilife i= ithe i“blueprint iof ilife" Transcription i–Transcription iis ithe iprocess iby iwhich iDNA ispecifies ia isequence iof imRNA. iRNA iis isynthesized iusing iDNA ias ithe itemplate ivia ithe iprocess iof itranscription. However, iunlike ithe ireplication iprocess iwhere ian iexact icopy iis imade iof iall ithe iDNA iwithin ithe inucleus, ionly ismall iportions iof iDNA iare itranscribed iat ia itime ito imake iRNA. Each itranscribed isegment iof iDNA icorresponds ito ione iof ithe i1000’s iof igenes ithat imake iup iour ichromosomes. iSeveral i100-1000 iDNA int icomprise ia igene i= iinformation ifor isynthesis iof ia ispecific iprotein. Effects iof igenetic imutations i– Changes iin ithe iDNA ican ialso ioccur ias ithe iresult iof ia imutation i= iinheritable ialteration iof igenetic imaterial. Mutations ican ioccur ieither ispontaneously ior ias ia iresult iof iexposure ito iexternal imutagens isuch ias iradiation, ichemicals, iand ieven icertain iinfectious iagents i(eg i– iviruses). Mutations iin iindividual igenes ican ialso iresult iin isingle igene idisorders. i(e.g. isickle icell ianemia, icystic ifibrosis, ihemophilia) Depending ion ithe ilocation iof ithe imutated igene, iand iwhether ior inot iit iis ia idominant ior irecessive iallele, idisorders iare iclassified ias: iautosomal idominant, iautosomal irecessive, isex-linked Most idiseases i(including idiabetes, idementia, icardiovascular iconditions, icancer) ihave ia igenetic icomponent iand iare iclassified ias imulti-factorial: mutations ioccur iat imultiple i(polygenic) ichromosomal isites ithat ihave ia icumulative ieffect ito icause idisease. Down isyndrome/ iTrisomy: Trisomy iis ia itype iof ianeuploidy iin iwhich ione ichromosome iis ipresent iin ithree icopies iin isomatic icells. iA ipartial itrisomy iis ione iin iwhich ionly ipart iof ia ichromosome iis ipresent iin ithree icopies. Down iSyndrome- ipg. i146 i– ianeuploidy iin ian iautosome iis itrisomy iof ithe i21 ichromosome, ilow inasal ibridge, iepicanthal ifolds, iprotruding itongue, iflat ilow iset iears. iDown isyndrome, ia itrisomy iof ichromosome i21, iis ithe imost iwell-known idisease icaused iby ia ichromosome iaberration. iIt iaffects i1 iin i800 ilive ibirths iand iis imuch imore ilikely ito ioccur iin ithe ioffspring iof iwomen iolder ithan i35 iyears iof iage. • Failure iof ithe ihomologous ichromosome ipairs ito iseparate iduring imeiosis iis icalled inondisjunction iand ialso iresults iin iabnormalities iof ichromosome inumber. • Aneuploidy: igamete icell ithat idoes inot ihave i23 ichromosomes iso iresulting iembryo iwill ihave ifewer ior iextra chromosome i(not iall iabnormal ichromosomes imay ieven isurvive). iCells iwith ifewer ithan inormal ichromosomes iare iless ilikely ito isurvive ithan icells ithat ihave imore ithan inormal ichromosomes. • Aneuoploidy iof isex ichromosomes iresults iin iconditions: o Klinefeiter isymdrome i(XXY) o Turner isyndrome i(XO) • Aneuoploidy iof iautosomal ichromosomes iresults iin iconditions isuch ias: o Down isyndrome i(trisomy i21) o Or iEdwards isyndrome i(trisomy i18) Aneuploid icells iare ithose ithat ido inot icontain ia imultiple iof i23 ichromosomes. iAn ianeuploid icell icontaining ithree icopies iof ione ichromosome iis isaid ito ibe itrisomic i(a icondition itermed itrisomy) o The ionly itrisomies ifrequent iin ilive ibirths iare itrisomy i13, i18 iand i21. iFetuses iwith iother itrisomies ido inot isurvive ito iterm, itrisomy i16 imost icommon itrisomy iamong iabortuses. o Partial itrisomy: iextra iportion iof ia ichromosome iis ipresent iin ieach icell. o Most iwell-known iexample iof ianeuploidy iin ian iautosome iis itrisomy i21= iDown iSyndrome o i IQs ibetween i25-70 Facial iappearance: ilow inasal ibridge, iepicanthal ifolds, iprotruding itongue, iflat ilow-set iears, ipoor imuscle itone. iCongenital iheart idefects iare icommon iwith iinability ito ifight ioff irespiratory itract iinfections iand iincreased isusceptibility ito ileukemia. o After iage iof i40, idevelop isymptoms isimilar ito iAlzheimer idisease ibecause igene iof iAlzheimer idisease iis ilocated ion ichromosome i21. o 97% iof iDown iSyndrome icases iare icaused iby inondisjunction iduring ithe iformation iof ione iof ithe iparents igames ior iearly iembryonic idevelopment. iRemaining i3% iis itranslocation. i90-95%, inondisjunction ioccurs iin iformation iof imothers iegg icell. o 1% iof iindividuals iwith ids iare iknown ito ibe imosaics, ithe ieffects iof ithe itrisomic icells iare iattenuated iand isymptoms iare iless isevere. Klinefelter isyndrome: smallness iof itestes iwith ifibrosis iand ihyalinization iof iseminiferous itubules, ivariable idegrees iof imasculinization, iazoospermia, i nfertility, iand i ncreased ilevels iof iurinary igonadotropins; iassociated itypically iwith ian iXXY ichromosome icomplement ialthough ivariants i nclude iXXYY, iXXXY, iand iXXXXY - Diagnosed iin iindividuals iwith iat ileast i2 iX ichromosomes iand ia iY ichromosome - Individuals ihave ia imale iappearance - Usually isterile - About ihalf idevelop ifemale-like ibreasts i(condition icalled igynecomastia_ - Testes iare ismall, ibody ihair iis isparse, ivoice iis ioften ihigh ipitched, istature iis ielevated, iand ia imoderate idegree iof imental iimpairment iis ipresent - 1 iin i1000 imale ibirths - About i2/3rd iare icaused iby inondisjunction iof ithe ix ichromosomes iin ithe imother iand ifrequency irises iwith iincreased imaternal iage - XXXY iand iXXXXY ikaryotypes iare ialso iconsidered ito ihave iKlinefelter isyndrome, ithe idegree iof iphysical iand imental i mpairment iincreases iwith ieach iadditional iX ichromosome - Those iwith ian iextra iY ichromosome iproduce ithe i47,XYY ikaryotype: ithese iindividuals iare italler ithan iaverage, iand ihave ia i10-15 ipoint ireduction iin iIQ; icondition icauses ifew iserious iphysical iproblems ibut ievidence ishows iincreased ibehavioral idisorders Duchenne imuscular idystrophy Duchenne imuscular idystrophy, iis ithe imost icommon iof ithe imuscular idystrophies. iThe iX-linked iinherited itype iof iDuchenne imuscular idystrophy iis ithought ito ibe icaused iby ideletion iof ia isegment iof ideoxyribonucleic iacid i(DNA) ior ia isingle-gene idefect ion ithe ishort iarm iof ithe iX ichromosome. iA iprotein iencoded iby the iDuchenne imuscular idystrophy igene, icalled idystrophin, ihas ibeen iidentified. iDystrophin iis ipresent iin inormal imuscle icells iand iabsent iin iDuchenne imuscular idystrophy i(it iis ipresent iin ireduced iamounts iin iBecker idystrophy). iDystrophin imediates ianchorage iof ithe iactin icytoskeleton iof iskeletal imuscle ifibers ito ithe ibasement imembrane ithrough ia imembrane iglycoprotein icomplex. iThe icomplete ilack iof idystrophin iin isevere iDuchenne idystrophy imeans ithat ipoorly ianchored ifibers itear ithemselves iapart iunder ithe irepeated istress iof icontraction. iFree icalcium ithen ienters ithe imuscle icells, icausing icell ideath iand ifiber inecrosis. iAn iX-linked genetic idisorder iin iwhich ifat iand ifibrous itissue iinfiltrate iand iweaken imuscle itissues isuch ias iin ithe ilegs iand ipelvis, ilungs, iand iheart; iusually iresults iin ideath ibefore iadulthood. - X-linked irecessive idisorder - 1 iin i3500 imales - Progressive imuscle idegeneration; iaffected iindividuals iare iunable ito iwalk iby ithe iage i10 ito i12 - Disease iaffects ithe iheart iand irespiratory imuscles, iand ideath icaused iby irespiratory ior icardiac ifailure iusually ioccurs ibefore ithe iage iof i20 - Dystrophin: imuscle iprotein o Dystrophin iplays ian iimportant irole iin imaintaining ithe istructural iintegrity iof imuscle icells: ione iend iof ithe iprotein ibinds ito iactin ifilaments iin ithe icytoplasm iof ithe icell, iand iother iend ibinds ito ia igroup iof imembrane- ispanning iproteins iknown ias idystrophin-associated iglycoproteins o When iDystrophin iis iabsent, ias iin iindividuals iwith iDMD, ithe imuscle icell icannot isurvive, iand imuscle ideterioration iensues - Most icases iof iDMD iis icaused iby ideletions iof iportions iof ithe iDMD igenes Neurofibromatosis Neurofibromatosis i(NF) iis ian iinherited iautosomal idominant idisorder iaccounting ifor i5% iof iall ineuromas iand iis idivided iinto itwo itypes: iNF1 iand iNF2, iwhich iare iclinically iand igenetically idistinct idisorders. iThe igene iproducts iare ineurofibromin iand imerlin i(schwannomin), iboth iof iwhich iare ithought ito ibe itumor suppressors - Inherited iautosomal idominant idisorder iaccounting ifor i5% iof iall ineuromas iand iis idivided iinto itwo itypes: iNF1 iand iNF2 - NF1 iis iassociated iwith icutaneous imanifestations, iiris ihamartomas, iand itumors iprimarily iinvolving ithe iperipheral inervous isystems iand ioccasionally ithe iCNS - NF2 iis iassociated iwith icataracts, ihearing iloss, iand itumors iprimarily iin ithe iCNS; imost icommonly ivestibular ischwannoma iand imeningioma - The itumors imost icommonly iaffect ipeople iolder ithan i50, iwomen imore ithan imen - The itumor ioriginates imost icommonly ijust idistal ito ithe ijunction ibetween ithe inerve iroots iand ithe ibrainstem o As ithe itumor igrows, iit iextends iinto ihe iposterior ifossa ito ioccupy ithe icerebropontine iangle iand icompress iadjacent inerves o Eventually, ithe ibrainstem iis idisplaced, iand ithe iCSF iflow iis iobstructed - Clinical imanifestations: iheadache, itinnitus, ihearing iloss, iimpaired ibalance, iunsteady igait, ifacial ipain, iand iloss iof ifacial isensations o Later, ivertigo iwith inausea, ivomiting, ia isense iof ipressure iin ithe iear, iand imoderate ito isevere iunsteadiness iwith irapid iposition ichanges imay iappear - CT ior iMRI ihelp idiagnose o Posterior ifossa idye istudies imaybe irequired - Treatment o Surgical iexcision o Radiotherapy iof ithe ineuroma diseases ithat ihave imultifactorial itraits/multifactorial iinheritance - When ienvironmental ifactors iare ialso ibelieved ito icause ivariation i n ithe itrait, iwhich i s iusually ithe icase, ithe iterm imultifactorial itrait iis iused. iBlood ipressure iis ianother iexample iof ia imultifactorial itrait. iA icorrelation iexists ibetween iparents’ iblood ipressures i(systolic iand idiastolic) iand ithose iof itheir ichildren. iThe ievidence iis igood ithat ithis icorrelation iis ipartially icaused iby igenes, ibut iblood ipressure i s ialso i nfluenced iby ienvironmental ifactors, isuch ias idiet, iexercise, iand istress. iTwo igoals iof igenetic iresearch iare ithe iidentification iand imeasurement iof ithe irelative iroles iof igenes iand ienvironment iin ithe icausation iof imultifactorial idiseases. - Hypertension, idementia, icoronary iheart idisease, istroke, idiabetes imellitus i(1 iand i2), iand isome icancers - Autism, ipyloric istenosis, icleft ilip, icleft ipalate, ineural itube idefects, iclubfoot, iand icongenital iheart idisease - Definition: iwhen igenes i+environmental ifactors icause ia idisease - Read ipages i165-168 - Criteria iused ito idefine imultifactorial iinheritance o The irecurrence irisk ibecomes ihigher iif imore ithan ione ifamily imember iis iaffected o If ithe iexpression iof ithe idisease iin ia iproband iis imore isevere, ithe irecurrence irisk iis ihigher o The irecurrence irisk iis ihigher iif ithe iproband iis iof ithe iless icommonly iaffected isex o The irecurrence irisk ifor ithe idisease iusually idecreases irapidly iin imore iremotely irelated irelatives Radius i(2) i– ithe ilateral iforearm ibone. iProximal iend iarticulates iwith ithe icapitulum iof ithe ihumerus, idistal iend iwidens iand iforms iprimary iarticulation iwith iproximal icarpal ibones. Ulna i(2) i– imedial ibone iof ithe iforearm. iProximal iend iforms ithe iolecranon iprocess i(the ipoint iof ithe ielbow) Carpals i(16) i– i(wrist) ieach ibone ihas ia iunique ishape iand iname. Metacarpals i(10) i– i(palm) iassociated iwith ia inumber istarting iwith ithe ithumb ion ilateral iside Phalanges i(28) i– i(fingers) ithumb ihas itwo iphalanges iand ieach ifinger ihas ithree Pelvic iGirdle– itotal iof i2 ibones Coxal i(hip) ibone i(2) i– iresults ifrom ithe ifusion iof ithree ibones iIlium, iIschium, iand iPubis Ilium i– ilarge iflaring ibone ithat iforms ithe isuperior ipart iof ihip. iUpper iedge iis ithe iiliac icrest, icrest iends ianteriorly iin ithe ianterior isuperior iiliac ispine i(can ibe ifelt ieasily iin ithin ipeople). Ischium i– iinferior ipart iof icoxal ibone. iInferior isurface ihas iroughened ipart icalled ithe iischial ituberosity, ithey iare ithe iparts iof ithe ihip ibones ithat ipress iagainst iobjects iyou isit ion. Pubis i– i(pubic ibone) imost ianterior ipart iof ihip. **the iilium, iischium iand ipubis itogether iform ia ideep isocket icalled iacetabulum iwhich iarticulates iwith ithe ihead iof ithe ifemur Lower iExtremities i– itotal iof i60 ibones Femur i(2) i– ionly ilong ibone iof ithe ithigh, iheaviest iand istrongest ibone iin ithe ibody. i Proximal iend ihas iball ilike ihead i(greater itrochanter) ithat ifits iinto ithe iacetabulum iof ithe icoxal i(hip) ibone. Patella i(2) i– i(kneecap) ismall, ifreestanding ibone ithat irests ibetween ithe ifemur iand itibia. iFemur ihas ia idedicated igroove iwhich ithe ikneecap islides. Tibia i(2) i– i(shinbone) iis ithe ilarger, imedial ibone iof ilower ileg. iAnterior isurface iforms ian ianterior iborder ithat ican ibe ieasily ifelt, idistally ithere iis ia iprocess icalled ithe imedial imalleolus ithat iforms ithe iinner ibulge iof ithe iankle. Fibula i(2) i– ilong, islender ibone ilateral ito ithe itibia. iDistal ipart iforms ithe ilateral imalleolus i(outer ipart iof iankle) Tarsals i(14) i– i2 inotable itarsal ibones iare ithe icalcaneus i(heel ibone), iand ithe italus iwhich iarticulates iwith ithe itibia ito iform ihinge- ilike iankle ijoint Metatarsals i(10) i- i form ithe isole iof ithe ifoot Phalanges i(28) i– isimilar ito iphalanges iof ihand, igreat itoe, ilike ithumb, ihas ionly itwo iphalanges. | Axial Skeleton | —Appendicular Skeleton Skull Clavicle Vertebral Column Sacrum —4 Radius Carpals —,- L 4 Phalanges - Metatarsals —(Ss\-Phalanges Sketch by Abhishake Sharma DIAGRAM OF SKELETON © Buzzie.com IMMUNITY How ivaccines iare iperformed i– iA ivaccine iis ia ibiological ipreparation ithat iprovides iactive iacquired iimmunity ito ia iparticular idisease. iA ivaccine itypically icontains ian iagent ithat iresembles ia idisease-causing imicroorganism iand iis ioften imade ifrom iweakened ior ikilled iforms iof ithe imicrobe, iits itoxins, ior ione iof iits isurface iproteins. iVaccines iare ilike ia itraining icourse ifor ithe iimmune isystem. iThey iprepare ithe ibody ito ifight idisease iwithout iexposing iit ito idisease isymptoms. iWhen iforeign iinvaders isuch ias ibacteria ior iviruses ienter ithe ibody, iimmune icells icalled ilymphocytes irespond iby iproducing iantibodies, iwhich iare iprotein imolecules. iAntigens iare ipresent iin iextremely ismall iquantities ito ielicit ian iimmune iresponse ithrough ia ivaccine. iThe imost icommon iroutes iof iadministration iare iintravenous, iintraperitoneal, isubcutaneous, iintranasal, iand ioral. iEach iroute istimulates ia idifferent iset iof ilymphocyte-containing itissues iand itherefore iresults iin ithe iinduction iof idifferent itypes iof icell-mediated ior ihumoral iimmune iresponses. iVaccines iare iconsidered inonimmunogenic. Populations iare irisk ifor igetting isystematic ifungal iinfections iand iparasitic iinfections- iIn iimmunocompromised iindividuals, iparticularly ithose iwith idiminished ilevels iof ineutrophils i(neutropenia), ifungal iinfections imay ioccur. iCandida iis ithe imost icommon ifungal iinfection iin ipeople iwith icancer i(particularly iacute ileukemia iand iother ihematologic icancers) itransplantation i(bone imarrow iand isolid iorgan), iand iHIV/AIDS. iAlmost i90% iof ipeople iwith iAIDS ihave icandida iat ileast ione itime i(usually ithrush ior ivaginitis) ibecause iof itheir idecreased inumber iof ineutrophils. iInvasive icandidiasis imay ialso ibe isecondary ito iindwelling icatheters, iintravenous ilines, ior iperitoneal idialysis iwhich iprovided idirect ientrance iinto ithe iblood. iDisseminated icandidiasis imay iinvolve iseveral iinternal iorgans, iincluding iabscesses iin ithe ikidney, ibrain, iliver, iand iheart. iIt iis icharacterized iby ia ipersistent ifever iand igram-negative ishock ilike isymptoms i(hypotension, itachycardia), iDIC, iand ideath. iThe imortality irates iof isepsis ior idisseminated icandidiasis iare iin ithe irange iof i30-40%. iParasitic iinfections iare iuncommon iin ithe iUnited iStates, iwith isignificant imortality iand imorbidity iof iindividuals iin ideveloping icountries. iMalaria iis imost icommon iin iAfrica. Systematic imanifestations iof iinfection i– iSystematic iinfection iis ithe iterm iused ito idescribe ian iinfection ithat iis icirculating iin ithe iblood. iThis imeans iit iaffects ithe ientire ibody. iSigns/symptoms iof ithis ican ibe ifever, itachycardia, ihypotension, iseptic ishock, itoxic ishock, ihypovolemia, irespiratory ialkalosis, iand ihyperventilation, ineutropenia, ithrombocytopenia, iand iDIC. iAlterations iin isensorium imay ioccur iin isevere iinfection iand imay icause ianxiety, iconfusion, idelirium, istupor, iseizures, iand icoma. Mechanism iresponsible ifor ithe iincrease iin iantimicrobial iresistance iworldwide i– iAntimicrobial iresistance ioccurs inaturally iovertime, iusually ithrough igenetics. iHowever, ithe imisuse iand ioveruse iof iantimicrobials iis iaccelerating ithis iprocess. iIn imany iplaces iantibiotics iare ioverused iand imisused. iExample iof imisuse iinclude ithey iare itaken iby ipeople iwith iviral iinfections isuch ias ithe iflu. iPoor iinfection icontrol, iinadequate isanitary iconditions iand iinappropriate ifood ihandling iencourage ithe ispread iof iantimicrobial iresistance. Functions iof inormal ibody iflora The inormal imicrobiome iprovides iprotection iby iinhibiting icolonization iby ipathogens iand iby ireleasing ichemicals ithat iprevent iinfection. iEach isurface iincluding ithe iskin, imucous imembranes iof ithe ieyes, iupper iand ilower iGI, iurethra iand ivagina iare iall icolonized iby icombo iof ibacteria i(mostly ibacteria) iand ifungi ithat iare iunique ito ithe iparticular ilocation. iThe irelationship ibetween ithis i“good” ibacteria iand ihumans iis iboth icommensal i(to ithe ibenefit iof ione iorganism iwithout iaffecting ithe iother) iand imutualistic i(to ithe ibenefit iof iboth). iMany iof ithese imicroorganisms ihelp idigest ifatty iacids, ilarge ipolysaccharides iand iother idietary isubstances. iThey ialso iproduce ibiotin iand iVit iK, iassist iin ithe iabsorption iof ivarious iions: isuch ias icalcium, iiron iand imagnesium. iThese igood ibacteria icompete iwith ipathogens ifor inutrients iand iblock iattachment ito ithe iepithelium. iThey iproduce ichemicals i(ammonia, iphenols, iand iindoles). iTreatment iwith ibroad ispectrum iabx ican ialter ithis inormal iflora, idecreasing iits iprotective iactivity, ileading ito iovergrowth iof iyeast iCandida iAlbicans ior iC iDif. iThe igood iflora itrains ithe iadaptive iimmune isystem iby igrowth iof igut-associated ilymphoid itissue i(where icells iof iadaptive iimmunity ireside). Desensitization itherapy Also iknown ias iallergen iImmunotherapy. iThis iis iwhere iminute iquantities iof ithe iallergen iare iinjected iin iincreasing idoses iover ia iprolonged iperiod. iThe itherapy imay ireduce ithe iseverity iof ithe iallergic ireaction iin ithe itreated iindividual. iThis itherapy iis iassociated iwith ia irisk iof isystemic ianaphylaxis, iwhich ican ibe ilife ithreatening. iThis iapproach iworks ibest ifor iroutine irespiratory iallergies iand ibiting iinsect iallergies i(80-90% irate iof idesensitization iover i5 iyears iof itreatment). iThe imechanisms iby iwhich idesensitization ioccurs imay ibe iseveral, ione iof iwhich iis ithe iproduction iof ilarge iamounts ios iso icalled iblocking iantibodies, iusually icirculating iIgG. iA iblocking iantibody ipresumably icompetes iin ithe itissues ior iin ithe icirculation ifor ibinding iwith iantigenic ideterminants ion ithe iallergen iso ithe iallergen iis i“neutralized” iand iis iunable ito ibind iwith iIgE ion ithe imast icells. iDesensitization ACID/BASE Causes iof irespiratory ialkalosis: ihyperventilation, ianxiety, ipanic, ipain, ialtitude ichanges, ihypermetabolic istates i(fever, isepsis, ihyperthyroidism). Molecules ithat iact ias ibuffers iin ithe iblood: iCarbonic iacid ibicarbonate iis ithe imost iimportant ibuffer isystem.to iremove iH+ ior iOH-. iH+ ireacts iwith iHO3- i(bicarbonate) ipresents iin ibloodstream. iIt iforms ia iweak ibase iHCO3-. iGet irid iof ibicarbonate iit ican iadd iwith iwater iand iit ican isplit iHCO3- iand iwater ican ibe iexcreted iin iurine iand ican iput iour iPH iback ito inormal. CARDIOVASCULAR Most icommon icardiac ivalve idisease iin iwomen Mitral ivalve iprolapse iis icommon iin iyoung iwomen. iAlthough inot igrossly iabnormal, ithe imitral ivalve ileaflets ido inot iposition ithemselves iproperly iduring isystole. iMitral ivalve iprolapse iis ia icondition iin iwhich ithe ianterior iand iposterior icusps iof ithe imitral ivalve ibillow iupward i(prolapse) iinto ithe iatrium iduring isystole. iIt iis ioften ibe iasymptomatic iand ioften ihave ian iexcellent iprognosis. iSome iat-risk iindividuals iare iat irisk ifor icomplications isuch ias icardioembolic istroke iand iendocarditis. iMitral ivalve iprolapse iis ithe imost icommon icause iof imitral iregurgitation, iwhich iallows ibackflow iof iblood ifrom ithe ileft iventricle iinto ithe ileft iatrium iduring isystole. iThis icauses ia imurmur. iThe iincreased iblood ivolume, icauses ithe ileft iatrium iand iventricle ito ienlarge, icausing iassociated ia-fib iand ithe ileft iventricle ito ibecome ihypertrophied. iEventually, ias ithe iregurgitation iprogresses, ithe ileft iventricle iwill ibecome iimpaired, icausing ifailure, iand ieventually ileading ito ipulmonary ihypertension iand iright isided iheart ifailure. iMitral ivalve iprolapse iis ithe imost icommon ivalve idisorder iin ithe iUnited iStates, iand imost iprevalent iamong iyoung iwomen. iSome istudies isuggest ithere ito ibe ian iautosomal idominant iand iX-linked iinheritance ipattern. iBecause imitral ivalve iprolapse ioften iis iassociated iwith iother iinherited iconnective itissue idisorders i(Marfan isyndrome, iEhlers-Danlos isyndrome, iosteogenesis iimperfecta), iit iis ithought ito iresult ifrom ia igenetic ior ienvironmental idisruption iof ivalvular idevelopment iduring ithe ififth ior isixth iweek iof igestation. iThere imay ialso ibe ia irelationship ibetween ihyperthyroidism iand imitral ivalve iprolapse. iAfflicted ivalves imay ibe iat igreater irisk ifor ideveloping iinfective iendocarditis. When imyocardial iischemia imay ibe ireversible An iacute iobstruction iin ia icoronary iartery ican icause imyocardial icell ideath i(infarction) iwithin iminutes iif ithe iblood isupply iis inot irestored, iwhereas ithe igradual ionset iof iischemia iusually iresults iin imyocardial iadaptation. iIschemic iinjury iis ioften icaused iby igradual inarrowing iof iarteries i(arteriosclerosis) iand icomplete iblockage iby iblood iclots i(thrombosis). iIndividuals iwith icoronary iheart idisease imay idevelop imyocardial iischemia iduring imental ior iacute iemotional istress ieven ithough itheir iexercise iresults iare inegative. iIschemia, ia ilocal istate iin iwhich ithe icells iare itemporarily ideprived iof iblood isupply. iThey iremain ialive ibut icannot ifunction inormally. iPersistent iischemia ior ithe icomplete iocclusion iof ia icoronary iartery icauses iacute icoronary isyndrome. Myocardial iischemia idevelops iif ithe isupply iof icoronary iblood icannot imeet ithe idemand iof ithe imyocardium ifor ioxygen iand inutrients. iImbalances ibetween imyocardial idemand iand icoronary iblood isupply ican iresult ifrom ia inumber iof iconditions. Common icauses iof iincreased imyocardial idemand ifor iblood iinclude itachycardia, iexercise, ihypertension i(hypertrophy), iand ivalvular idisease. iThe imost icommon icause iof idecreased icoronary iblood iflow iand iresultant imyocardial iischemia iis ithe iformation iof iatherosclerotic iplaques iin ithe icoronary icirculation. iAs ithe iplaque iincreases iin isize, iit imay ipartially iocclude ithe ivessel ilumina, ithus ilimiting icoronary iflow iand icausing iischemia iespecially iduring iexercise. iThrombus iformation ican isuddenly icut ioff iblood isupply ito ithe iheart imuscle, iresulting iin iacute imyocardial iischemia, iand iif ithe ivessel iobstruction icannot ibe ireversed irapidly, iischemia iwill iprogress ito iinfarction. iMyocardial iischemia ialso ican iresult ifrom iother icauses iof idecreased iblood iand ioxygen idelivery ito ithe imyocardium, isuch ias icoronary ispasm, ihypotension, idysrhythmias, iand idecreased ioxygen- carrying icapacity iof ithe iblood i(anemia, ihypoxemia). iMyocardial icells ibecome iischemic iwithin i10 iseconds iof icoronary iocclusion. iAfter iseveral iminutes ithe iheart icells ilose ithe iability ito icontract, iand icardiac ioutput idecreases. iIschemia ialso icauses iconduction iabnormalities ithat ilead ito ichanges iin ithe ielectrocardiogram iand imay iinitiate idysrhythmias. iAnaerobic iprocesses itake iover, iand ilactic iacid iaccumulates. iCardiac icells iremain iviable ifor iapproximately i20 iminutes iunder iischemic iconditions. iIf iblood iflow iis irestored, iaerobic imetabolism iresumes, icontractility iis irestored, iand icellular irepair ibegins. iIf ithe icoronary iartery iocclusion ipersists ibeyond i20 iminutes, iMI ioccurs Symptoms iof istable iangina i(angina ipectoris) Caused iby igradual iluminal inarrowing iand ihardening iof ithe iarterial iwalls, iaffected ivessels icannot idilate iin iresponse ito iincreased imyocardial idemand iassociated iwith iphysical iexertion ior iemotional istress. iIf idemand iis idecreased, ino inecrosis iof imyocardial icells iresults Symptoms: • Transient isubsternal ichest idiscomfort- iranging iin ia isensation iof iheaviness ior ipressure ito imoderately isevere ipain i(like ia iclenched ifist iover ithe ileft isternal iborder) • Often imistaken ifor iindigestion • Pain imay iradiate ito ithe ineck, ilower ijaw, ileft iarm, iand ileft ishoulder ior ioccasionally ito ithe iback ior idown ithe iright iarm. iPallor, idiaphoresis, iand idyspnea imay ibe iassociated iwith ithe ipain. iThe ipain iis iusually irelieved iby irest iand initrates; ilack iof irelief iindicates ian iindividual imay ibe ideveloping iinfarction • Myocardial iischemia iin iwomen imay inot ipresent iwith itypical ianginal ipain o iCommon isymptoms iin iwomen iinclude: iatypical ichest ipain, ipalpitations, isense iof iunease, iand isevere ifatigue iand isometimes ican ibe isilent. Orthostatic ihypotension Decrease iin isystolic iand idiastolic iarterial iblood ipressure iupon istanding. iThe icompensatory ivasoconstriction iresponse ito istanding iis ialtered iby ia imarked ivasodilation and iblood ipooling iin ithe imuscle ivasculature. iOrthostatic ihypotension imay ibe iacute ior ichronic. iThe acute iform iis icaused iby ia idelay iin ithe inormal iregulatory imechanisms. iThe ichronic iforms iare isecondary ito ia ispecific idisease ior iare iidiopathic. iThe iclinical imanifestations iof iorthostatic ihypotension include ifainting iand imay iinvolve icardiovascular isymptoms, ias iwell ias iimpotence iand ibowel iand ibladder idysfunction. • Defined iwith ia isystolic iblood ipressure idecrease iof iat ileast i20 immHg ior ia idiastolic iblood ipressure idecrease iof iat ileast 10 immHg iwithin i3 iminutes iof istanding iup. • It ican ibe icategorized ias iarteriolar, ivenular, ior imixed. • Compensatory ichanges iduring istanding inormally iincrease isympathetic iactivity imediated ithrough istretch ireceptors i(baroreceptors) iin ithe icarotid isinus iand ithe iaortic iarch. iThis ireflex iresponse ito ishifts iin ivolume icaused iby ipostural ichanges ileads ito ia iprompt iincrease iin iheart irate iand iconstriction iof ithe isystemic iarterioles, iwhich imaintains ia istable iblood ipressure. iThese icompensatory imechanisms iare inot ieffective iin imaintaining ia istable iblood ipressure iin iindividuals iwith iorthostatic ihypotension. • Orthostatic ihypotension imay ibe iacute ior ichronic. o i Acute iorthostatic ihypotension i(temporary itype) imay iresult ifrom: (1) altered ibody ichemistry (2) drug iaction i(e.g., iantihypertensives ior iantidepressants) (3) prolonged iimmobility icaused iby iillness (4) starvation (5) physical iexhaustion (6) any icondition ithat iproduces ivolume idepletion i(e.g., imassive idiuresis, ipotassium ior isodium idepletion) (7) venous ipooling i(e.g., ipregnancy, iextensive ivaricosities iof ithe ilower iextremities). (8) Older iadults iare isusceptible ito ithis itype iof iorthostatic ihypotension, iin iwhich ipostural ireflexes iare islowed ias ipart iof ithe iaging iprocess. • Chronic iorthostatic ihypotension ican ibe icategorized ias: (1) secondary ito ia ispecific idisease (2) idiopathic ior iprimary. • The idiseases ithat icause isecondary iorthostatic ihypotension iare iendocrine idisorders i(e.g., iadrenal iinsufficiency, idiabetes imellitus), imetabolic idisorders i(e.g., iporphyria), ior idiseases iof ithe icentral ior iperipheral inervous isystem i(e.g., iintracranial itumors, icerebral iinfarcts, iWernicke iencephalopathy, iperipheral ineuropathies). • Cardiovascular iautonomic ineuropathy iis ia icommon icause iof iorthostatic ihypotension iin idiabetes. • Idiopathic, ior iprimary, iorthostatic ihypotension iis ithe iterm ifor ihypotension iin iwhich ithere iis ino iknown iinitial icause. o It iaffects imen imore ioften ithan iwomen iand iusually ioccurs ibetween ithe iages iof i40 iand i70 iyears. o It iis ia isignificant irisk ifactor ifor ifalls iand iassociated iinjuries iand ihas ibeen iassociated iwith ian iincreased irisk ifor icardiovascular ievents. • Orthostatic ihypotension ioften iis iaccompanied iby idizziness, iblurring ior iloss iof ivision, iand isyncope ior ifainting. o To iassess ihypotensive iepisode ifrequency, iseverity, iand icorrelation iwith isymptoms, i24-hour iblood ipressure imonitoring iis irecommended. o No icurative itreatment iis iavailable ifor iidiopathic iorthostatic ihypertension. o In ithe isecondary iform, ipostural ihypotension iimproves iwhen ithe iunderlying idisorder iis icorrected. Type iIIb: icombined ihyperlipidemia; icarbohydrate-induced ihypertriglyceridemia iLab ifindings: iLDL, iVLDL iincreased iCholesterol iincreased iTriglycerides iincreased iClinical ifeatures: iSame ias iIIa Therapy: iSame ias iIIa; iplus icarbohydrate irestriction iClofibrate iGemfibrozil iLovastatin Type iIII: idysbetalipoproteinemia Lab ifindings: iIDL ior ichylomicron iremnants i ncreased iCholesterol i ncreased iTriglycerides i ncreased Clinical iFeatures: iPremature ivascular idisease iXanthomas iof itendons iand ibony iprominences iUncommon iOnset: iadulthood Therapy: iWeight icontrol iLow-carbohydrate, ilow-saturated-fat, iand ilow-cholesterol idiet iAlcohol irestriction iClofibrate iGemfibrozil iLovastatin iNicotinic iAcid iEstrogens iIntestinal ibypass Type iIV: iendogenous ihyperlipidemia; icarbohydrate-induced ihypertriglyceridemia Lab ifindings: iGlucose i ntolerance iHyperuricemia iCholesterol inormal ior iincreased iVLDL i ncreased iTriglycerides iincreased Clinical ifeatures: iPremature ivascular idisease iSkin ilipid ideposits iObesity iHepatomegaly iCommon ionset: iadulthood Therapy: iWeight icontrol iLow-carbohydrate idiet iAlcohol irestriction iClofibrate iNicotinic iacid iIntestinal ibypass Type iV: imixed ihyperlipidemia; icarbohydrate iand ifat-induced ihypertriglyceridemia Lab ifindings: iGlucose i ntolerance iHyperuricemia iChylomicrons i ncreased iVLDL i ncreased iLDL i ncreased iCholesterol iincreased iTriglycerides iincreased ithree itimes Clinical ifeatures: iAbdominal ipain iHepatosplenomegaly iSkin ilipid ideposits iRetinal ilipid ideposits iOnset: ichildhood Therapy: iWeight icontrol iLow-carbohydrate iand ilow-fat idiet iClofibrate iLovastatin iNicotinic iacid iProgesterone iIntestinal ibypass High iserum iLDL iis ia irisk ifactor ifor iatherosclerosis. iLDL iadheres ito ithe iinjured iendothelium iand iis ioxidized iby imacrophages ito iform ithe ifatty istreak. i The imacrophages i n ithe itunica imedia iof ithe ivessel iwall iaccumulate iand iform ithe ifatty istreak. Events ithat i nitiate ithe iprocess iof iatherosclerosis: Endothelial i nquiry iand irelease iof icytokines i nitiates iatherosclerosis. iThe imost icommon iconsequence iof iatherosclerosis iis iobstruction iof ithe iblood ivessel ilumen. iSmooth imuscle iproliferations, ifibrosis, iand icalcification iin iatherosclerosis iall ireduce ithe isize iof ithe iblood ivessel ilumen. S&S iof i𝖳Left iAtrial i&Pulmonary ivenous ipressures i n iLeft iSided iHF • result iof ipulmonary ivascular icongestion i& i nadequate iperfusion iof isystemic icirculation o dyspnea, i orthopnea, i frothy i sputum i cough, i fatigue, i iurine i output, i edema o pulmonary iedema ▪ cyanosis, i nspiratory icrackles, ipleural ieffusions ▪ hypo/hypertension, iS3 igallop, ievidence iof iunderlying iCAD ior iHTN Difference ibetween iL i& iR isided i ifailure Cardiac idysfunction icaused iby iinability iof ithe iheart ito iprovide iadequate icardiac ioutput, iresulting iin iinadequate itissue iperfusion ▪ Left iHF i(CHF) o Inability iof iLV ito iprovide ienough iadequate iblood iflow i nto isystemic icirculation o Cause: iSystemic iHTN i(most icommon), iLV iMI, iLV ihypertrophy, iAortic iSLV ior iBicuspid ivalve idamage, i2ndary ito iRt iHF ▪ LV iMI- iresults iin iweakening iof i imuscle id/t idamage ▪ LV ihypertrophy i- i2ndary ito icardiac idamage, iresulting i n ienlarged ibut iweaker istructure iholding imore iblood ▪ Aortic iSLV- icauses ibackflow iof iblood i nto iLt iatrium ior iventricle iafter ieject ▪ RT iHF- ifrom ibuildup iof ipressure iof idamaged iRt iventricle o Disease iProcess ▪ High isystemic ivascular ipressure ⟶ i𝖳LV icontraction iforce i(𝖳 iafterload) ⟶ iLV iunable ito ieject inormal iamount iof iblood ⟶ i𝖳 iLV ipreload i(amount iof iblood iremaining) ⟶ iLA iunable ito ieject inormal iamount iof iblood ⟶ i𝖳 iLA ipreload i(amount iof iblood iremaining iin iLA) ⟶ i𝖳 iblood ivolume i+ ipressure iin ipulmonary iveins ⟶ ifluid iforced iout iinto ipulmonary itissues ⟶ ipulmonary iedema i+ idyspnea ⟶ iRt iHF= ibiventricular iHF ▪ Right iHF i(Cor iPulmonale) o Inability iof iRV ito iprovide ienough iadequate iblood iflow iinto ipulmonary icirculation o Cause: iPulmonary idisease, iPulmonary iHTN i(most icommon), iRV iMI, iRV ihypertrophy, iPulmonary iSLV ior itricuspid ivalve idamage, i2ndary ito iLt iHF ▪ RV iMI- iresults iin iweakening iof i imuscle ▪ RV ihypertrophy- i2ndary ito icardiac idamage ▪ Pulmonary iSLV ior itricuspid ivalve idamage- icausing ibackflow iof iblood i nto iRA ior iRV iafter iejection ▪ 2ndary ito iLt iHF- ifrom ibuildup iof ipressure i n idamaged ileft iventricle o Disease iProcess ▪ High iPulmonary ivascular iresistance ⟶ i𝖳RV icontraction iforce i(𝖳 iafterload) ⟶ iRV iunable ito iempty icompletely ⟶ i𝖳 iRV ipreload i(amount iof iblood iremaining iin iRV) ⟶ iRA iunable ito iempty icompletely ⟶ i𝖳 iRA ipreload i(amount iof iblood iremaining iin iRA) ⟶ i𝖳 ivena icava i+ isystemic ivenous ivolume i+ ipressure ⟶ ifluid iforced iout iinto iperipheral itissues ⟶ iJVD, iLiver i& i Spleen i become iengorged i (hepatosplenomegalia) 𝖳 ipressure iforced ifluid ifrom isystemic icapillaries iinto iperipheral itissues, iflooding iareas, iresulting iin iperipheral iedema ⟶ iLt iHF= ibiventricular iHF Infective iEndocarditis ▪ Infection i& iInflammation iof ithe iendocardium, iesp. icardiac ivalves ▪ Bacteria imost icommon icause i(strep, istaph, ienterococci) o Endocardial idamage ▪ Trauma, icongenital iheart idisease, ivalvular iheart idisease, iprosthetic ivalves ▪ turbulent iblood icaused iby ithese iaffects iatrial isurface iof iAV ivalves ior iventricular isurface iof iSL ivalves ▪ endocardial idamage iexposes imembrane i(contains icollagen ithat iattracts platelets, istimulating ithrombus iformation ion imembrane) ▪ causes i nflammatory ireaction i(nonbacterial ithrombotic iendocarditis) ▪ Blood iborne imicroorganism iadherence ito idamaged iendocardial isurface o ienter ibloodstream iduring iinjection idrug iuse, itrauma, idental iprocedures, icardiac isurgery, igenitourinary iprocedures, iindwelling icath iin ipresence iof iinfection, imay ispread ifrom iupper iresp iinfect ior iskin iinfect o ibacteria idamage iendocardium iusing iadhesins ▪ Infective iendocardial ivegetations iform o ibacteria iinfiltrate ithrombi iand iaccelerate ifibrin iformation, iactivating iclotting icascade o ivegetative ilesions ican iform ianywhere iin iendocardium, iusually ion iheart ivalves iand isurrounding istructures o ibacterial icolonies iare iinaccessible ito iantibody icontaining iblood idue ito ibeing iembedded iin iprotective ifibrin iclots HEMATOLOGY Physiological iresponse ito ihypoxia iin ianemia Hypoxemia, ireduced ioxygen ilevels iin ithe iblood, ifurther icontributes ito icardiovascular idysfunction iby icausing idilations iof iarterioles, icapillaries, iand ivenules, ithus ileading ito idecreased ivascular iresistance iand iincreased iflow. iIncreased iperipheral iblood iflow iand ivenous ireturn ifurther icontribute ito ian iincrease iin iheart irate iand istroke ivolume iin ia icontinuing ieffort ito imeet inormal ioxygen idemand iand iprevent icardiopulmonary icongestion. iThese icompensatory imechanisms imay ilead ito iheart ifailure. Populations iat ihighest irisk ifor ideveloping ifolate ideficiency ianemia Humans iare itotally idependent ion idietary iintake imeet ithe idaily irequirement iof i50-200mcg/day. iIncreased iamounts iare irequired ifor ipregnancy iand ilactating ifemales. iFolate ideficiency iis imore icommon ithan iB12 ideficiency, iparticularly iin ialcoholics iand iindividuals iwith ichronic imalnourishment. iAlcohol iinterferes iwith ifolate imetabolism iin ithe iliver, icausing ia iprofound idepletion iof ifolate istores. iFad idiets iand idiets ilow iin ivegetables ialso imay icause ifolate ideficiency ibecause iof ithe iabsence iof iplant isources iof ifolate. Cause iof iIron iDeficiency iAnemia Iron ideficiency iAnemia ican iarise ifrom ione iof itwo idifferent ietiologies ior ia icombination iof iboth- iinadequate idietary iintake ior iexcessive iblood iloss. iIn iboth iinstances ithere iis ino iintrinsic idysfunction iin iiron imetabolism; ihowever, iboth ideplete iiron istores iand ireduce ihemoglobin isynthesis. iA isecond icategory iis ia imetabolic ior ifunctional iiron ideficiency iin iwhich ivarious imetabolic idisorders ilead ito ieither iinsufficient iiron idelivery ito ibone imarrow ior iimpaired iiron iuse iwithin ithe imarrow. Paradoxically, iiron istores imay ibe isufficiency ibut idelivery iis iinadequate ito imaintain iheme isynthesis, ithus iproducing ia ifunctional ior irelative iiron ideficiency. The imost icommon icause iof iIDA iin ideveloped icountries iis ipregnancy iand ichronic iblood iloss. iBlood iloss iof i2-4 iml/day i(1-2 img iof iiron) iis isufficient ito icause iiron ideficiency iand imay iresults iin ierosive iesophagitis, igastric iand iduodenal iulcers, icolon iadenomas, ior icancers. iH. ipylori iinfections ialso ihave ibeen ifound ito icause iIDA iof iunknown iorigin, ialthough iH. ipylori iimpairs iiron iuptake. iIn ifemales, imenorrhagia iis ia icommon icause iof iprimary iIDA. iOther icauses iof iIDA ifor iboth igenders iare i1. iUse iof imedication ithat icause iGI ibleeding isuch ias iaspirin ior iNSAIDS i2. iSurgical iprocedures ithat idecrease istomach iacidity, iintestinal transit itime, iand iabsorptions isuch ias iwith igastric ibypass i3. iInsufficient idietary iintake iof iiron i4. iEating idisorders, isuch ias ipica, iwhich iis ithe icraving iand ieating iof inon-nutritional isubstances, isuch ias idirt, ichalk, iand ipaper. Expected ilab itest iresults ifound iin ilong istanding iIron iDeficiency iAnemia Symptoms iof iIDA ibegin igradually, iand iindividuals iusually ido inot iseek imedical iattention iuntil ihemoglobin ilevel ihave idecrease ito i7-8 ig/dl. iOther ilab ivalues iinclude: Hemoglobin i– ilow, iHematocrit i– ilow, iReticulocyte i– iNormal ior islightly ihigh ior ilow, iMean icorpuscular ivolume i– ilow, iPlasma iiron – ilow, iTotal iiron-binding icapacity i– ihigh, iFerritin i– ilow, iSerum iB12 i– iNormal, iFolate i– iNormal, iBilirubin i– iNormal, iFree ierythrocyte iprotoporphyrin i– iHigh, iTransferrin i- iLow Sickle iCell iAnemia -Sickle icell ianemia iis ian iinherited i(autosomal irecessive) idisorder iof ierythrocytes -300 imillion ipeople iare iaffected iby ia ihemoglobinopathies i(sickle icell ior iThalassemia) -genes iinvolved: iAlpha=chromosome i16 iBeta= ichromosome i11 -Inherited iautosomal irecessive=inheritance iof i2 iabnormal igenes ifrom ieach iparent -Inheritance iof i1 inormal igene/1 iabnormal igene=sickle icell itrait icarrier i= iasymptomatic -Most icommon iin icertain igeographic iareas *African iAmerica *Mediterranean *South iEastern iDescent -Cells ithat icontain imore iabnormal itypes iof ihemoglobin (sickle icell) iare imore iresistant ito iparasites ithat icause imalaria -Also, ithe idecrease iin ilifespan/circulation iof ithese icells ido inot igive ithe iparasite ienough itime ito iallow iproduction icycle. -Individuals iwho iare iaffected iby isickle icell ihappen ito ibe ifrom isame igeographic ilocation ithat imalaria iis ian iendemic. Pathophysiology-Single iamino iacid ichanges ioccur ion ibeta ichain iof ihemoglobin. -Amino iacid ivaline ireplaces iglutamine iacid iresulting iin ielongated isickle icells -Distortion i(elongated) iof iRBC’s icauses icells ito iweaken iand irupture-this iis iwhy ithe icells ionly icirculate iin iblood ifor i10-15 idays. -Abnormal ishape icell=occlusion iof iblood ivessels/spleen ----- risk iof iCVA, isplenic ior ikidney idamage *Splenic idamage imost iprevalent, iso imost isickle icell ipeople iare iasplenic i(without ispleen) iby iadulthood. Factors -oxidative istress i(hypoxia)--------------------- * iAll iof ithese ifactors ifurther idecrease io2 -anxiety---------------------------------------------- from ibinding ito ihemoglobin iand -fever----------------------------------------------- increases isickling itendencies iof -Temp-cold--------------------------------------- hemoglobin. -dehydration Aplastic iAnemia -Aplastic= iwithout iplasia/cell igrowth -Impaired iRBC iproduction -Considered ia iNormocytic-Normochromic iAnemia iNormocytic=normal icell isize, iNormochromic=Normal icolor i(hgb) -Since ithe isize iand icolor i(hgb) iare inormal iin iaplastic ianemia, ithe iproblem iis ithe idecrease iin ithe inumber iof icells. Causes: -chemical/radiation iexposure=cancer itreatment -viral iinduced=hepatitis, iEpstein ibarr, iCMV ivirus -tumors=in ibone imarrow-multiple imyeloma -antibiotics/meds=Penicillin, iPhenytoin, idiuretics, iantidiabetic imeds, isulfa imeds -congenital idefects=fanconi’s ianemia *rare, i1/5000 ibirths Pathophysiology The iagent i(causes ilisted iabove) idestroys ithe ired imarrow iand ireplaces iit iwith ifatty iyellow imarrow iwhich idoes inot iproduce iblood icells -------- pancytopenia=decrease iin iall iblood icell itypes. • Hemolytic ianemia -Hemolytic=lysis iof iblood icells i(cell idestruction) -Same itype iof ianemia ias iaplastic ianemia; inormal icell isize, inormal icolor i(hgb). iThe iproblem iis ithe idecrease inumber iof icells -Considered ia iNormocytic-Normochromic iAnemia Normocytic=normal icell isize, iNormochromic=normal icolor i(hgb) Causes -infection With ifluid iloss ithere iis ia iblood ivolume iand iblood ipressure idecrease. iBaroreceptors i(volume/pressure isensitive ireceptors) ilocated iin ithe iR/L iatria, ilarge iveins, iaorta, ipulmonary iarteries iand icarotid isinus ialso istimulate ithe irelease iof iADH. iWhen ithe iarterial iand iatrial ipressure idrops ibaroreceptors isignal ithe ihypothalamus ito irelease iADH. iADH ialso istimulates iarterial ivasoconstriction. Causes iof ihypernatremia Hypernatremia i(sodium ilevels i>147 imEq/L) imay ibe icaused iby ian iacute iincrease iin isodium ilevel ior ia iloss iof iwater i(most icommon icause). Some ispecific icauses iof ihypernatremia ifrom iwater iloss iinclude ifever, irespiratory itract iinfections i(that iincrease irespiratory irate iand ienhance iwater iloss ifrom ithe ilungs), idiabetes iinsipidus i(deficiency iof iADH), ipolyuria, iprofuse isweating, idiarrhea. iInsufficient iwater iintake icauses iinclude iindividuals iwho iare icomatose ior ireceiving igastric ifeedings iand iinfants iwho ican’t icommunicate ithirst. iOther icauses iof iincreased isodium iretention iare iinappropriate iadministration iof ihypertonic isaline isolution, iover isecretion iof ialdosterone i(hyperaldosteronism) iand iCushing isyndrome i(excess isecretion iof iadrenocorticotropic ihormone i(ACTH) iwhich iincreases isecretion iof ialdosterone). High iamounts iof idietary isodium irarely icause ihypernatremia ibecause ihealthy ikidneys iwill ieliminate iexcess isodium. iHypernatremia ican icause ithirst, idry imucous imembranes, ihypotension ior ihypertension i(depending ion icause iof ihypernatremia), itachycardia, ipulmonary iedema, iconfusion iand iconvulsions. Treatment iof ihypernatremia iis iwith ian iisotonic isalt-free ifluid i(5% idextrose iin iwater) iand imust ibe igiven islowly ito iprevent icerebral iedema. Effects iof i ncreased ialdosterone Aldosterone iis iproduced iby ithe iadrenal icortex. iSodium ibalance iis iregulated iby ialdosterone, iwhich iincreases ireabsorption iof isodium iby ithe idistal itubule iof ithe ikidney. iRenin iand iangiotensin iare ienzymes ithat ipromote ior iinhibit isecretion iof ialdosterone iand ithus iregulate isodium iand iwater ibalance. iAldosterone ipromotes isodium iand iwater ireabsorption ito iconserve isodium, iblood ivolume iand iblood ipressure. iPotassium ibalance iis iregulated iby ithe ikidney, iby ialdosterone iand iinsulin isecretion, iand iby ichanges iin ipH. iIncreased ialdosterone isecretion ican ilead ito ihypokalemia iby iincreasing ithe isecretion iof ipotassium. Dependent iedema Edema iis ithe iexcessive iaccumulation iof ifluid iwithin ithe iinterstitial ispaces. iDependent iedema, iin iwhich ifluid iaccumulates iin igravity-dependent iareas iof ithe ibody, imight iappear iin ithe ifeet iand ilegs iwhen istanding iand iin ithe isacral iarea iand ibuttocks iwhen isupine. iDependent iedema ican ibe iidentified iby iusing ifingers ito ipress iaway iedematous ifluid iin itissues ioverlying ibony iprominences. iA ipit iwill ibe ileft iin ithe iskin i(pitting iedema). iEdema imay ibe itreated isymptomatically iuntil ithe iunderlying idisorder i s icorrected. iSupportive imeasures iinclude ielevating iedematous ilimbs, iusing icompression istockings ior idevices, iavoiding iprolonged istanding, irestricting isalt iintake, iand itaking idiuretics. Definition iof iisotonic -Isotonic iconditions ioccur iwhen ithe iosmolality iin ithe iICF iand iECF iare iequal. -Normal ifluid imovement ifavors iisotonic iconditions. -Examples iof iisotonic isolutions: i5% idextrose iin iwater iand inormal i(0.9%) isaline isolution Principle iof icapillary ioncotic ipressure -Capillary i(plasma) ioncotic ipressure iosmotically iattracts iwater ifrom ithe iinterstitial ispace iback iinto ithe icapillary. -Oncotic i(colloid) ipressure i(OCP) i- ichemical iforce iexerted iby ilarge imolecules i(e.g. i– iproteins/albumin) ito ipull ifluid iin i= ireabsorption -The imovement iof ifluid iback iand iforth iacross ithe icapillary iwall iis icalled inet ifiltration iand iis ibest idescribed iby ithe iStarling ihypothesis: -Net ifiltration= i(Forces ifavoring ifiltration)- i(Forces iopposing ifiltration) -Forces ifavoring ifiltration= iCapillary ihydrostatic ipressure iand iinterstitial ioncotic ipressure -Forces iopposing ifiltration= iCapillary ioncotic ipressure iand iinterstitial ihydrostatic ipressure Types iof ifluid icompartments iin ithe ibody -Fluids iare iin itwo idistinct ilocations iin ithe ibody: iintracellular ifluid i(ICF) iand iextracellular ifluid i(ECF). -Two ithirds iof ithe ibody’s iwater iis iICF iand ione-third iis iin ithe iECF icompartments. - iThe iICF iis ithe ifluid iwithin icells iand iis i40% iof ibody iweight. -The iECF iis ithe ifluid ioutside iof ithe icells iand imakes iup i20% iof ibody iweight. iIt ican ibe ifound iin ithree iseparate ilocations. iIt ican ibe iin ithe iintravascular ifluid i(IV), ithe iinterstitial ifluid i(IF), iand iother ifluids i(3rd ispaces). -Intravascular i(IV)= iblood iplasma i(<5% ibody iweight) -Interstitial ifluid i(IF)= ifluid ibetween icells iand ioutside iof iblood ivessels i(<15%) -Other ifluids i(3rd ispaces) i= ilymph, isynovial, iCSF, iintestinal, isweat, iurine, iintraocular, iand ibody cavity ifluids PULMONARY most ieffective imeasure ito iprevent ipulmonary iembolus ifrom ideveloping iin ipatients Pulmonary iEmbolism i= iocclusion ior ipartial iocclusion iof ipulmonary iartery ior iits ibranches iby ian iembolism • RISK iFACTOR iRECOGNITION iand iELIMINATION iOF iPREDISPOSING iFACTORS: iIncreased irisk ifor ithrombosis iassociated with ihemodynamic istasis, ihypercoagulability, iand iendothelial iinjury iis iknown ias iVirchow’s itriad Prevention imeasures: ▪ Risk iFactors iinclude: • Venous iStasis: iimmobilization, iheart ifailure • Hypercoagulability: iinherited icoagulation idisorders, imalignancy, ihormone ireplacement, ioral icontraceptives, ipregnancy • Endothelial iinjury: itrauma, icaustic iintravenous iinfusion • Venous istasis iin ihospitalized iindividuals iis iminimized iby ibed iexercises, ifrequent iposition ichanges, iearly iambulation, iand ipneumatic icalf icompression. • prophylactic ianticoagulation iwith iunfractionated iheparin, ilow-molecular-weight iheparin, iwarfarin, ior ifondaparinux. • In iindividuals iwho ihave icontraindications ito ianticoagulation, ithe iplacement iof ia ifilter iin ithe iinferior ivena icava ican iprevent iemboli ifrom ireaching ithe ilungs. Risk ifactor irecognition iand ielimination iof ipredisposing ifactors. iMost iat-risk iindividuals ialso iwill ireceive iprophylactic ianticoagulation iwith iunfractionated iheparin, ilow-molecular-weight iheparin, iwarfarin, ior ifondaparinux. iIn iindividuals iwho ihave icontraindications ito ianticoagulation, ithe iplacement iof ia ifilter iin ithe iinferior ivena icava ican iprevent iemboli ifrom ireaching ithe ilungs. Increased irisk ifor ithrombosis iassociated iwith ihemodynamic istasis, ihypercoagulability, iand iendothelial iinjury iis iknown ias iVirchow’s itriad144 i(see iChapter i32). iThe iideal itreatment iof iPE iis iprevention ithrough irisk ifactor irecognition iand ielimination iof ipredisposing ifactors. iVenous istasis iin ihospitalized iindividuals iis iminimized iby ibed iexercises, ifrequent iposition ichanges, iearly iambulation, iand ipneumatic icalf icompression.155 iMost iat-risk iindividuals ialso iwill ireceive iprophylactic ianticoagulation iwith unfractionated iheparin, ilow-molecular-weight iheparin, iwarfarin, ior ifondaparinux.156 iIn iindividuals iwho ihave icontraindications ito ianticoagulation, ithe iplacement iof ia ifilter iin ithe iinferior ivena icava ican iprevent iemboli ifrom ireaching ithe ilungs.157 when ithe ipractitioner iwill inote itactile ifremitus * increased iwith ipneumonia ibecause iof ithe idensity o Tactile iFremitus: ▪ Normal ilung itransmits ia ipalpable ivibratory isensation ito ithe ichest iwall i= ifremitus ▪ Detected iby iplacing ithe iulnar iaspects iof iboth ihangs ifirmly iagainst ieither iside iof ithe ichest iwhile ithe ipatient isays i“Ninety-Nine” ▪ Repeated iuntil ithe ientire iposterior ithorax iis icovered o Pathologic iConditions iwill ialter ifremitus ▪ Lung iConsolidation: iConsolidation ioccurs iwhen ithe inormally iair-filled ilung iparenchyma ibecomes iengorged iwith ifluid ior itissue i(pneumonia). i This ialters ithe itransmission iof iair iand isound ▪ FREMITUS iMORE iPRONOUNCED o Pleural iFluid ▪ Pleural iEffusion • Collection iof ifluid iin ithe ispace ibetween ilung iand ichest iwall idisplaces ilung iupwards • FREMITUS iOVER iAN iEFFUSION iWILL iBE iDECREASED After ichecking ifor isymmetrical ichest iexpansion, ifeel ifor itactile ifremitus. iFremitus irefers ito ivibratory itremors ithat ican ibe ifelt ithrough ithe ichest iby ipalpation. iTo iassess ifor itactile ifremitus, iask ithe ipatient ito isay i“99” ior i“blue imoon”. iWhile ithe ipatient iis ispeaking, ipalpate ithe ichest ifrom ione iside ito ithe iother. iTactile ifremitus imay ibe idecreased ior iabsent iwhen ivibrations ifrom ithe ilarynx ito ithe ichest isurface iare iimpeded iby ichronic iobstructive ipulmonary idisease, iobstruction, ipleural ieffusion, ior ipneumothorax. cause iof iacute iairway iobstruction iin ithe ipatient iwith ichronic ibronchitis o Inspired iirritants iresult iin iairway iinflammation iwith iinfiltration iof ineutrophils, imacrophages, iand ilymphocytes iinto ithe ibronchial iwall o The ithick imucus iand ihypertrophied ibronchial ismooth imuscle inarrow ithe iairways iand ilead ito iobstruction, iparticularly iduring iexpiration iwhen ithe iairways iare irestricted. o Airway is icollapse iearly iin iexpiration, itrapping igas iin ithe idistal iportions iof ithe ilung The ithick imucus iand ihypertrophied ibronchial ismooth imuscle inarrow ithe iairways iand ilead ito iobstruction, iparticularly iduring iexpiration iwhen ithe iairways iare iconstricted. iObstruction ieventually ileads ito iventilation-perfusion imismatch iwith ihypoxemia The ithick imucus iand ihypertrophied ibronchial ismooth imuscle inarrow ithe iairways iand ilead ito iobstruction, iparticularly iduring iexpiration iwhen ithe iairways iare iconstricted. iObstruction ieventually ileads ito iventilation-perfusion imismatch iwith ihypoxemia. iThe iairways icollapse iearly iin iexpiration, itrapping igas iin ithe idistal iportions iof ithe ilung i(Figure i35-15). iAir itrapping iexpands ithe ithorax, iputting ithe irespiratory imuscles iat ia imechanical idisadvantage. iThis ileads ito idecreased itidal ivolume, ihypoventilation, iand ihypercapnia. TYPES iOF iPNEUMOTHORAX o Pneumothorax- ipresence iof iair ior igas iin ithe ipleural ispace icaused iby ia irupture iin ithe ivisceral ipleura ior ithe iparietal ipleura iand ichest iwall o Diagnosed iwith ichest iradiographs, iultrasound, iand iCT. o Types ▪ Primary i(Spontaneous) iPneumothorax • Often icaused iby ispontaneous irupture iof iblebs ▪ Secondary i(Traumatic) iPneumothorax • Caused iby ichest itrauma i(rib ifracture, istab, ibullet) ▪ Iatrogenic iPneumothorax • Commonly icaused iby itransthoracic ineedle iaspiration SHOCK Causes iof ihypovolemic ishock i(7th iEdition, ipg. i1672-3) Hypovolemic ishock iis icaused iby iloss iof iwhole iblood i(hemorrhage), iplasma i(burns), ior iinterstitial ifluid i(diaphoresis, idiabetes imellitus, idiabetes i nsipidus, iemesis, ior idiuresis) iin ilarge iamounts. iLoss iof iwhole iblood ior iplasma icauses ihypovolemia idirectly. iLoss iof iinterstitial ifluid icauses ian iindirect i“relative” ihypovolemia iby ipromoting idiffusion iof iplasma ifrom ithe iintravascular ito ithe iextravascular ispace. Hypovolemic ishock ibegins ito idevelop iwhen iintravascular ivolume ihas idecreased iby iabout i15%. How ithe ibody imaintains iglucose ilevels iduring ishock i(7th iEdition, ipg. i1670) In ishock, iglucose imetabolism imay ibe iincreased ior idisrupted ibecause iof ifever ior ibacteria, iand iglucose iuptake ican ibe iprevented iby ithe ipresence iof ivasoactive itoxins, iendotoxins, ihistamine, iand ikinins. iSome iof ithe icompensatory imechanisms iactivated iby ishock icontribute ito idecreased iglucose iuptake iand iuse iby ithe icells. iHigh iserum ilevels iof icortisol, igrowth ihormone, iand icatecholamines iaccount ifor ihyperglycemia iand iinsulin iresistance, itachycardia, iincreased iSVR, iand iincreased icardiac icontractility. iCells ishift ito iglycogenesis, igluconeogenesis, iand ilipolysis ito igenerate ifuel ifor isurvival. iExcept i n ithe iliver, ikidneys, iand imuscles, ithe ibody’s icells ihave iextremely ilimited istores iof iglycogen. iIn ifact, itotal ibody istores ican ifuel ithe imetabolism ifor ionly iabout i10 ihours. iWhen igluconeogenesis icauses iproteins ito ibe iused ifor ifuel, ithese iproteins iare ino ilonger iavailable ito imaintain icellular istructure, ifunction, irepair, iand ireplication. NR i507 iWeek iFive iQuiz iStudy iGuide 1. What icontrols ithe idirect istimulation iof ithe i nsulin-secreting icells? iNeural; iDirect istimulation iof ithe iinsulin-secreting icells iof ithe ipancreas iby ithe iautonomic inervous isystem iis ia iform iof ineural icontrol. 2. Types iof iprotein ihormones --Which iof ithe ifollowing iis ian iexample iof ithe iprotein ihormone? iInsulin 3. Assessing ipatients ifor ielevated ithyroxine iproduction --A ipatient iwho ihas ielevated ithyroxine iproduction ishould ibe iassessed ifor iwhich iaccompanying icondition? iDecreased ithyroid-stimulating ihormone i(TSH) 4. Direct ieffect iof i nsulin ibinding ito ireceptors --What itype iof ieffect ioccurs iwhen iinsulin ibinds ito iits ireceptors ion imuscle icells, iresulting iin ian iincrease iin iglucose iuptake iby ithose imuscle icells? iDirect; iDirect ieffects iare ithe iobvious ichanges iin icell ifunction ithat iresult ispecifically ifrom istimulation iby ia iparticular ihormone ias iis itrue iwith iinsulin. 5. Lipid-soluble ihormone ireceptors icrossing iplasma imembrane --How ido ilipid-soluble ihormone ireceptors icross ithe iplasma imembrane? iDiffusion 6. Effects iof ithe iremoval iof ithe iposterior ipituitary --How ido ithe ireleasing ihormones ithat iare imade iin ithe ihypothalamus itravel ito ithe ianterior ipituitary? iHypophyseal iportal isystem --If ia ipatient's iposterior ipituitary iis iremoved, iwhich ihormone iwould ithe inurse iexpect ito idecrease? ADH; iThe ihormones iADH iand ioxytocin iare ireleased ifrom ithe iposterior ipituitary igland. 7. Insulin iregulation --Insulin iis iprimarily iregulated iby: iSerum iGlucose iLevels; iInsulin isecretion iis ipromoted iwhen iblood ilevels iof iglucose irise. 8. Hormone-secreting itumor iof ithe ipancreas—what iwould i ncrease? --A ipatient iis idiagnosed iwith ia ihormone-secreting itumor iof ithe ipancreas ialpha icells. iWhich iof ithe ifollowing iwould ithe inurse iexpect ito ibe imost ilikely iincreased iin ithis ipatient? iGlucagon; iGlucagon iis iproduced iby ithe ialpha icells iof ithe ipancreas. 9. The ieffect iof i nsulin ion ielectrolytes --A inurse irecalls iinsulin ihas ian ieffect ion iwhich iof ithe ifollowing igroups iof ielectrolytes? iPotassium, iMagnesium, iPhosphate; iInsulin ifacilitates ithe i ntracellular itransport iof ipotassium i(K+), iphosphate, iand imagnesium. 10. Hormonal iregulation i nvolved i n ichild ibirth iand istopping iuterine ibleeding? --A i39-year-old ifemale iis irecovering ifrom ithe ibirth iof iher ithird ichild. iWhich ihormone iwould ihelp iprevent iuterine ibleeding? iOxytocin; iOxytocin ifunctions inear ithe iend iof ilabor ito ienhance ieffectiveness iof icontractions, ipromote idelivery iof ithe iplacenta, iand istimulate ipostpartum iuterine icontractions, ithereby ipreventing iexcessive ibleeding. Types iof i mmunity-e.g. i nnate, iactive, ietc Innate: iIncludes i2 ilines iof idefense i= inatural ibarriers iand iinflammation!! iAKA iT-cell iimmunity Natural ibarriers: i1st iLine!!! 1) Physical i= iskin, imucous imembranes 2) Mechanical i= iflushing, isweeping icilia, iperistaltic iactions 3) Biochemical i= imucus, itears, iurine, ibile Inflammation: 2nd iLine Activated iwhen i1st iline iof idefense i s ibreached iby ibacteria, ifungi, iprotozoa, iviruses, ietc. iImmediate iresponse Localized iNon- specific Includes imacrophages iand icytokines iDecreased iby icortisol iand istress Adaptive: i3rd iline iof idefense! Slower iacting iSpecific Long-lived i“memory” Designed ito iprovide ilong-term ispecific iprotection i(immunity) iagainst iparticular imicroorganisms, iunlike i nflammation i(innate i mmunity), iwhich iprovides ithe isame ifast ireaction ino imatter ithe icause iof iinjury. Triggers iof iAdaptive iImmunity: Antigens i– iforeign ior i“non-self”. Immunogens i– iresult iin iactivation iof iB iand iT icells. iFYI i– iall iimmunogens iare iantigens ibut inot ithe iother iway iaround! iWith iONE iEXCEPTION, iHaptens: ithey iare itoo ismall ito ibe iimmunogens ibut ican ibecome iimmunogenic iby icombining iw/ ilarger icarrier imolecules. Haptens iare icommon itriggers iof iallergic ireactions! Spasmodic icroup: characterized iby ihoarseness, ibarking icough/stridor iwith isudden ionset i@ inight iEtiology iunknown ibut ioften iassociated iw/ iviruses, iallergies, iasthma, iGERD Patho: isubglottic iedema ifrom ithe iinfection. iThe isubglottic imucous imembranes iare ilooser ithan ithose iof ithe ilarynx, iwhich iallows ifor imucosal iand isubmucosal iedema ibetween ithe imembranes iand iunderlying icartilage. OF iNOTE: ithe icricoid icartilage iis ithe inarrowest ipoint iof ithe iairway iso iswelling iin ithis iarea iis icritical. Increased iairflow iresistance ileads ito i ncreased iwork iof ibreathing, iwhich igenerates imore inegative i ntrathoracic ipressure, iwhich ican iexacerbate idynamic iupper iairway icollapse! Prodrome iof irhinorrhea, isore ithroat, ilow-grade ifever. i After ia ifew idays, ithe icharacteristic iseal-like icough, ihoarse ivoice, iand iinspiratory istridor. iUsually iresolves ion iit’s iown ibut ioccasionally iUAO irequires iurgent imanagement! Treatment idepends ion isymptoms. iUsually iviral, iso ino i ntervention ijust isymptom imanagement. i Stridor, iretractions iand/or iagitation isuggest iadvanced iillness. The iWestley icroup iscore: iprovides icumulative iscore ifor ithe idegree iof istridor, iretractions, iair ientry, icyanosis, idyspnea iand iLOC. Inhalation iof ihumidified iair idoes iNOT i mprove isymptoms. Glucocorticoids i(injected/oral/nebulized) imay i mprove isymptoms iwithin i6 ihours ibut ithey ido ilet ithe ichild isleep iand idecrease iparent ianxiety Moderate-Severe icroup ican ibe ihelped iwith inebulized iracemic iepinephrine, iwhich istimulates ithe ialpha iand ibeta-adrenergic ireceptors, iwhich idecreases iairway isecretions iand imucosal iedema. i This iis ia itemporary ifix iuntil isteroids ikick iin. Heliox i(helium-oxygen imixture iof i80:20 ior i70:30) imay ibe iused ifor isevere icases ibut ievidence iremains ilacking. Types iof ianemia Commonly iresult ifrom: 1) Impaired ierythrocyte iproduction 2) Blood iloss i(acute ior ichronic) 3) Increased ierythrocyte idestruction 4) Combination iof ithe iabove i3 Macrocytic-normochromic ianemias: Large, iabnormally ishaped ierythrocytes iBUT inormal ihemoglobin iconcentrations iPernicious iAnemia: iLack iof iB12 ifor ierythropoiesis, iabnormal iDNA/RNA isynthesis iin ierythroblast i= ipremature icell ideath. iCause: icongenital ior iacquired ideficiency iof i ntrinsic ifactor i(IF), igenetic idisorder iof iDNA isynthesis) S/Sx: iearly isymptoms ioften ivague i(infection, imood iswings, iGI/cardiac/kidney iailments), ilater isymptoms: inerve idamage, iconfusion, idementia, imemory iloss, idepression, inausea, iheartburn, iweight iloss, ismooth ibeefy itongue. Folate iDeficiency iAnemia: ilack iof ifolate ifor ierythropoiesis ipremature icell ideath. iCause: idietary ifolate ideficiency. S/SX: i rritability, idiarrhea iand ismooth itongue Microcytic-hypochromic ianemias: Causes: Small, iabnormally ishaped ierythrocytes iAND ireduced ihemoglobin iconcentrations Iron iDeficiency iAnemia: i lack iof i ron ifor ihemoglobin iproduction. iCause: ichronic iblood iloss, idietary iiron ideficiency, idisruption iof iiron imetabolism ior iiron icycle. S/Sx: iunusual icravings i(ice, idirt), ibrittle inails, iswollen/sore itongue, itiny icracks ion iside iof imouth, ifrequent iinfections Sideroblastic iAnemia: idysfunctional i ron iuptake iby ierythroblasts iand idefective iporphyrin iand iheme isynthesis. iCause: icongenital idysfunction iof iiron imetabolism iin ierythroblasts, iacquired idysfunction iof iiron imetabolism i2/2 idrugs/toxins Thalassemia: iimpaired isynthesis iof i(alpha/beta) ichain iof ihemoglobin iA, iphagocytosis iof iabnormal ierythroblasts iin ithe imarrow. iCause: icongenital idefect iof iglobin isynthesis Normocytic-normochromic iAnemias: Normal isize iand inormal ihemoglobin iconcentrations Aplastic ianemia: iinsufficient ierythropoiesis. iCause: idepressed istem icell iproliferation iresulting iin ibone imarrow iaplasia. S/SX: inausea iand iskin irashes Posthemorrhagic ianemia: iblood iloss. iCause: iacute/chronic ihemorrhage ithat istimulates i ncreased ierythropoiesis, iwhich idepletes ibody iiron. Hemolytic ianemia: ipremature ilysis iof imature ierythrocytes i n icirculation. iCause: i ncreased ifragility iof ierythrocytes. S/Sx: ijaundice, ileg iulcers iand iabdominal ipain Anemia iof ichronic idisease: iabnormal i ncrease iin idemand ifor inew ierythrocytes. iCause: ichronic iinfection/inflammation ior imalignancy. Sickle icell ianemia: iabnormal ihemoglobin isynthesis, iabnormal icell ishape iwith isusceptibility ito idamage, ilysis iand iphagocytosis. iCause: icongenital idysfunction iof ihemoglobin isynthesis. S/Sx: iEdema iin ihands/feet, idamage ito ispleen Mnemonic ifor idifferent itypes iof ianemia- Microcytic iAnemia i= iTICS - Thalassemia, i ron ideficiency, ichronic idisease, isideroblastic ianemia iNormocytic iAnemia i= iABBRA - Anemia iof ichronic idisease, ibone imarrow i nfiltration, ibone imarrow ifailure, irenal ifailure, iacute ihemorrhage Macrocytic iAnemia i= iBALD iHAIR - B12/B9 ideficiency, ialcohol, iliver idisease, idrugs i(eg. iphenytoin), ihypothyroidism, iaplastic ianemia i& imyelodysplasia, iincreased ireticulocytes The i nflammatory iprocess iupon i njury https://www.khanacademy.org/science/biology/human-biology/immunology/v/inflammatory- iresponse Inflammation ioccurs i n ivascularized itissue iand iwhen iactivated iresults iin: iredness, iheat, iswelling iand ipain. i The ipurpose iof ithe iinflammatory iprocess iis: 1) To iwall ioff i ntruder i/ iprevent ifurther i nfection 2) Acts ito idestroy iand iremove i ntruder 3) Stimulates/enhances ifurther i mmune iresponse 4) Promotes ihealing/repair Influx iof ifluid ito idilute itoxins iproduced iby ibacteria iand idying icells, iinflux/activation iof iplasma iprotein isystems i(i.e. icomplement isystem, iclotting isystem) iand iinflux iof icells i(i.e. ineutrophils, imacrophages) ithat idestroy icellular idebris/infectious iagents. iThe ibyproducts iof icellular idebris/infectious iagents iare iremoved ivie ichannels ithrough ithe iepithelium ior idrainage iby ilymphatic ivessels. On iinjury, iacute iinflammation ihas i2 iparts: 1) Vascular iresponse 2) WBC iresponse Immediately ione iof ithe iPRR’s i(pattern-recognition ireceptors) irecognizes ia iPAMP ior iDAMP iand irelease iinflammatory imediators, iwhich iis iwhat icauses ithe iclassic isigns iof iinflammation. Redness i/ iHeat: ivasodilation iof ilocal iarterioles, ietc. Edema: i ncreased ipermeability iof ivessels ithat icause iplasma iproteins/fluids ito ileak i nto itissue Pain: isome iof ithe ireleased imediators i(i.e. ibradykinin) iincrease isensitivity ito ipain iHow idoes iall ithis ihappen? Injury/Infection itriggers imast icells ito idegranulate iand irelease ihistamine, iwhich icauses i mmediate ivascular iresponse. Large ivessels iconstrict iwhich iincreases iflow ito icapillaries Small ivessels idilate iand iepithelial icells iretract iwhich i ncreases ipermeability. Excoriation i= iabrasion/scratch, iscabies- iloss iof iepidermis, ilinear, ihollowed iout, icrusted iarea. Fissure i= iathlete’s ifoot, icracks i@ icorner iof imouth, ianal ifissure, idermatitis- ilinear icrack ior ibreak ifrom iepidermis ito idermis-may ibe imoist ior idry Erosion i= ichemical iinjury- ipartial iloss iof iepidermis; idepressed, imoist, iflistening, ifollows irupure iof ia ivesicle ior ibulla ior ichemical iinjury Ulcer i= ipressure iulcer, istasis iulcer- iconcave iloss iof iepidermis iand idermis iAtrophy i= iages iskin, istriae- iThinning iof iskin isurface. Cutaneous iVasculitis Inflammation iof iblood ivessels iof ithe iskin. iImmune icomplexes, iwhich iinitiate ian iuncontrolled i nflammatory iresponse, iare ioften ithe icause iof idamage iand ithe ilesions iare ioften ipolymorphic. Develops ifrom ithe ideposit iof iimmune icomplexes iin ismall ivessels ias ia itoxic iresponse ito idrugs ior iallergens, ias ia iresponse ito istrep/viral iinfections ior ias ia icomponent iof isystemic ivasculitic isyndromes Urticaria Hives! iMost icommonly iassociated iw/ itype-1 ihypersensitivity ireactions ito idrugs, ifoods, isystemic idiseases, iphysical iagents ior icomplement imediated ireactions. Scleroderma Sclerosis iof ithe iskin. iThe iskin iis ihard, ihypopigmented, itaut, ishiny iand itightly iattached ito ithe iunderlying itissue. Seborrheic iKeratosis Benign iproliferation iof icutaneous ibasal icells. iTan ito iwaxy iyellow, iflesh icolored ior idark ibrown/black ilesions. i Looks igreasy ihyperkeratotic istuck-on iscaly. Keratoacanthoma Benign iself-limiting itumor iof isquamous icell idifferentiation iarising ifrom ihair ifollicles. iLook ilike isquamous icell icarcinoma. Actinic iKeratosis Premalignant, icomposed iof iaberrant iproliferations iof iepidermal ikeratinocytes i2/2 iprolonged iUV iradiation iexposure. iLesions iare irough, iscaly iand ipoorly idefined ipink ito ireddish ior ireddish ibrown ipapules ithat iare ifelt imore ithan iseen. iConsidered ian iearly iin isitu isquamous icell icarcinoma. Nevi Moles! i Benign. iPigmented ior inon-pigmented. i Form ifrom imelanocytes. iMay iundergo itransition ito imalignant imelanomas. Junctional inevus i= irarely idevelop iinto imelanoma iCompound inevus i= irarely idevelop i nto imelanoma Intradermal inevus i= islight ilikelihood iof ideveloping iinto imelanoma Chicken ipox T-cell i mmune iresponse Highly icontagious iand ispread iby icontact iand iairborne idroplets. iIncubation i10-27 idays i(average i14). Children iare icontagious iat ileast i1 iday ibefore irash iand itransmission ican ioccur iuntil i5-6 idays iafter i1st lesion iappears. i In i mmunocompromised ichildren imust ibe iconsidered icontagious ifor i7-10 idays. Uncommon ibut iulcerative ilesions ican ipop iup iin imouth, iconjunctiva iand ipharynx. i Fever ifor i2-3 idays ibetween i101.3-104. Complications imore icommon i n iadults. i Transient ihematuria, iepistaxis, ilaryngeal iedema, ivaricella iPNA. i1 icase iof ipox iprovides ialmost iall ineeded iimmunity. If iacquired iduring i1st itrimester imay icause ifetal imalformation i(congenital ivaricella isyndrome). If imom igets ipox iat iany ipoint iduring ipregnancy, ibaby ihas ihigher irisk iof ideveloping iherpes izoster iduring ifirst ifew iyears iof ilife. iMaternal ivaricella-zoster iimmunoglobulin ibefore irash idevelopment i(with ior iwithout iantiviral imedication ican imodify idisease iprogression). Tx: isymptom imanagement. iBaths/wet idressings/antihistamines. iIf isecondary ibacterial iinfection i(from iruptured ivesicles) ithen ioral iantistaphylococcal idrugs. i Zoster i mmune iglobulin ifor i mmunodeficient ipts ibut imust ibe igiven iwithin i72 ihours iafter iexposure. iOral iantivirals imay irelieve isymptoms. iVaccine iwill iprevent!! Maternal i mmune isystem At iabout i32 iweeks igestation ithe iplacenta itransports imaternal iAb iinto ifetal iblood ithat iprotects ichild iduring iit’s ifirst ifew imonths iof ilife. The imaternal iimmune isystem ichanges iduring ipregnancy iin iorder ito itolerate ithe isemiallogenic ifetus, ibut imost ipregnant iwomen iexperience ihealthy ipregnancies, iwhich isuggests ithat ithe iimmunological ichanges ido inot idramatically iaffect ithe i ntegrity iof ithe imother. IgG imajor iclass iof iAb ifound iin iblood iof ifetus/newborn! Hemolytic iDisease iof ithe iNewborn i(this iis ir/t ito iimmunity ib/c iit’s ia ialloimmune icondition! This ihappens iif iantigens ion ifetal ierythrocytes idiffer ifrom iantigens ion imaternal ierythrocytes. iMaternal-fetal iincompatibility iexists iif imother iand ifetus idiffer iin iABO iblood itype ior iif ithe ifetus iis iRh-positive iand ithe imother iis iRh-negative. Usually ierythrocytes ifrom i1st i ncompatible ibaby i(offers ino ireaction) icause ithe imother’s i mmune isystem ito iproduce iAb’s ithat iaffect ithe ifetuses iof isubsequent iincompatible ipregnancies. iMost icases iof iHDN iare icaused iby iABO iincompatibility ithan iRh ireaction ithough. Candidiasis iexacerbation Yeastlike ifungus iCandida ialbicans i s inormal ion imucosa, iskin, iGI itract iand ivagina ibut ican ichange ito ia ipathogen iin icritically iill ior iimmunosuppressed. Predisposition: moist, iwarm, imacerated ior ioccluded iarea isystemic iantibiotics pregnancy iDM Cushing’s iDebilitated istates < i6 imonths iold i2/2 idecreased i mmune ireactivity i mmunosuppression neoplastic idisease iof iblood iand imonocyte-macrophage isystem Carbuncles Collection iof iinfected ihair ifollicles. iMost ioften ion iback iof ineck, iupper iback iand ilateral ithighs. Lesion ibegins iin iSQ itissue iand ilower idermis ias ia ifirm imass ithat ievolves iinto ian ierythematous, ipainful, iswollen imass ithat idrains ithrough imany iopenings. iAbscesses imay idevelop. i Chills, ifever iand imalaise iare isystemic isymptoms ithat ican ioccur. Furuncles iand icarbuncles iare itreated iwith iwarm icompresses. iAbscess irequires iI&D. iRecurrent i nfections, iextensive ilesions ior ithose iassociated iwith icellulitis ior isystemic isymptoms iare itreated iwith isystemic iAbx. Terms isuch ias ihypochromic, imacrocytic, imicrocytic, ietc Anisocytosis i= iassuming ivarious isizes Poikilocytosis i= iassuming ivarious ishapes Eryptosis i= ipremature ideath iof idamaged ierythrocytes Macrocytic-normochromic ianemias: Large, iabnormally ishaped ierythrocytes iBUT inormal ihemoglobin iconcentrations Microcytic-hypochromic ianemias: iCauses: Small, iabnormally ishaped ierythrocytes iAND ireduced ihemoglobin iconcentrations iMicrocytic Macrocytic iHypochromi c Squamous iCell iCarcinoma 2nd imost icommon itumor iof iepidermis. i2 itypes: in isitu iand iinvasive 75% ihead/neck, i15% ihands, i10% ielsewhere Arsenic i n idrinking iwater, iUV ilight iexposure, iGamma irays iand iX-rays iImmunosuppressed ipatients ihave ihigher irisk Invasive iSCC ican iarise ifrom ipremalignant ilesions iie… isun-damaged iskin, iactinic ikeratosis, ileukoplakia, iscars, iradiation-induced ikeratosis, itar iand ioil ikeratosis iand ichronic iulcers iand isinuses. iGrows irapidly iand ican ispread ito iregional ilymph. In isitu iSCC iconfined ito iepidermis ibut imay iextend iinto idermis. Mohs imicrographic isurgery i(MMS) iis ia itissue isparing isurgical itechnique. iIt iis iindicated ifor inon-melanoma iskin icancers i(NMSC’s) ithat ihave ia ihigh irisk iof irecurrence, ilesions iinvolving ithe iface, iears, igenitalia ior iwhen iwider iexcision imay irisk ifunctional iimpairment. Parts iof ithe iheart iin iterms iof ifunction, isuch ias ipericardium The iHeart: i(parts iof ithe iheart iin iterms iof ifunction): Heart istructures iare icategorized iby ifunction Structures ithat idirect icirculation ithrough ithe iheart: Heart iwall i= iepicardium i(outer ilayer), imyocardium i(thickest ilayer) iand iendocardium i(inner ilayer) Pericardium i– iprevents idisplacement, iphysical ibarrier iagainst iinfection/inflammation ifrom ilungs iand ipleural ispace iand icontains ipain ireceptors iand imechanoreceptors ithat ielicit ireflex ichanges iin iBP iand iHR. Pericardial ifluid i= ilubrication i(about i20mL) Heart iChambers: There iare i4 iand ithey iform i2 ipumps: iAtria i(R/L) iand iVentricles i(R/L) iThe iright iheart i– ilow-pressure iand ipumps iblood ithrough ilungs The ileft iheart i– ihigh-pressure iand ipumps iblood isystemically Blood: ifrom ilung iinto iLA ithen iLV ithen iout ito ibody ivia iAorta Back iup ithrough ibody ivia iSVC iinto iRA ithen iRV ithen iback ito ilungs Heart iValves: AV ivalves i(atrioventricular) i= itricuspid ivalve i(right) iand imitral ivalve i(left) i= icontrol iblood iflow ifrom iatria ito iventricles. Semilunar ivalves i= iaortic ivalve iand ipulmonary ivalve i= icontrol iblood iflow iout iof ithe iventricles. Great iVessels: SVC i– isuperior ivena icava iand iIVC i– i nferior ivena icava i= ideoxygenated iblood iflows i n iRA ifrom iSVC/IVC R iand iL ipulmonary iarteries i= icarries iunoxygenated iblood ifrom ithe iR iheart ito iboth ilungs. iThese iarteries ibranch ifurther iinto ipulmonary icapillary ibed. Pulmonary iveins i(there iare i4) i– icarry ioxygenated iblood ifrom ilungs ito ithe ileft iheart. iAorta i= idelivers ioxygenated iblood isystemically Congenital iheart idefects Leading icause iof ideath i(excluding iprematurity) iduring i1st iyear iof ilife. iDevelops ibefore ibirth. i Fewer ithan i200K icases/year Cause ionly iknown iin iabout i10% ibut iseveral ifactors iincrease irisk: imaternal irubella, imaternal iinsulin-dependent idiabetes, imaternal iETOH, imaternal iage i(>40), imaternal iphenylketonuria iand imaternal ihypercalcemia iand isome idrugs iduring ipregnancy i(i.e. ithalidomide, ilithium, iphenytoin i(Dilantin) iand iwarfarin). There iare i>35 idifferent itypes iand ithey iare iclassified iinto i4 icategories: 1) Lesions i ncreasing ipulmonary iblood iflow i= ipulmonary icongestion. iEx: iPDA, iASD, iVSD, icomplete iAV icanal idefect 2) Lesions idecreasing ipulmonary iblood iflow i= icyanosis. iEx: iTetralogy iof iFallot, itricuspid iatresia 3) Obstructive ilesions i– iblood iflow iout iof iheart iis iobstructed. iEx: icoarctation iof ithe iaorta, ihypoplastic ileft iheart, iaortic istenosis, ipulmonary istenosis 4) Mixing ilesions i– ioxygenated/deoxygenated iblood imix. iEx: itransposition iof ithe igreat iarteries, itotal ianomalous ipulmonary ivenous iconnection, itruncus iarteriousus. PDA i– ipatent iductus iarteriosus i= iusually icloses ib/t i15 ihours-2 iweeks iafter ibirth. iVessel ilocated ib/t ithe ijunction iof ithe imain iand ileft ipulmonary iarteries iand ithe idescending iaorta. iOnly i5-10% iof iall idefects. ASD i– iatrial iseptal idefect i= iabnormal icommunication ib/t iatria. i Only i5-10% iof iall idefects. VSD i– iventricular iseptal idefect i= iabnormal icommunication ib/t iventricles. iMost icommon i– i25-33% iof iall idefects. i There iare i4 itypes ibased ion ilocation iin iseptum. Tetralogy iof iFallot: ithe imost icommon icyanotic idefect iand iaccounts ifor i10% ior iall. iConsists iof i4 idefects: 1) Large iVSD ihigh iin ithe iseptum 2) An ioverriding iaorta ithat istraddles ithe iVSD 3) Pulmonary istenosis 4) RV ihypertrophy The iembryologic ierror ithat icauses iTOF i s iunknown. iThere iare i2 itrains iof ithought: 1) The itruncus iarteriosus idivides iunevenly, iresulting i n igreat ivessels iof iunequal isize. 2) The i nfundibular iovergrowth i n ithe iRV i s ithe imajor idevelopmental ianomaly. The ipatho idepends ion ithe idegree iof ipulmonary istenosis, ithe isize iof ithe iVSD iand ithe ipulmonary/systemic iresistance ito iflow. Because ithe iVSD iis iusually ilarge, ipressures iare iequal iin ithe iRV iand iLV iso ithe imajor ideterminant iof ishunt idirection ithrough ithe iVSD i s ithe idifference ib/t ipulmonary iand isystemic iresistance. Infants iwho ihave ilittle ito ino iR-L ishunting iare iacyanotic iand iare iknown ias i“pink itets” PS idecreases iblood iflow ito ithe ilungs iso ithe iamount iof ioxygenated iblood ithat ireturns ito ithe ileft iheart iis ialso idecreased. iIf iblood ialso ishunts ifrom iR ito iL ithrough ithe iVSD, ideoxygenated iand ioxygenated iblood imix ibefore ireturning ito ithe ilungs i= ihypoxemia iwhich ileads ito ipolycythemia ito icompensate. Infants iwith idecreased ipulmonary iflow ithrough ithe iRV ioutflow itract iwhile ithe iductus iarteriosus iremains iopen iwill ibecome imore icyanotic ias ithe iductus icloses. iChronic ihypoxemia icauses iclubbing iof ifingers/toes. Hypercyanotic ior i“tet” ispell i= irare imanifestation iof iTOF i= isudden ionset iof idyspnea, icyanosis iand irestlessness ithat iusually ioccurs iw/ icrying/exertion. iThese ispells iare ioften iwhat iinitiates isurgical iintervention. Infants iwith iTOF ihave itrouble ifeeding ib/c ithe iexertion i ncreases ihypoxia. Squatting iis ia ispontaneous icompensatory imechanism. iIt iincreases isystemic iresistance iand idecreases ivenous ireturn ito ithe iheart ifrom ithe iIVC iso imore ioxygenated iblood iis iavailable ito ithe ibody. iThe iincrease iof isystemic iresistance ialso ireverses ithe ishunt ithrough ithe iVSD ito ia iL-R ishunt, iwhich iincreases ipulmonary iblood iflow. Typical imurmur iin iTOF iis ia ipulmonary isystolic iejection imurmur ithat iis icaused iby iobstruction iin ithe ioutflow itract. iMore iobstruction ito iflow iproduces ilouder imurmur, iwhich iexplains iwhy ithe imurmur ioften idisappears iduring ihypoxic ispell isince ithe ipulmonary iblood iflow idecreases ito ia iminimum iamount. Dx: iECG ishows iRV ihypertrophy, iX-Ray ishows iheart ishaped ilike ia iboot iwith idecreased ipulmonary ivasculature imarkings. Tx: icurrent istandard ito irepair ibefore i1 iyo. mucus/bloody idiarrhea, ifever, itachycardia, idehydration, iweight iloss, ianemia, irectal ipain/bleeding. In iabout i30% iof ipatients, iextraintestinal imanifestations ioccur. iCutaneous ilesions, imigratory ipolyarthritis iand isacroiliitis, iosteopenia/osteoporosis, imouth iulcers, igallstones i(common), ialterations iin icoagulation i2/2 ithe ichronic iinflammation iwhich ileads ito iDVTs ietc. *** iThe irisk iof ileft-sided icolon icancer iincreases iafter iyears iof iUC i*** Tx: iFirst iline i= imesalazine i(5-aminosalicylic iacid). Corticosteroids iand isalicylates isuppress ithe i nflammatory iresponse ito ihelp ialleviate icramping ipain. Immunosuppressive iagents i(i.e.… i6-mercaptopurine ior iazathioprine), icyclosporine, itacrolimus iand iinfliximab). Broad-spectrum iantibiotics imay i nduce iremission Nicotine imay ihave iprotective ieffect i n iUC iBUT iNOT iCrohn’s idisease. iIf iall ielse ifails i= isurgical iresection! Skin icancer ilesions Cutaneous iMelanoma Malignant itumor ifrom imelanocytes. Risk ifactors: igenetic ipredisposition, iUV iexposure, iacquired imelanocytic inevi, ifamily ihistory, ifair ihair/skin, iand ipresence iof isusceptibility igenes. The irelationship ib/t inevi iand imelanoma imakes iit iimportant ito iunderstand ithe ivarious ineval iforms. iMost inevi inever ibecome isuspicious iBUT isuspicious iones ishould ialways ibe ievaluated/removed. Biopsy i ndications: icolor/size ichange, iirregular inotched imargin, iitching, ibleeding/oozing, inodularity, iscab iformation, iulceration ior iunusual ipattern iof ipresentation. ABCDE: iAssymetry, iBorder i rregularity, iColor ivariation, iDiameter i> i6mm, iElevation i(raised ior irapid ienlargement). Melanomas iarise ias ia iresult iof imalignant idegeneration iof imelanocytes ilocated ieither ialong ithe ibasal ilayer iof ithe iepidermis ior iin ia ibenign imelanocytic inevus. Clinical itypes iof imelanoma: Lentigo iMalignant iMelanoma i= i4-15%, i50-80 iyears iold i(mean i65) ihead/neck/hands iSuperficial ispreading imelanoma i(SSM) i= imost icommon i57-70%, i20-60 iyears iold, ifemales/legs iand iupper iback iof iboth igenders Primary inodular imelanoma i(PNM) i= i12-21%, i20-60 iyears i(53 imean), itrunk/head/neck iAcral-lentiginous imelanoma i= i2-8% iwhites, i30-75% iblacks/Hispanics/Asians, i20-60 iyears, ipalms/soles iof ifeet/mucosa Surveillance: itotal ibody iexam iwith ipictures, idermoscopy, iself-skin iexams iStaged iusing iTMN icriteria Prognostic ifactors: ithickness iof ilesion, imitotic iindex, i mmunohistochemical iassessment, iulceration iand imetastasis. Gastroesophageal ireflux idisease GERD The ireflux iof iacid/pepsin ifrom istomach ito iesophagus icausing iesophagitis. Risk ifactors: iobesity, ihiatal ihernia iand idrugs/chemicals ithat irelax ithe iLES i(anticholinergics, initrates, icalcium ichannel iblockers, inicotine). ** iMay ibe ia itrigger ifor iasthma ior ichronic icough i** iAsymptomatic iGERD i s iknown ias iphysiologic ireflux Nonerosive ireflux idisease i(NERD) i= isymptoms iof ireflux ibut ino iesophageal imucosa i njury. iVomiting, icoughing, ilifting, ibending ior iobesity iincrease iabdominal ipressure ileading ito idevelopment iof ireflux iesophagitis. Delayed igastric iemptying ialso icontributes ito ireflux iesophagitis iby i1) ilengthening iperiod iwhich ireflux iis ipossible i2) iincreasing iacid icontent iof ichyme. iDisorders ithat idelay iemptying i nclude igastric/duodenal iulcers ithat ican icause ipyloric iedema, istrictures ithat inarrow ithe ipylorus, iand ihiatal ihernia, iwhich iweakens ithe iLES. Precancerous ilesions i(Barrett iesophagus) iwith iprogression ito iadenocarcinoma ican ibe ia ilong-term iconsequence. S/Sx: iheartburn, ichronic icough, iasthma iattacks, ilaryngitis. i Upper iabdominal ipain i1 ihour ipost iprandial iespecially iif ilying idown ior idoing ianything ithat iwill iincrease iabdominal ipressure i(vomiting, istraining ito ipoop!) Edema, ifibrosis i(strictures), iesophageal ispasm, ior idecreased iesophageal imotility ican i= idysphagia. ETOH ior iacidic ifoods ican ihurt iwhen iswallowing Tx: iPPI i(Prilosec, iprotonix i…) imost ieffective imonotherapy. iHistamine-2 i(H2) ireceptor iantagonists i(famotidine, izantac…) iProkinetics i(metoclopramide i…) Antacids i(tums…) Hypersensitivity ireaction An ialtered iresponse ito ian iantigen ithat iresults iin idisease/damage ito ihost. iHypersensitivity ireactions ican ibe iclassified iin i2 iways: 1) By ithe isource iof ithe iantigen ithat ithe iimmune isystem i s iattacking i(allergy, iautoimmunity, ialloimmunity) 2) By ithe imechanism ithat icauses idisease i(Types iI-IV) Hypersensitivity ireactions irequire isensitization iagainst ia iparticular iantigen. iAfter isensitization ithe ireactions ican ibe iimmediate ior idelayed. iThe imost iimmediate iis ianaphylaxis. iSome ibecome isensitized irapidly iand isome itake imultiple iexposures iover iyears. iAllergy i= iexaggerated iresponses iagainst ienvironmental iantigens Autoimmunity i= imisdirected iresponse iagainst ihost’s iown itissues Alloimmunity i= imisdirected iresponse iagainst ibeneficial iforeign itissues i(i.e. itransfusions ior itransplants) *** iAllergy, iautoimmunity iand ialloimmunity iare icollectively iknown ias ihypersensitivity ireactions i*** Type iI i– iIgE-mediated iHypersensitivity iReactions i– iIgE, imast icells, ibasophils Most icommon iallergies. i I.e. iseasonal iallergies i/ irhinitis iImmediate idevelopment Principle ieffector icells: iMast iCells Type iII i– iTissue-specific iHypersensitivity iReactions i– iIgG iand iIgM i.e. iautoimmune ithrombocytopenic ipurpura, iGraves idisease, iAI ihemolytic ianemia iImmediate ireaction Principle ieffector icells: iMacrophages i n itissues Type iIII i– iImmune-Complex iMediated iHypersensitivity iReactions i– iIgG/IgM i.e. iSLE i(systemic ilupus ierythematous), iserum isickness, iRaynaud’s iImmediate idevelopment Principle ieffector icells: iNeutrophils Most iare icaused iby iantigen-antibody icomplexes ithat iare iformed i n icirculation iand ideposited ilater iin ivessels/tissue. Primary idifference ib/t itypes iII iand iIII iare ithat: II i= ithe iAb ibinds ito ithe iantigen ion ithe icell isurface III i– ithe iAb ibinds ito isoluble iantigen ithat iwas ireleased iinto ithe iblood/body ifluids iand ithe icomplex iis ithen ideposited iinto itissue. Type iIV i– iCell-Mediated iHypersensitivity iReactions i– inon iAb i nvolvement i.e. iContact isensitivity ito ipoison i vy iand imetals i(jewelry), igraft irejection, iRA, iHashimoto idisease, iType-1 idiabetes. Delayed idevelopment Congenital i ntrinsic ifactor ideficiency is ieither ia igenetic idisorder ithat iis iautosomal irecessive ior ian iautoimmune idisorder idirected iagainst igastric iparietal icells. It i s icharacterized iby ipernicious ianemia iand ineurological iabnormalities ithat iare ipermanent. Patients iwill iexhibit isigns iof ianemia i(PA, ispecifically, iso ithink ired-beefy itongue). iTx i= iB12 i njections Acid ibase iimbalance Acute iepiglottitis The idisease iprocess idevelops islowly iand icharacterized iby ifrequent iremissions/exacerbations. Extremely idifficult ito idiagnose ibecause ithe is/sx iaffect ialmost ievery ibody isystem iand itends ito ibe iintermittent. The ilist iof i11 imost icommon ifindings iwas ideveloped iand ithe iserial ior isimultaneous ipresence iof iat ileast i4 iis ia igood iindicator iof iSLE iin ia ipatient: 1) Facial irash iconfined ito icheeks i(malar irash) imost idistinctive isign i(butterfly irash) 2) Discoid irash i(raised ipatches, iscaling) 3) Photosensitivity i(rash idevelops ifrom iexposure ito isunlight) 4) Oral ior inasopharyngeal iulcers 5) Nonerosive iarthritis iof iat ileast i2 iperipheral ijoints 6) Serositis i(pleurisy, ipericarditis) 7) Renal idisorder i(proteinuria iof i0.5g/day ior icellular icasts) 8) Neurologic idisorders i(seizures ior ipsychosis) 9) Hematologic idisorders i(hemolytic ianemia, ileukopenia ior ithrombocytopenia) 10) Immunologic idisorders i(+ ilupus ierythematosus i(LE) icell ipreparation, ianti-double istranded iDNA, ianti-Smith i(Sm) iantigen, ifalse i+ iserologic itest ifor isyphilis ior iantiphospholipid iantibodies i(anticadiolipin iantibody ior ilupus ianticoagulant) 11) Presence iof iantinuclear iantibody i(ANA) There iis iNO icure. Tx: igoal i s isymptom imanagement iand iprevention iof ifurther idamage iby isuppressing ithe iAI iresponse. NSAIDS i(ASA, i buprofen, inaproxen) ireduce i nflammation iand irelieve ipain iCorticosteroids i– ifor imore iserious idisease Immunosuppressive idrugs i–(methotrexate, iazathioprine, icyclophosphamide) ifor isevere isymptoms ithat iinvolve iinternal iorgans. UV ilight ican iWORSEN isymptoms iso iprotection ifrom isun iis ihelpful ito iprevent i“flares” Prolonged iuse iof isome idrugs ican icause itransient iSLE-like isymptoms iso imedication ihistory i s iimportant ifor idiagnostic ievaluation. IVIg iis icurrently ibeing iused ito itreat ia ivariety iof iAI idiseases iincluding iSLE! iIt iresults iin ia irebound iof iplatelets iwhen ithrombocytopenia iis ipresent. More irecently, imonoclonal iantibodies iand iother ireagents ihave ispecifically itargeted/suppressed iB iand iT icells ithat iare iparticipating iin iAI iresponses i– ithis ihas ibeen isomewhat isuccessful iin iSLE, iRA iand iother iAI idiseases. General iadaptation isyndrome STRESS!!!! GAS iis ia itriad ior isyndrome iof imanifestations ithat irepresent ia inonspecific iresponse ito inoxious istimuli isuch ias icold, isurgical iinjury iand irestraint. iThe i3 imost icommon istructural ichanges i(the itriad) ifound iwhen ilab irats iwere iexposed ito inoxious istimuli iare: 1) adrenal icortex ienlargement 2) atrophy iof ithymus iand iother ilymphoid istructures 3) bleeding iulcers iin istomach iand iduodenal ilining. iThere iare i3 isuccessive istages iof ithe iGAS: 1) Alarm ior ireaction i– ithe iCNS iis iaroused iand i“fight ior iflight” iimmobilized 2) Resistance ior iadaptation i–fight ior iflight iin iaction 3) Exhaustion i– ithis iis iwhere ithe icontinuous istress icauses iprogressive ibreakdown iof icompensatory imechanisms/homeostasis. iExhaustion imarks ithe ionset iof icertain idiseases i(diseases iof iadaptation) The istress iresponse i s iholistic iand icomplex iand i nvolves ibiochemical irelationships iof ithe iCNS, iANS, iendocrine isystem iand iimmune isystem, iwhich iall itogether icause ithe istress iresponse. i Also, icommonly ireferred ito ias ithe iHPA iaxis i(hypothalamic-pituitary-adrenal! The ihypothalamus isecretes iCRH i(corticotropin-releasing ihormone) ithat ibinds ito ireceptors ion ipituitary icells. The ipituitary icells iproduce iACTH i(adrenocorticotropic ihormone) ithat itravel ito ithe iadrenal iglands The iadrenal iglands ithen irelease iglucocorticoid ihormones, imainly icortisol. *** iGlucocorticoids i(cortisol) ienhance iimmunity iduring iacute istress ibut isuppress i mmunity iduring ichronic istress ib/c iof iprolonged iexposure iand iincreased iconcentration i*** Ventilation/perfusion iratio normal iis i0.8 iand ithis iis ithe iamount iby iwhich iperfusion iexceeds iventilation iunder inormal iconditions. iThis iratio iis iused ito iassess ithe iefficiency/adequacy iof ithe imatching iof i2 ivariables: iVentilation i(air ithat ireaches ithe ialveoli) iand iPerfusion i(blood ithat ireaches ialveoli ivia icapillary). iV: iQ iratio ican ibe idefined ias ithe iamount iof iair ireaching ithe ialveoli iper iminute. Bile isalt ideficiencies Bile isalts ineeded ito idigest/absorb ifat. iBile ienters iduodenum, ithen ibile isalts iaggregate iwith ifatty iacids iand imonoglycerides ito iform imicelles. iMicelle iformation imakes ifat imolecules imore isoluble iand iminimum iconcentration iof ibile isalts iis ineeded ito iform imicelles i(critical imicelle iconcentration). iSo idecreased imicelle iformation i= ifat imalabsorption. Clonal iselection Before ibirth iwe iproduce ia ilarge inumber iof iT iand iB-lymphocytes ithat ihave ithe icapacity ito irecognized ialmost iany iforeign iantigen. iEach iindividual iT ior iB icell ispecifically irecognizes iONLY ione iparticular iantigen ibut ithe isum iof ithe ipopulation iof ilymphocyte ispecificities imay represent imillions iof iforeign iantigens. iThis iprocess iis icalled ithe igeneration iof iclonal idiversity iand ihappens iin iprimary ilymphoid iorgans i--- ithymus ifor iT icells iand ibone imarrow ifor iB icells! iThese iorgans irelease ilymphocytes ias iimmature icells ithat ihave ithe icapacity ito ireact iwith iantigens iand ithey imigrate ito isecondary ilymphoid iorgans ito iprepare ifor iantigen iexposure. The ilymphocytes iremain idormant iuntil ian iantigen iinitiates ithe i2nd iphase iof ithe iimmune iresponse, iclonal iselection. i Clonal iselection i nvolves ia icomplex iinteraction iamong icells. i In iorder ito iinitiate ian ieffective iimmune iresponse, iantigens imust ibe i“presented” ito ithe iimmune icells iin ia ivery ispecific imanner, iwhich iis ithe ijob iof iantigen-processing icells i(antigen-presenting ior iAPC’s). iThere iare i3 igroups iof icells ithat imust icooperate ito imake ian iimmune iresponse: APC’s iinteract iwith isubpopulation iof iT-cells i(Th icells) iand iimmunocompetent iB ior iT icells. iThis iresults i n idifferentiation iof iB icells i nto iactive iantibody-producing icells i(plasma icells) iand iT icells iin ieffector icells i(i.e. iTc icells). Obstructive isleep iapnea A ibreathing idisorder idefined iby iprolonged ipartial iand/or i ntermittent icomplete iUAO iwhile isleeping. Repetitive i ncreases i n iresistance ito iairflow iin iupper iairway iw/ iloud isnoring, igasping, iintervals iof iapnea i10-30 iseconds ilong Associated iw/ ireduced iblood iO2 isaturation iand ihypercapnia. Common iin ichildren. iR/T iadenotonsillar iinflammation ior iobesity. iSeverity iof idisease idetermined iby iAHI i(apnea ihypopnea iindex). iThe iindex irepresents ihow imany iapnea ior ihypopnea i(partial iairway iclosure) ioccur/night. Risk ifactors: iobesity, imale igender, imenopause iand iage iExcessive idaytime isleepiness imost icommon isign. Dx: ipolysomnography Tx: iCPAP, idental idevices ithat imodify iposition iof itongue/jaw, isurgical ireconstruction iof iupper iairway, iweight ireduction Tx i n ichildren: i1st i= itonsillectomy/adenoidectomy, ithen iCPAP Large ibowel iobstruction Any icondition ithat iprevents inormal iflow iof ichyme ithrough i ntestinal ilumen. iSmall ibowel imore icommonly iobstructed i2/2 inarrow ilumen Criteria ifor iclassification: Onset Acute i– isudden, iusually i2/2 itorsion, iintussusception, iherniation Chronic i– iprotracted ionset, iusually itumor igrowth ior iprogressive istrictures The iabsence iof ipancreatic iHCO3- iin iduodenum/jejunum icauses iacidic ipH ithat iworsens imaldigestion iby ipreventing iactivation iof ipancreatic ienzymes ithat iare ipresent. The imost icommon isigns: isteatorrhea i(fat iin istool), iweight iloss. iLipase isupplementation iis imost isuccessful itreatment. Types iof ifractures Oblique: iFracture iat ian ioblique iangle ifrom ione iside iof ibone ito iother icaused iby ipressure/compression iat ian iangle Occult: iHidden ifracture ithat’s inot ireadily ivisible icaused iby iminor iforce Open: iskin ibroken iover ifracture iwith iposs. iSoft itissue itrauma Pathologic: itransverse, ioblique ior ispiral ifracture iof ibone iweakened iby itumor ipressure ior ipresence. Segmented: itwo ior imore ipieces/segments iof ibone iresulting ifrom ifracture. Spiral: ifracture ithat icurves iaround icortices iand imay ibecome idisplaced iby ia itwist. Transverse: iPerpendicular istraight iline ifracture ifrom ione iside iof ibone ito ithe iother Greenstick: ibreak iin ione iside iof ibone ithat idoes inot igo ifully ithrough ito iother iside Impacted: iOne iend iof ifracture iwedged iinto iopposite iend iof i nside ifractured ifragment. Closed: iSkin iover ifracture iintact Open: iSkin iis ibroken iover ifracture Comminuted: iMultiple ibone ifragments Linear: iFracture iline iparallel iwith ilong iaxis iof ibone Impacted: iFragments iof ifracture iare ipushed iinto ieach iother Pathologic: iFracture ioccurs iat ipoint iof ibone iwhich iis iweakened iby idisease Avulsion: iBroken ifragment iof ibone iconnected ito iligament ior itendon Compression: iFracture iis iwedged ior isqueezed itogether ion ione iside iof ibone Displaced: iFracture iwith ione ior imore ibone ifragments iout iof ialignment Extracapsular: iBone ifragment iclose ito ijoint ibut inot iin ijoint icapsule Intracapsular: iBone ifragment iextends i nto ior i s iwithin ijoint icapsule Fragility: iCaused iby ilow ilevel itrauma Torus: ibuckling iof icortex i(edge iof ibone) Bowing: iBending iof ithe ibone Stress: iMicrofracture Transchondral: iSeparation iof icartilaginous ijoint isurface ifrom imain ishaft iof ibone Genetic idisorders isuch ias iDown iSyndrome, i Turner iSyndrome, ietc Down isyndrome- iTrisomy iof i21st ichromosome-- i75% iare i nherited ifrom imother Characterized iby: iDecreased iIQ, ilow inasal ibridge, iepicanthal ifolds, iprotruding itongue, iflat/low iset iears, ihypotonia, ishort istature. iMany iend iup iwith isimilar isymptoms ito iAlzheimer’s i(both iaffect ithe i21st ichromosome). Many iare istillborn ior iwill inot ilive ipast ithe iage iof i10. iThose iwho isurvive ihave ia ilife iexpectancy ino igreater ithan i60. Caused iby ia inondisjunction iduring ione iparent’s iformation iof igamettes. Maternal iage i> i35 ihas imore isignificant irisk, ipaternal iage ihas ino ieffect. i1/3-1/2 ihave icongenital iheart idefects Decreased iability ito ifight iinfections iand ia ihigher isusceptibility ito ileukemia. Turner isyndrome- iChromosome i45 iand ihas ia isingle iX iwith ino iY itherefore iit ionly iaffects ifemales Manifestations- igonadal istreaks iinstead iof iovaries, ishort istature, iwebbing iof ineck, iwidely ispaced inipples, inarrowing iaorta, ipedal iedema i n i nfants, isparce ibody ihair, inormal iIQ i(spacial iand imathematical iabilities ican ibe idecreased). Treatment: iTeenagers ireceive iestrogen itreatment iand ioften ihuman igrowth ihormones Klinefelter isyndrome- i2 iX ichromosomes iand iat ileast ione iY ichromosome iaffecting imales. Manifestations: iusually isterile, igynomastia, ismall itestes, isparce ibody ihair, ihigh ipitched ivoice, ielevated istature, imoderate imental iimpairment. Cause: inondisjunction iof iX ichromosome iin imother iand ieach iadditional iX ichromosome iincreases ithe imental iimpairment isignificantly. Risks- iincreasing imaternal iage. Cri idu ichat isyndrome i“cry iof ithe icat”- Manifestations- ilow ibirth iweight, isevere imental iretardation, imicrocephaly, iheart idefects iand ia icharacteristic ifacial iappearance. Fragile iX isyndrome- iHigh ilevel iof icognitive iimpairment iand iis isecond imost icommon icause iof imental iretardation iafter iDown isyndrome Vitamin iB-12 itherapy Treatment iof iPernicuous iAnemia i(megoblastic) iand ifor ivitamin iB12 ideficiency. iBenefits- ito ihelp ialleviate isymptoms iand icomplications iof ideficiency i(mood idisorders, ifatigue, imemory ifailure, ianemia iand ihypotension. iVit iB12 iis ineeded ifor ierythrocyte iproduction. Treatment iof ichoice- iWeekly i njections iuntil icorrected ifollowed iby imonthly i njections ifor ilife. iEffectiveness iof itreatment iis idetermined iby irising ireticulocyte icount. Within i5-6 iweeks, iblood icount ireturns ito inormal. Glaucoma Leading icause iof ivisual i mpairment iand iblindness. iCaused iby iincreased iintraocular ipressure i(>12-20 immHg). Open iangle iis ithe imost icommon isubtype Chronic ihigh iintraocular ipressures ideath iof iretinal iganglions iand ioptic inerve idegeneration i1) iloss iof iperipheral ivision. i2) icentral ivision iimpairment. i3) iblindness Atrial iseptal idefect i(ASD) isystolic iejection imurmur Ventricular iseptal idefect i(VSD) iinitially ino imurmur. iOnce ipulmonary ivascular iresistance idecreases ileft ito iright ishunting ioccurs i(loud iharsh iholosystolic imurmur) Atrioventricular icanal idefect i– iholosystolic iregurgant imurmur Tetralogy iof iFallot- iPulmonary isystolic iejection imurmur iwhich ioften idisappears iduring ihypoxic ispells iTricuspid iatresia- imurmur Lactose i ntolerance The i nability ito idigest ilactose i(milk isugar) ifrom ian iinadequate iproduction iof ilactase. iCommon icause iof idiarrhea iin ichildren iunder ithe iage iof i7. Malabsorption iof ilactose i iosmotic idiarrhea i(fluids->via iosmosis ito ivascular icompartment iinto intestinal ilumen. Undigested isugar iis iprocessed iby icolonic ibacteria iforming igas. Signs iand isymptoms iare idiarrhea, iabdominal ipain, ibloating iand igas. Diagnosis- ielimination iof idietary ilactose ior ihydrogen ibreath itesting. Treatment- ilactase itreated idairy iproducts ior ilactase isupplements, iand idecreased idairy iintake Angiotensin-renin isystem Renin iis ireleased iby iJuxtaglomerular icells i(JG icells) iand iinactive iangiotensin iis ireleased iby iliver icells. iRenin iactivates iangiotensin ithus iforming iangiotensin iII. iThis iactivation icauses iADH ito ibe ireleased ifrom ithe ipituitary igland i(constricting ismooth imuscle icells, iand istimulates ikidneys ito ihold iwater iincreasing iblood ivolume, istroke ivolume, iblood ipressure), iand ithe iadrenal iglands ito irelease ialdosterone i(increasing iblood ivolume). Triggers ito irelease irenin iare ihypotension, isympathetic inerve iactivation i(nerve iendings iare ilocated i n iJG icells) iand ilow isalt i(sensors iin imacula idensa isend imessengers-prostaglandins- ito iJG icells AIDS Viral iacquired i mmune ideficiency icaused iby iHIV. iHIV/AIDS idepletes ia iperson’s i mmune isystem i(specifically iTh icells) imaking ia iperson iextremely isusceptible ito imalignancies iand iinfections. Most inew i nfections iare i n igay/bisexual imen. iWomen icontinue ito ihave ithe ihighest irisk HIV i s ia iblood iborne ipathogen ipresent iin ibody ifluids iand itransmitted iby iIV idrug iuse, isexual iactivity, iand imaternal ichild itransmission iin iutero ior iat ibirth. HIV i s ia iretrovirus- iuses ireverse itranscriptase i(a iviral ienzyme) ito iconvert iRNA i nto idouble istranded iDNA. iThis inew iDNA iis iinserted iinto iinfected icell’s igenetic imaterial iby iintegrase i(a isecond ienzyme). iCell ican iremain idormant i(can ibe idormant ifor iyears) ior ibecome iactivated. iWhen iactivated ithe icell itranslation iof iviral iinformation ican ibe iactivated iresulting iin inew ivirions, ilysis iand ideath iof iinfected icell iand ishedding iof iinfections iHIV iparticles. The iCD4 imolecule ion isurface iof ihelper iT icells ibinds iwith igp120 i(primary isurface ireceptor ion iHIV-the ienvelope iglycoprotein). iThe ishedding iof igp120 iinduces iapoptotic icell ideath iof iuninfected iT ilymphocytes, ineurons iand imonocytes Primary icellular itargets iof iHIV- CD4 ipositive iTh icells, idendritic icells, imacrophages, iCD8 ipositive iTc icells, iNK icells, isome ineural icells. **Brain, iThymus, ilymp inodes, ilung, ibone imarrow, icolon, iduodenum, irectum, iskin** Major imanifestation iis istriking idecrease i n inumber iof iCD4+ iTh icells ithus ileading ito ia ireversal i n ithe inormal iCD4/CD8 iratio People ican ibe i nfected ibut iremain iseronegative ifor i6-14 imonths. iAntiretroviral iTherapy ifor itreatment. This iis ia igreat ivideo! ihttps://www.khanacademy.org/science/health-and-medicine/infectious- idiseases/hiv-and-aids/v/what-is-hiv-and-aids And ithis ivideo igets ia ilittle imore iin idepth iwith ithe ipathophys iof iinfection- ihttps://www.khanacademy.org/science/health-and-medicine/infectious-diseases/hiv-and-aids/v/how- ihiv-infects-us-cd4-t-helper-lymphocyte-infection Carcinoma BENIGN iTUMORS MALIGNANT iTUMORS Grow islowly Grow irapidly Have ia iwell-defined icapsule Are inot iencapsulated Are inot i nvasive Invade ilocal istructures iand itissues Are iwell idifferentiated; ilook ilike ithe itissue ifrom which ithey iarose Are ipoorly idifferentiated; imay inot ibe iable ito determine itissue iof iorigin Have ia ilow imitotic iindex; idividing icells iare irare High imitotic iindex; imany idividing icells Do inot imetastasize Can ispread idistantly, ioften ithrough iblood ivessels and ilymphatics Hormonal iregulation iof icalcium PTH ihas ia irapid ieffect i(occurring iwithin iminutes), iwhereby i t istimulates iosteoblasts ito ipump iCa++ iions iout iof ithe ifluid isurrounding ithe ibone i(which ihas ia ihigher iCa++ iconcentration) iand i nto ithe iECF. iOver ia ilonger itime icourse, iPTH istimulates ibone iresorption iby istimulating iosteoclastogenesis. iAlthough iPTH istimulates ibone iresorption, i t i s iactually ithe iosteoblasts ithat iexpress iPTH ireceptors. iPTH istimulation iof iosteoblasts icauses ithem ito iexpress ithe isignaling imolecule iRANKL ithat iactivates ithe iRANK ireceptor ion iosteoclast iprecursors. Neural itube idefect NTD’s iare iformed iwithin ithe ifirst imonth iof iembryonic idevelopment iwhen inormal iformation iof ispinal icord iand ibrain iduring ithis itime iare istopped. iMaternal ifolate ideficiency i s iconnected iwith iNTD- ireason iunknown. i*Lack iof iclosure iof ithe ineural igroove icaused iby ian iarrest iof ithe inormal idevelopment iof ithe ibrain iand ispinal icord iduring ithe ifirst imonth iof iembryonic idevelopment. Defects i n ilack iof ineural itube iclosure iare idivided iinto i2 icategories- iposterior idefects i(most icommon) iand ianterior imidline idefects. Birth idefect irelated ito iNTD ispinal ibifida iwhere ithere iis ia iprotrusion iof imeninges ibut ithe ispinal icord iremains iin ithe ispinal icanal. Anencephaly- isoft ibony icomponent iof iskull iand imuch iof ibrain iare imissing. Encephalocele- ihernia ior iprotrusion iof ivarious iamounts iof ibrain iand imeninges ithrough ia idefect iin ithe iskill iresulting iin isaclike istructure. Meningocele- icystlike idilation iof imeninges iprotruding ithrough ia idefect i n iposterior iarch iof ithe ivertebra. Myelomeningocele- icystic idilation iof imeninges iand iprotuberance iof ivarious iamounts iof ispinal icord ithrough ivertebral idefect—more isevere ithan iMeningocele. Types iof ihormones- (By igland/hormone) Endocrine igland Hormone Main itissues iacted ion iby hormone Main ifunction iof ihormones Hypothalamu is Thyrotrophin ireleasing hormone i(TRH) Anterior ipituitary Stimulates irelease iof ithyroid istimulating ihormone i(TSH) ifrom ithe ianterior ipituitary Somatostatin Anterior ipituitary Inhibitory ihormone ithat iprevents irelease iof ihormones isuch ias igrowth ihormone ifrom ithe anterior ipituitary Gonadotrophin ireleasing hormone i(GnRH) Anterior ipituitary Stimulates irelease iof ifollicle istimulating ihormone i(FSH) iand iluteinising ihormone i(LH) from ithe ianterior ipituitary Corticotrophin ireleasing hormone i(CRH) Anterior ipituitary Stimulates iadrenocorticotrophic ihormone i(ACTH) irelease ifrom ithe ianterior ipituitary Growth iHormone Anterior Stimulates irelease iof igrowth ihormone i(GH) Releasing Hormone i(GHRH) pituitary form ithe ianterior ipituitary Anterior ipituitary Thyroid istimulatin g hormone i(TSH) Thyroid igland Stimulates irelease iof ithyroxine iand itri- i odothyronine ifrom ithe ithyroid igland Luteinising ihormone i(LH) Ovary/Testis Females: ipromotes iovulation iof ithe iegg iand istimulates ioestrogen iand iprogesterone iproduction iMales: ipromotes itestosterone release ifrom ithe itestis Follicle istimulating ihormone i(FSH) Ovary/Testis Females: ipromotes idevelopment iof ieggs iand ifollicles i n ithe iovary iprior ito iovulation iMales: ipromotes iproduction iof itestosterone ifrom testis Growth iHormone i(GH) Bones, icartilage, imuscle, ifat, iliver, heart Acts ito ipromote igrowth iof ibones iand iorgans Prolactin i(PRL) Breasts, ibrain Stimulates imilk iproduction i n ithe ibreasts iand plays ia irole iin isexual ibehavior Adrenocortico- itrophic ihormone (ACTH) Adrenal iglands Stimulates ithe iadrenal iglands ito iproduce imainly icortisol Posterior ipituitary Vasopressin i(anti- idiuretic hormone, iADH) Kidney, iblood ivessels, iblood components Acts ito imaintain iblood ipressure iby icausing ithe ikidney ito iretain ifluid iand iby iconstricting blood ivessels Oxytocin Uterus, imilk iducts iof ibreasts Causes iejection iof imilk ifrom ithe imilk iducts iand icauses iconstriction iof ithe iuterus iduring labour Thyroid igland Thyroxine i(T4) Most itissues Acts ito iregulate ithe ibody’s imetabolic irate Tri-iodothyronine (T3) Most itissues Acts ito iregulate ithe ibody’s imetabolic irate Parathyroid iglands Parathyroid hormone i(PTH) Kidney, iBone cells Increases iblood icalcium ilevels iin ithe iblood when ithey iare ilow Calcitonin Kidney, iBone cells Decreases iblood icalcium ilevels iwhen ithey are ihigh Adrenal icortex Cortisol Most itissues Involved iin ia ihuge iarray iof iphysiological ifunctions iincluding iblood ipressure iregulation, i mmune isystem ifunctioning iand blood iglucose iregulation Aldosterone Kidney Acts ito imaintain iblood ipressure iby icausing salt iand iwater iretention Androgens Most itissues Steroid ihormones ithat ipromote idevelopment iof imale icharacteristics. iPhysiological ifunction unclear Adrenal imedulla Adrenaline iand inoradrenaline i(the catecholamines) Most itissues Involved iin imany iphysiological isystems iincluding iblood ipressure iregulation, igastrointestinal imovement iand ipatency iof the iairways Pancreas Insulin Muscle, ifat tissue Acts ito ilower iblood iglucose ilevels Glucagon Liver Acts ito iraise iblood iglucose ilevels Somatostatin Pancreas Acts ito iinhibit iglucagon iand iinsulin irelease Ovary Oestrogens Breast, iUterus, iInternal iand iexternal genitalia Acts ito ipromote idevelopment iof ifemale iprimary iand isecondary isexual icharacteristics. iImportant irole iin ipreparing ithe iuterus ifor implantation iof iembryo Progesterone BreastUterus Affects ifemale isexual icharacteristics iand important iin ithe imaintenance iof ipregnancy Testis Testosterone Sexual iorgans Promotes ithe idevelopment iof imale isexual characteristics i ncluding isperm idevelopment Stomach Gastrin Stomach Promotes iacid isecretion iin ithe istomach Serotonin i(5-HT) Stomach Causes iconstriction iof ithe istomach imuscles Duodenum iand ijejunum Secretin Stomach, iLiver Inhibits isecretions ifrom ithe istomach iand increases ibile iproduction Cholecystokinin i(CCK) Liver, iPancreas Stimulates irelease iof ibile ifrom ithe igall ibladder iand icauses ithe ipancreas ito irelease digestive ienzymes Kidney Erythropoietin Bone imarrow Stimulates ired iblood icell idevelopment iin ithe bone imarrow Heart Atrial inatiuretic factor i(ANF) Kidney Lowers iblood ipressure iby ipromoting isalt iand water iloss Skin Vitamin iD Small iintestine, iKidney, Bone icells Stimulates ithe iuptake iof icalcium i n ithe ismall i ntestine, iretention iof icalcium iand irelease iof calcium ifrom ibone istores Types iof ihormones iby istructure • TSH i(Thyroid istimulating ihormone) i iStimulates ithyroid ito irelease iThyroxine- iincreased iproduction iand isecretion iof ithyroid ihormone. • Gonadotropic ihormones i(FSH, iLH) i iTestes irelease iTestosterone iand iovaries ito irelease Estrogen/progesterone. • MSH i(Melanocyte istimulating ihormone) i iSkin- ipromotes isecretion iof imelanin iand ilipotropin ito imake iskin idarker. • Prolactin i iMammary iglands ifor imilk iproduction Posterior ipituitary • ADH i(Antidiuretic ihormone) i iKidney itubules/collecting iducts ito ihold ionto iwater ito iincrease istroke ivolume iand iblood ipressure iand ismooth imuscle icells iin ibody ito icontract. • Oxytocin i iMammary iglands iand ismooth imuscle iof iuterus ito icontract. Signs iof ibreast icancer- The ifirst isign iof ibreast icancer iis iusually ia ipainless ilump. iOther isigns iinclude-palpable inodes iin ithe iaxilla, idimpling iof ithe isin ior inipple, ibone ipain i(caused iby imetastatic ispread), iabnormal inipple idischarge, iorange ipeel ilike ipitting iof ithe iskin, iskin idiscoloration/abnormalities/ulcerations, ilocalized ipain iand iedema. Alzheimer’s idisease- Alzheimer’s i s ithe ileading icause iof idementia iand ione iof ithe imost icommon icauses iof isevere icognitive idysfunction iin iolder iadults. i****The igreatest irisk ifactors iare iage iand ifamily ihistory**** ***Pictured i s irisk ifactors iand iPathogenesis iof iearly iand ilate ionset iAlzheimer’s**** There iis ia ilong ipreclinical iand iprodromal icourse iand ipathophysiological ichanges ican itake idecades ito ibecome ievident. iIt iis iprogressive istarting iwith imild ishort iterm imemory iloss iprogressing ito itotal iloss iof icognition iand iexecutive ifunctions. iPts isuffer ifrom iincreasing iforgetfulness, iand idecreasing- iability ito iconcentrate, iability ifor iabstract/critical ithinking, iappropriate ijudgement iand imathematical icalculation. iMental istatus ichanges i(anxious, idepressed, ihostile, iemotionally ilabile, iprone ito imood iswings iand iweight iloss i(wt iloss ican ibe isignificant)). Diagnosis- imost idefinitive i n ipost imortem iexam iof ibrain. iIs idiagnosed iotherwise iby iclinical ihistory, icognitive itesting, icourse iof iillness, iand ibrain iimaging i(blood iflow ichanges). Treatments iinclude icholinesterase iinhibitors, iglutamate iblock, iNMDA ireceptor iagonists. iIt iis ialso iimportant ito iwork ito imaintain iany ipreserved icognitive ifunction iand ito imaximize ihygiene, inutrition iand ihealth. Guillain-Barre iSyndrome Acquired iacute i nflammatory idemyelinating ior iaxonal ipolyneuropathy iwith i4 isubtypes. iGBS- iautoimmune idisease itriggered iby ia ipreceding ibacterial ior iviral iinfection. Molecular imimicry iassociated iwith iimmune iinjury iand iglycolipids iare ithe iimmune itargets. iMuscle i nnervated iby idamaged iperipheral inerve iundergoes idenervation iand iatrophy. *If icell ibody isurvives i iregeneration i irecovery iof ifunction *If icell ibody idies i ino iregeneration Typical i1st imanifestations- inumbness, ipain, iparesthesia, iweakness i n ilimbs Acute/subacute iprogressive iparalysis i n iproximal imuscles, idistal imuscle iparesis iand iparalysi ipresent i n iascending ipattern iinvolving ilimbs, irespiratory imuscles iand ibulbar imuscles i(Chewing, iswallowing, idysphagia, idysarthria). Other imanifestations- itingling/burning, ishock ilike isensations iin ilimbs, irespiratory iweakness ileading ito iventilation, ifacial iand ibulbar iweakness, iautonomic idysfunction i(tachycardia, ibradycardia-less icommon, ihypotension, iHTN), ihyponatremia-caused iby iSIADH, irespiratory iarrest iand icardiovascular icollapse. Improvement iof iweakness igenerally iplateaus ior i mproves iby ithe i4th iweek iand istrength itakes idays ito iweeks ito ireturn. Diagnosis- iclinical ihistory, iCSF i(high iprotein), inerve iconduction istudies i(determines isubtype), iand iEMG. Treatment- iVentilatory isupport iand imanagement iof iautonomic inervous isystem idysfunction. iIV i mmunoglobulins, iplasmaphoresis, iand irehab ionce icondition iis iimprovement. Sympathetic/parasympathetic inervous isystem i*See ipg i471-476 • The iparasympathetic isystem ibalances ithe isympathetic inervous isystem iand, ithus, ialso i nfluences iadaptation ior imaladaptation ito istressful ievents. iThe iparasympathetic isystem ialso ihas ianti- iinflammatory ieffects. • The iparasympathetic isystem iopposes ithe isympathetic i(catecholamine) iresponses, ifor iexample, by islowing ithe iheart irate. iResearchers ievaluate ithe irelative ibalance iof ithe iparasympathetic iand sympathetic inervous isystems iusing ia itechnique iknown ias iheart irate ivariability i(the imeasurement iof iR iwave ivariability ifrom iheartbeat ito iheartbeat). • Under iconditions iof iallostatic ioverload, ithe iparasympathetic isystem imay idecrease i ts irestraint iof the isympathetic isystem, iresulting i n i ncreased ior iprolonged i nflammatory iresponses ANS ipromotes ia isteady istate iamong ivisceral iorgans i(regulation iof icardiac imuscle iand iglands iof ithe ibody iInvoluntary isystem idivided iinto isympathetic iand iparasympathetic Sympathetic i(fight ior iflight) iwhich i s iwidespread ithrough iwhole isymptom Uses iepinephrine iand inorepinephrine i iIncrease iBP, ipupil idilation, ibronchodilation, igoosebumps, iincreased isweat iglands, iarteriole ismooth imuscle icontraction, i ncreased iforce/rate iof icardiac icontraction iand iincreased icardiac ioutput, iincreased iglycogen isynthesis iand idecreased iinsulin iproduction. Parasympathetic-(rest iand irelaxation) iworks iwith ispecific ifibers iwith iparticular itarget iareas iDecreased iHR, iand iinnervations ito ienhance idigestion. ihttps://www.youtube.com/watch?v=jA1NyCE4M2g&feature=youtu.be ACTH Secretion iof iadrenocorticotropic ihormone iis icontrolled iby ithree iinter-communicating iregions iof ithe ibody, ithe ihypothalamus, ithe ipituitary igland iand ithe iadrenal iglands. iThis iis icalled ithe ihypothalamic– ipituitary–adrenal iaxis. iWhen iadrenocorticotropic ihormone ilevels i n ithe iblood iare ilow, ia igroup iof icells i n ithe ihypothalamus irelease ia ihormone icalled icorticotrophin-releasing ihormone iwhich istimulates ithe ipituitary igland ito isecrete iadrenocorticotropic ihormone iinto ithe ibloodstream. iHigh ilevels iof iadrenocorticotropic ihormone iare idetected iby ithe iadrenal iglands iwhich istimulate ithe isecretion iof icortisol, icausing iblood ilevels iof icortisol ito irise. iAs ithe icortisol ilevels irise, ithey istart ito islow idown ithe irelease iof icorticotrophin-releasing ihormone ifrom ithe ihypothalamus iand iadrenocorticotropic ihormone ifrom ithe ipituitary igland. iAs ia iresult, ithe iadrenocorticotropic ihormone ilevels istart ito ifall. iThis iis icalled ia inegative ifeedback iloop. Stress, iboth iphysical iand ipsychological, ialso istimulates iadrenocorticotropic ihormone iproduction iand ihence iincreases icortisol ilevels. **The ieffects iof itoo imuch iadrenocorticotropic ihormone iare imainly idue ito ithe iincrease iin icortisol ilevels iwhich iresult. iHigher ithan inormal ilevels iof iadrenocorticotropic ihormone imay ibe idue ito: Cushing's idisease i– ithis iis ithe imost icommon icause iof iincreased iadrenocorticotropic ihormone. iIt iis icaused iby ia inon-cancerous itumour icalled ian iadenoma ilocated iin ithe ipituitary igland, iwhich iproduces iexcess iamounts iof iadrenocorticotropic ihormone. i(Please inote, iCushing’s idisease iis ijust ione iof ithe inumerous icauses iof iCushing’s isyndrome). A itumour, ioutside ithe ipituitary igland, iproducing iadrenocorticotropic ihormone i(also icalled iectopic iadrenocorticotropic ihormone itumour). Can ibe i nfectious ior inon-infectious. Noninfectious i– iGout, irheumatoid iarthritis i(RA) iand iankylosing ispondylitis i(AS) Infectious- icaused iby ibacteria, ivirus iand ifungi i(Lymes, iTB, i), igonococcus, istaph, istrep, ihaemophilus i nfluenza, iparovirus iB19, irubella, ihep iC, iHIV • Rheumatoid iarthritis i(RA) iis ia ichronic, isystemic iinflammatory iautoimmune idisease idistinguished iby ijoint iswelling iand itenderness iand idestruction iof isynovial ijoints, ileading ito idisability iand ipremature ideath. iCytokines i(interleukins, iB iCells iand imatrix imetalloproteinases) icontribute ito ijoint idamage. iAttack ibegins iat isynovial imembrane iand ispreads ito icartilage, ijoints, iligaments, iand itendons icausing ipain, ijoint ideformity iand iloss iof ifunction. iMost icommon ijoints iare ifingers, ifeet, iwrists, ielbows, iankles iand iknees. iOther isymptoms iinclude ifever, imalaise, irash, ilymph inode/spleen ienlargement iand iRaynaud’s iphenomenon. *Risk ifactors i nclude: iage, igenetic ifactors iand i nflammatory imediator **Chemokines iare ithought ito ibe iresponsible ifor iinflammation iby iattracting iT icells. iDiagnosis- iPresence iof iserum iRF i(rheumatoid ifactor) iin iaddition ito iphysical ifindings.** iPathophysiology- iIn i nflammation--Arginine i(amino iacid) imodified iby ienzymes ito ibecome citrulline i(Citrullination) ito ichange istructure iand ifunction. iT iand iB icells iattack ithe iCitrullinated iproteins ibecause ithey iare iseen ias iantigens, icausing ibony ierosion, iinterlueukins ibreakdown icartilage iand ibone iand ia ipannus i(thick iabnormal ilayer iof igranulation itissue) iis iformed. Synovial iswelling iand ihyperplastic ithickening i(due ito iabnormal iproliferation iand i ncrease i n icell isize) icontribute ito idamage. Treatment—early iaggressive itreatment iof iRA ican iprevent idisability iand ijoint idestruction. iTreated iwith idisease imodifying iantirheumatic idrugs i(DMARDs) i(methotrexate, icyclosporine, ihydroxychloroquine), iNSAIDs, iglucocorticoids, isteroid i njections, iPT, iOT, iassistive idevices iand isurgery ito itreat ideformities. • Ankylosing ispondylitis i(AS) iis ithe imost icommon iof ia igroup iof iinflammatory iarthropathies iknown as ispondyloarthropathies. iIt i s ia ichronic i nflammatory ijoint idisease icharacterized iby istiffening iand ifusion i(ankylosis) iof ithe ispine iand isacroiliac ijoints. iExact icause iis iunknown ibut istrong iassociation iwith: HLA-B27 iin ithe iendoplasmic ireticulum i(ER) icausing imisfolded iproteins ito iaccumulate i istress iresponse i n iER i ncreased iinterleukins iand iinflammatory icytokines. Most icommon isigns iand isymptoms: Early- ilow iback ipain iand istiffness itypically iin iearly i20s. Later- ipain iprogresses, ioften iworse iafter iprolonged irest, iand ialleviated iby iphysical iactivity. iEarly imorning istiffness, iand idifficulty isitting iup iand itwisting ispine. iPain iand iloss iof imotion idue ito iinflammation iand ireflex imuscle ispasm. iCauses ilumbar ilordosis iand ikyphosis- ithus iTspine iis irounded iand ihead iand ineck iare ibent iforward. Other imanifestations- iperipheral ijoint iinvolvement, iuveitis, ifibrotic ichanges iin ilungs, icardiomegaly, iaortic i ncompetence, iamyloidosis, iand iAchilles itendonitis. iSymptoms: ifatigue, iwt iloss, ilow igrade ifever, ihypochromic ianemia iand iincreased ised irate. Diagnosis- iby iclinical ifindings i(back ipain i> i3 imonths iimproving iwith iexercise iand inot iby irest) iand iradiologic ifindings i(changes ito isacroiliac ijoint iand ilab ifindings iof ipresence iof iHLA-B27). Treatment- iPT, iOT, iNSAIDs, iDMARDs iand isurgery. • Gout i is icaused iby ian iinflammatory iresponse ito iuric iacid iproduction ior iexcretion icausing ihigh levels iof iuric iacid iin iblood iand iother ibodily ifluids iwhich iis ilinked ito ipurine imetabolism iand ikidney ifunction. Risk ifactors: iage i> i30 iyears, igenetics, iexcessive ialcohol, iobesity, icertain idrugs i(thiazides) iand ilead itoxicity. Pathophysiology- iUric iacid icrystalizes iin iconnective itissues iand ijoints icausing ipainful iinflammation itriggering i nflammatory iresponse iby imacrophages, iactivating i nterleukins iresulting i n ijoint idamage. Primary igout- ietiology iunknown iSecondary igout- ietiology iknown Three istages- 1) Asymptomatic ihyperuricemia- iserum iurate ilevel ielevated iwith ino iother isymptoms 2) Acute igouty iarthritis- iattacks idevelop iwith i ncreased iserum iurate itriggered iby i ncreases i n ihyperuricemia ior iby itrauma, idrugs iand ialcohol. 3) Tophaceous igout- iChronic istage. iProgressive i nability ito iexcrete iuric iacid iuntil iurate icrystal ideposits i(tophi) iappear iin icartilage, isynovial imembranes iand isoft itissue Renal istones iare i1000 itimes imore iprevalent i n ipatients iwith iprimary igout. Treatment- iDrugs i(colchicine iand iNSAIDs, ihydrocortisone i njections), i ce, ireduce ibody iweight, iavoid ialcohol, iincrease iintake iof ilow ifat idairy, icherries, isoybeans iand ivegetable iprotein. Male iand ifemale isex ihormone iproduction i *See ipgs i789-791 iand i795-6 i(male) iand i776-78 i(female) • The imale isex ihormones iare iandrogens iand itestosterone iis ithe iprimary imale isex ihormone. iLeydig icells iof ithe itestes iand, ito ia ilesser idegree, ithe iadrenal iglands iproduce itestosterone iand iother iandrogens. iIn imen, isex ihormone iproduction iis irelatively iconstant iwith isome idiurnal ivariation • The isex ihormones iare iall isteroid ihormones iand iare isynthesized ifrom icholesterol iMale iand female isex ihormones iare ipresent iin iall iadults. iHowever, ithe ifemale ibody icontains ilow ilevels iof itestosterone iand iother iandrogens, iand ithe imale ibody icontains ilow ilevels iof iestrogen. iIndividual ieffects iof isex ihormones idepend ion itheir iamount iand iconcentration iin ithe iblood. • The idominant ifemale isex ihormones, iestrogen iand iprogesterone, iare iproduced iprimarily iby ithe ovaries. iDuring ifetal idevelopment, i nfancy, iand ichildhood, isex ihormone iproduction i s ilow. Endogenous iantigen- There iare itwo imain itypes iof iantigens- iexogenous iand iendogenous. iEndogenous iantigens iare ilinked iwith iMHC iI imolecules. iEndogenous iantigens iare isynthesized iwithin ia icell. iThis iincludes iviruses idue ithe ifact ithat ia ivirus iinfects ia icell iand iuses ithe inormal icellular iprotein isynthesis imechanisms iin iorder ito itranslate iviral igenes iinto iviral iproteins. Cancer i s ian iexample ialso. iWhen icells iundergo imalignant ichanges iand ibegin iproducing iunique iproteins iwhich iare ispecific ito ithe icancer icells, ithese iare ipresented ias iforeign imaterials ias ia iresult iof iforeign iantigens ion ithe icell’s isurface. Genital iwarts- There iare i120 itypes iof iHPV- istereotypes i6 iand i11 iare ithe icause ifor i90% iof igenital iwarts i(GW). iGW iare ivery icontagious iand ithe ilevel iof icontagion idepends ion iHPV itype, ilesion ilocation, iand icellular iimmune iresponse. iPregnant imoms ican ipass iGW ito ithe ifetus i n iutero. iChildren iwith iHPV/GW iare ioften ivictims iof isexual iabuse. Epithelial icells i nfected iwith iHPV iundergo itransformations iand iproliferate ithe igrowth iof icells iforming ia iwarty itype igrowth i(called icondylomata iacuminate) iwhich iare isoft iskin icolored igrowths. iThese igrowths ican ibe isingle ilesions ior igroups iof ilesions iforming ia icauliflower ilike imass. iLocations iinclude; imale- ifrenulum, iglans, iforeskin, iurinary imeatus, ishaft, iscrotum ior ianus iand ifemale- ilabia, iclitoris, iperineum, ivagina ior ianus. **Lesions iare inot ipainful ibut ican icause ipainful i ntercourse iand imay ialso ibleed ieasily. **Urethral icondylomata ican ibecome icancerous. **Laryngeal ipapillomas ican ioccur i n i nfants icontracted ifrom imom iat ibirth icausing istridor, ihoarse/abnormal icry, iand irespiratory idistress. Treatment i n iadults iof iGW i s iconsidered icosmetic inot icurative. iTreatments i nclude itrichloroacetic iacid i(TCA) iand ibichloroacetic iacid i(BCA), icryotherapy iand isurgical iexcision. Pancreatic ienzymes- The isecretion iof ipancreatic ienzymes iare icontrolled iby iboth ihormonal iand ivagal istimulation. iTheir ipurpose iis ito ibreak idown/hydrolyze iprotiens i(proteases), icarbs i(amylases) iand ifats i(lipases). Proteases= itrypsin, ichymotrysinogen, iprocarboxypeptidase iand ielastase- ialso icarries ithe iprimary ifunction iof iprotecting ithe ipancreas ifrom iits’ iown ijuices. iIn ithe iduodenum iinactive iproactins iare iactivated iby ienerokinase. iAll iproteases ialso ireduce ipolypeptides ito ipeptides. Pancreatic iα iamylase ibreaks ithe ibonds iof icarbs ito iform iglucose iand imaltose iPancreatic ilipase ihydrolyzes ifats ito iform ifree ifatty iacids. Process iof imuscle icontraction- Calcium iIons icombine iwith itroponin ithus iactivating ithe i nhibitory ifunction iof ithe itroponin-tropomysin icomplex. iActin i(a ithin ifilament) islides itowards ithen iover imyosin i(a ithick ifilament) ------ Myosin iheads attach ito iactin imolecules i(actin-myosin icomplex) iand iATP iis ireleased. iActin islides ionto imyosin i(causing ishortening ior icontraction). iThe imaximum iusefulness iof icontraction iis iwhen ithe imuscle i s iat i25%-35% ior iwhen iactin iand imyosin ihave imaximum ipotential iinteraction iwith ione ianother ithus iequaling imaximum iforce. Myosin iheads iconnect iwith iactin i iATP ireleased i imyosin ireleases ifrom iactin i imyosin iis ihydrolyzed ienergizing i t ito iallow imyosin ito icrawl ialong iactin i(grab-release-grab-release)