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Groziveseu 12 logy book is designed to provide F disease proovases and altered heal paragraphs, by using key concept boxes, and icon consider compauion for students daring ca is also a refresher to resident, practitioner and graduate students ‘why and wherefore of almonnal concerned pathophysiology"s place ason as os NOLLWRINY LUNI JO SLDII9 WWALSAS "FE ce 7 supaaad aaiivarivnd Zee SIDRIAG TALVLUNVTD Vet "HOLM UOLVINIY LIN a SAOVIS MOLLYNEIPTINE LADY = OTOIS: eudLavHo. errata aulesour'sy2 ~ oem YA YFLLOMLAH CEDMONE PPT —oomnnnn § ddd VIABALLOUA EE oom Sass RN THLLVSN JO S3ONBNDASNOD TEL ~ ADO1OHF ONY NOLINLERE- EE oF orUaHAasANF Te eerre eee ‘SIS Tabu AE 912 F 8 NAD NIA F TE 7 ; SBOVIS WaAds V1 c ADO NOISANUONIVA Aa CTT cans ‘53S ASIC ITAA JO NOUWOUISSD ~ ADOOUA ONY NOIR HIN = wana re noenneenarnennnnn gat HOSIE SURLY UTUEVIL AOA E "7 WALA SudUOSTO GALV1AY 3DY ANY ONIDY 40 ADOTOISA i SASNOASY ONY S133448 KUO wren SNOLLYDIXDINI TEL SVASIE AO L909 MLE : NOMDAGOUENET ADOTOISANAOHLVa NI SLd8NO9 TVUANAS "TE 1 usavHo SLNGLNODOPROVEINENMAS. x 7” PEILIPOMROTEINEMIAS. Sees 88 471.6. PATHOPHYSIOLOGY GF CHRONIC COMPLICATIONS xeon 103 422, 1YPOGLICEMIA, 8 QUALITATIVE PLATELET DISORDERS. 8 ABLE STATES, CHAPTER 6 = ABE 6. RED BLOOD CELLS DISORDERS, soo BSL 61, ANEMIRS cee meen : rn ANEMAS CAUSED RY IMPAIRED PRODUCTION OF ERYTHROCYTES I : oS JENCY one 16 OF HEMATOPOIETIC SIEM CELLS IROID PROGENITOR CELLS... 136 IZED BY IMPAIRED DNa SYNTHESLS ci ans Bs 6.114. IMPAIRED HEMOGLOBIN SYNIHESIS: DISORDERS CHARA WED ENZYMOPArT os - 6.1.23, HEMOLYTIC ANEMIAS CAUSED BY EDU 6.1.24. HEMOLYTIC ANEMIAS CAUSED DY al THE RED BLOOD CELL : 5.13. ANEMIA FOLLOWING BLOOD LOSS. 6.14. DILUTIONAL FSEUDOANEMLA... 62. POLYCYTHEMIAS : 02.1, APPARENT POLYCYTHEMA... 62.2 SECONDARY POLYCYTHEMIA eee : 152 623 POLYCYTHEMIA Vi EE c ern CHAPTER 7 a vA SS* xa0Nt - “ANAT ~ SANOUANKS NOISWILOUAIE S98 ADU TOISAHAOH La NOISNELO. “390uS TALIDIUISUO ZTSE SOOHS BINBODINIVD Bess AO0HS JaLuNANSIase5e we AOOHS JUENOADIAL PTSS ie mm OOIS AUDDVUY EES wr -AD0HS 40 SISWHE THWWNAGONAH TESS see i SNOUAEITY avLaTIBD 17S we ~ AOOONS.GMOLLGE 758 see NOWYOUISSYD ANY HOLINLEBE Tse see - “ ADOOISANJOHLYU 2045 8 Keo “0 Su NEODASNOD NOISNALIAGAIL FY # ao BROWGNAS VISSHNTDE-AMd NI NOISNELALUI E> 9 a “"WIIOY BELL JO NOLLWI9UVOD NI NOISNEDEUARL ECY8 a -20)XO ORLIN 01 3fa NOISNELEUAN 9CPS ee S¥ACUOSIG HOO TOW NI NOISNELAAE SPS ee ~~ SaNOMUOHE UARINRILYELOL ANG NOISNELURANIE VE 8 SHAUN TONDE LVS 40 N 2 04 ANG NOISNILNBIAIT'EEY'S oe se az siz’ aac aw ra sor at ast 6 ‘SXBGWOSIU GAY 19 TWNEYOV ML NOISNALWAIAEY TCS “NOIRE IAN Tee ROISNALYAAALL AIVANODaS CFS "= NOISNSLURUAN AUVHLNUE TE NOULYOUISSY1D NY NOLLEWAG Es DOTOISAHJOHL Yd NOWELL Fs D¥lauy9 Nequas sees WUVOUARCEETR SAMOYUNAS {CIVRONOD ALNY TEES ~ some" GRIOUSM YNIONY TEER SANOWONAS JUNBHOSL ECE ot wt Sst ot : ANLYEOANOMHYD CAL UG Te 7 enone LLY SOANONTAND 9119348 JO ADOIOISAHJORLLYE PETE ee STL LWA A SHONVAD WUT WEL ined La MH ONCGOHE aN AMaOMLUAAAIH AVINDMIUNAA EELS c AQoTOISATAOHLYA Tr NOLLYOUISSITD a0) a AO TOUA RUN LUV ~ é ADOOISANAOHINE TAUV LASTS SAMHOSIEUYINDSVAOTTWI —" @MILLAVIED SNOWONAS VERAGUAI-VANAY E2378 4A SMOG AUYNOH Z seormmnnme Sg ENOGSNOD TYOINTID ETPL AOOOISAHMONLLVA VME AYYNOHINA TFL “ASO 1OHLR ONY NOLLUNLSIO TCP yada aIYNOW INE v> ~~ gaswasten wr INOsvA Fe snip ith go sasvasia eee Ite AML 40 Sa5vasiG TE 7 agyasia ONT WILLSYBLN TCL Ee Sasvasid suOLaMAseR AAL ONS 6 7 on gS YLOTTALY PTE > sisvisateonoua © ~yausanuna ECE ~~ aSVaSIa /ALYNOWAM ALDAMLSAO DINO Cee : = = WHUSY IT ~ oor gagvasia AOU. WalasaH AAUDMLSBO TL oo pUTTIv AUOLY WES BUNDY ~ HOLWHISIW NOISNEYRI-NOLW LNA Pt 7 - “ANnns : navesrwaru soismsaia ECE “7 NOUN TLAREAOUAT VURAXOAAK AUOLYHIASTH 10 SA UNIV AUOII ‘suaaaosGeneral concepts CHAPTER 1 1, GENERAL CONCEPTS 1.1. INTRODUCTION -) of the function cnossmucroscnere TeaTuRESOF DISEASED ORGANS PATHOLOGY Figure 1: Differences between pathophysiology and pathology Pathophysiology also differs from pathogenesis, which desc developinent ofthe disease process. 1.2, THE CONCEPY OF DISEASE 65 constant balance in our internal environment th stats is called homeostasis. When there ‘offen causes a disease. Therefore, disease as a change in the normal body function that leads to an sbaore structure (fig.2). and structural disorders is not always fanctional disturbance without any sig 110 cholerae ink5 suopoqjut 98 2 s91qoq woq mot :93y yacjoq worveaa 24 °¢ 24Ne susixa uy (suon2aput ‘wou sowie y= snousifoxa “ sseasond eu rep a “sossaioud aseas1p Sousyqeiss eseamp ayy JO sisouaomed 2, ssoupubas ayroads 3! 2 frag ee Saas waigh in carbobydeate or eotucted fat intake, ver, iereased physial enetcise drei therapies, pr eed (o slit end orean req) 4 hich cesulls inthe physical symptoms oF and venous pressutes, These changes can lead to » i i Genera concepts 4. Onygen deficiency Myposia can result fro © decreased oxygen loquate amount of oxy tory disease sport of oxygen © ischemia (le, decreased blood flow caused by hearvcitculatory disoricrs) lar smelling caused by f un (Nes/K+) ATPase membra ‘oxyRen supply is not restored there is a eo vzymes, proteins, and ribonucleic ac 2©) Spoupaudl-< syoqerou ayy EMOHE YH Buywout “(pot sou 244, ysv2iq “Kamau josds ut Jays ston “ues as0dpe 211 sypo ewkususied ql apuaasiaiy ssooxo jo. suoHeMuInay = 2ynbe Frsne> sts aye suaneypas £4 p208 lu sogtumy> wows 944 s}>9 BuyAy oF ingusiey 99 ats suorTespes fo 90 seoype 3esh'a (ssuinuoray,a Kanfuy a0 nuyaa —__xuaenr Yi 4TsisuEAE, CR tHi® ) +@ ) yt @) + ° sees 1 tm | using aasavay aweeiox | : (sma 4-9 89) uojssusuantoanan ym Buna + “(sua fayi9 (e3tg) steep pao poser ue SosUIA poUUO) ApxoU yp UOMN et oOo, 292 sayayoad yests -B9) yEOP 190 & RNS AIST esngastonnnns sme Sen #2: Sanfuy summa,“ (122 poD|g pas 94s re8icos00 Sse] + ‘pueaquipun un egy Sasiin sahous ose) + wsuonzayuy > ceeds peiey 3). 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Sueus Ruyeaued © iS BIDhae can messenger level: + Abnormal number of receptors (c.g, down repul ly high abnormalities (22, fiom Vibrio el thelp it cope jon needed and deactivated when the 5 General concepts therogenesis postin as high blood pressut DB Allored colt size increased/decreased dem wsele strength increase only fre not dead and they can be react FOF Abroblasic growth factor, HGF = hepate growth Ovthfacion, POGF = plauclet derived growth freien fre induced by the ai © pathologic anatomy) any release of iammatory response is assot Jammnatory medistors (TNF-alpha) oy see spoptos10 pUe VNC 01 (SOx) Saidads UBBAxO san;eSL jo qoaya RaySeamp oxp pasodaid Zui yo Lioayp feapes veay aL sauiej0 fous wed oy ase Bide pus wedsay Luo vt Busy sry “peursuare 1 S35i89 3 suaawosia ¥ DNIDV AO ADOLOISAMAONLLV a TY kyo asen pjaraie ansaid suios oayis ssaoand a ' que Gowan payee Be 21) vious “asnedospae ‘asuadoyeies) sio}2ej 2uf120p19 0} ss ‘25001000 Oe Seeus 809 0 DeIpieD paseasmap S128 Apog oui sy SRI FIBE = ies SIS FEESBody temperature disorders CUAL OR 2 2. BODY TEMPERATURE DISORDERS (0 maintain the body core temperauste at the siamo v lan body temp (erent processes: behavioural voluntary =} teaenesin [i pivinoie Say teraperature disorders release of norepinephrine body temperature. ms in body temperature may seflect met accompanied by changes in b Fever use to be dei 1e temperature set pu Exogenous pyrogens are the lipopolysacc fe bacteria are pac spreeens are proinflammatory cylokines, most importa TNFalpha, and several medistore other 33pue souvuszeq epyndod sip saseasip sie SaSVASIC AUN 40 NOLLVOIAISSY1O 'C vzBody lemperature disorders FEVER STAGES: Before fever occurs, bT™= Tsp. Fever respouse progresses though three stapes 1. Fever easel (cotd stage) = bT- veh vasodilatation and eweating is activated blood temperature at the hypothalamic level ‘Tsp. Prolonged fever may decrease heart preload and cause ‘olyte misbalauces. When fever is resolved bl ~ Tsp a 2.1.5, PEVER BENEFITS The raged fre desteoyed aud so vital replica wretics should be used ouly wl Side effects are significa Body temperature disorders 2.1.6. FEVER (ARMPUL EFFECTS ue, joint pata and headaches, 5 disturbances of consciousness ium), even seizures in certain circumstances. A lever of 415°C is call very severe infections ar in those wi auiekly rhythms, 2.2, HYPERTHERMIA When the thermore develops lefect of the sarcoplas ot (halothane, — enlurane, (suxamet loride) cause sudden and excessive Ca? release fom the ve Consequence is generalized and never jeemetabolism (inereased ATP consumption) and f poneralized skeletal wwscle rigidity wer produce ATP. | lead 10 ineres respiratory neidosis along with lec Diood pressive. 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Visceral disease in type 3 is neatly ye 1 but is generally snore severe n le myoel tnmediary metabolisn disoders dev reticular ve pat Ivmphatfe vessels, aid pul leads to demise in adoleaeer 44, OTHER STORAGE DISEASES WILSON’S DISEASE Wilsow’s disease or hepatoten: isorder caused by mutations i lwansporting ATPase nd femoves excess coppe paired in Wilson's disease. Thp ‘and causes oxidative dam fibrosis (deposition of releases free copper into the bloodstream, the brain most capper ie deposit duces the neuropeychi © to copper deposition Kayser-Fleischer sings are be also associated. fenal tubular acidosis, which leads to rieanbrane, cousin Corulopiasmin is’ seeISOIBWONJOUIY UL HOSS UO : susiio 21p jo uorjeiuowiiid s2u01q @ Spey ae : SaRIe Seam ou eyaqdodosep ce yuo:sue4 ukydiodnesd oyarodaxyuers, pesreeypouss ‘as5piXe pax | (Ga) enAydiod seu, | (QL Ore) HaBouLKyd:odoyOud aupiodonara anedsy | waxydiodesdon éaenpsi91 Ud) see ORS ore; rousina cussing | (un) saRouersaasodon auedory qvedoy uedayt (vty) aiemyensiouruc-g SEATS ysis 9503) a taoese a1 vuisejd 249 ul uodsusy, Dlaay) 2 uu! (uaa sae yjve quasoid ‘psepixo yylodap-foddoo & “a sseydoyars9 iw foro, sackdon oofactors, amyloid damage of endath we of platelet, therapy-related hyper Misorder, (BONE DRATRNCTION cae fsttauexstonoua Tame JONES Jreorenivuea| chain deposition, amyloidesie, urate nept anti-inflemmatory agents, bisphosphonates), cont Hypercaleemi increased urinary stone * oecur in @ minority of patients, and may have many © hypercalcemia may produce lethargy, weakness, depression, and‘3/00 994 "LC nos “sofoqped }QXT da 3464 OU Sop AeaY| ay) JE = stone Joss9seyon UNAas Si9aye Ayoouip sionlocss Je't Jo Stes eogouny 20 saqaun ayy uy BURY soleus y "1017 91 pousauos aie qy 210u" pue “aE pu “fer1A su0UH soj2inss s94y)ssn803q uoRDMpo.d TC") paseeiON 6 ‘quElea EI Melt Sera OTaISTTOHSTOUN semuadzpody pauiguiod ywopusas (Sioa SVIMEINIALOWOdITUATAL AURA “E E> ost oz ost-oel 6et-our MrSwHTT peor og, POISED SN AIL :9 2IaRI, ons o0$-002 oys-08e ove > woe > apLLOh 'anay foraIsajoys-IC} PUR (D4) sopuD9yseN opisuo suonpoyissefa ys HHO) jorsys310H> suasmquu0} yp TELA sara nat nota tat act ops nonesai wysyoudody Hnnujpomodns oqreanrs weg, oak Sf 10 voweouisser> wos pesE =P TEL. 7 1 Augagonst aeaooxd B vO paseEq SI 54 pougap usaq ane sepeuopt cath Aarpuioms + 1.4 poser = QT Award nun e- rye tepwendysod rvayissots (ea!Soj079 24. pyoxdody 0} asa sopofout ITH IO ty sejaqued wiajoidedy synods yo suonrenvecuoa paienaia epsoaip ayjoanieis © at (qr) etwompsjosdody sod.iyg SVINENISLOUM OR TIBIA T9' RITMIOSHE WSVTOGVLAW GEE povandie wow smo] 21 SOL augers LloMqNl 9M 30 Sfaxay puE ppausuanop n55q ase] ANCL DHE DHA ‘9-11 11h Soups Goremuseyuront ou yo spss} 19 By ing “WeafDUN sf stsauaBoxped (saBueqs UES pu "Boast dow 0p9 jeclosniieAjod SUROIpUAS SURO “inoue Ose Aets enoursosdRsed jo addy yoos op ayypads suomHor}du09 93430) -Kdesayy raya apis # 8 Aycan {203095 ‘ojomtinsues 201jo pus uIpUS jerogdusd yo aoneqyuE © 9 De famon Jo 580] pur Spiny ayRSU ASAT,leaned metabo disorders the Knee and ankles). Barly cor omozygous condition, valvul are common secondary DL» Apo C&R , PL> VLDL. FFA <4 LPL» TG to MUSCL RDU & Ape C, PL. TG IDL Ck & HIDE FFA <4 LPLTG to MUSCLE / ascent HDL LeaT cob IDL, CHY- Apo C&E,, PL, CE MDL, @ Apo C CITY, ro ia is rare autosomal pecessivel ramoterized by hyperabsorption. ay leading to hypercholesteraieinia. Pr Coronary attery disease is associate, PLLTG LEAT 30+) fl (apo 100, apok) Liver < MDL, —» adrenal, gonadal Isolated elevation oF HDL, increase lougevi snd ensures proteton agin MI dus to the effects on vessel: a berets Figure 15: Endogenous lipoprotein pathway (C= chotesterol, 16= triglyceride, PL = phospholipids, LPLolgpoprot LCAT“tocithin cholestrol wey transferase) The taajor ap An clevated co yperatpatipo; secondary, and LDL receptors, ‘The scavenger pathways uptake by monasytes 4 tnd macrophages, leading to fv: deposition in the dissase ‘oxidized LDL, Expression ofthe gulated by cellular cholesterol ~ permitting massive has een demonstuted in ‘accurmulates in other areas, particularly the skin, causing i eyelids and a Variety of xanthomas (tubeious xa fon xanthoms on Aclilles tendons, extensor 10ce Taya e ws ppaysipoas-soudssau pasesioop pue sto;2o0as eh | Ju e asediy anedoy poonpey t posvarcap A aN, “suoREAe}e apLAOX|BUN PallOst 20 wynprdydy 91 Peat eus ose sueteso(2-YCT seamed stuDktursswisprosdipedin stsiproxiqpodsyy FMA. 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"WaHfoavie> pateanaep pee ran ues ik pasean 56 (enusurjuidedqod, Os ipordioAo ue fq poxyssHsep AL 2M) (OLB woprssosyataprediy preg Epos TR Kapaa cs ‘Kous}oyap wefan op 14-4344 v are sins Jo puowdeyaaap 24 uaa “usiproxtipodst weusioaid wounu 86 tore} ajqeurnoapr yeso!yppe UD sose0 298: Uy nod pu “seea54p reaoina meh vp gode Uy nonin (aay) eHmaayoselodueregacet souro1pudS weutouaromo(y> my 0 sinvea) = AilesOUDE B JoN s s[som[aeOMIS amueuIg “ayeBowuouay down, 20 ‘sewowjuex annémae “snpestourd dojeaap seAet -whaouorsqu| Peounowed pure yuaisised quis Muoped owice Suoseed UmewrUN 103 Wonsuiioy ICH pus “IGT seoMpes soMEsES|3 HOLD! Ssuureaioued Baimes sonnet ops) oFaH WoMn wurossUEN ase ‘ceoiousd sup wanonp aed sunt pee (aT) sami] wisioidodey ap sSumrpaks eruoussoimotsay eH, yosdydty suowazoxa 29} s2naty NYU NOUDUNOAHD > : ‘91 '3 ody > aH 9 S041 WIDSAW OF OL— 117 Svat NOWWURO LAH “14 GRO oly TCH t joudsoud + gparoty (eppsos8un tors1s9[099) CHa T AUVLAA TPREG eTIntermediary metabo disorders Nepliie syndrome is thought to increase hepatic synthesis of VLDL. and also ‘catabotigen of both LDL sad VLDL. Higher levels of proteinuria are 5. Drugs High-dose th Jide diurstios or elorthalidone 7 High-dose bets-adrenergie blocking agents (Oral estrogen replaceinent therapy Be ‘Oral enntraceptives with high estrogen content Glucocorticoids Atypical anlipsychotics. 6. Alcohol Excessive alcohol Intake leads to hypertiglyoetidemia due to: jets (60% of calorie ilake). ‘ay cause substan Boweves, ute pancre ‘Coun trnetio 1 causes bolesterol excretion, and apolipoprotein X synthesis, les by eased gut cholesterol synthesis, iy-to-mederately elevated Wiglycerides in th state pregnancy Iypecipemia may ocr er Ravironmestal fa levels HDL concentrations: O History of aleohol ase S Tyentment with medications soch ae oml estrogens, phenytoin, or Horas, © History of vigorous, sustiued aerobic exercise (es, distance romui'g) Teduces Tevels of HDL cholesterol, shille quitting ads to arse i the plasma HDL level sapregne lone 4.6.13. HYPERLIPOPROTEINEMIAS CONSEQUENCES Consequences of the hyperlipoprotsinemias are caused by the deposition of id Extreme elevations of Uiglycerides, ust well above 1000 ni/dL. (exceed 4 lotermedi metabolism disorders ° Orsnge-yellow discolaraiious af the some Cases are raised; considered ° areus » This occurs infreg ° welasma - These are pale yel ‘They appeae infrequen erythematous base. They are most prc jocks, chest, and proximal extremities, caused ns af chylomicrons within macrophages end rear gradually when tiglycerides ate kept below 1000 smg/Al.. These typically painless skin Tesions may become pu © When tisycerides are ately and massively elevated, physical findings a be absen nduscopic exanai He eee ais is primarily caused by an elevation of the serum, le Jevels, which imparts a milky color to the blood. The ¢ usually not seen until the triglyceride level reaches al least They are best observ Hy appear salmon- pal, fel rises further, they become wh periphery. progress toward iting the avteries fiom the veins is difficult. The findings can Nuctuate widely from day 10 éay, depending on yoeride level. The fundus aboraalities, which improve as the triglyceride levels retum to normal, provide @ method of fotlowing the patient's course and response to therapy. 4.6.2. HYPOLIPOPROTEINEMIAS Lecithin cholesterol aeyltransferase (LCAT) (LCAT catalyzes the formation of chotesterol esters in lipoproteins) deficieney has two for LCAT deficiency in which there is complete LCAT 8s8 sour 5 roaqh Jo sustueyoou yp HLVa SISONTIISOWHLY CES sojesnjoone wojsisd.g, jauodaiva aanesapsord pup “ 21348 1 eae SuaHed 250g) Jo SUM “sSeIeMRIOR—N, foana ‘s¥ojonop Sisses satay suonenucsues ssoany8 suoiquie 391) o» 9Ane;S! mo} B18 sana] ag “fppede> Kojsi998 et We 7 ads Je) Jo Unopavon, paseaiouy pus“ ‘uot, po}eA3— anaisuaiy asban13 paseai2ap 0} spen "eased uy spioe Sy) 90] fo Sfon3t paves OL 209 Say yosu “SuE}}on UYREU] 99 Bag eared 24) Sy asuodeaL nbbspeut ue pu zeny ay ue “ay “2.25000 UL souensiau so asneroq sin=oo f4gensn Aowaroysp mneM Dayerae 7 28 WU ATHUOTTG wry ENT rotted 54 4c 1eotay s0p ys1 ayy ‘9He Banos we asada sip 29 r9I88 anOy WAC) 1 aU FosUO-maUE YN SHUAKTEM Jo YAO YROaY “Ayn naI0aK PIED oNSeYUL jean ‘uROONE Ue sursjuos suas © 31 (aoHoaiuy stiaot4esxOD pu sesnia samen uo pasnocy sey uonuape ayNUos se posoduid uesg onsy sursoy pu 1p Se Gans s10%065 oredouge 4 wa (at suo L24iO -samAyy 94 rd 01 sepndoe a4 : | 9399 sant, #20} peop “9 suiosoulosys jo we 04s "soul WH yea 23099) 1 pe ez0}08j suneayonTE pL = uo Sugsoy poreadar Lq paunguoa oq pynoys a SyoqeaU 19497 2809 Jandyi-e, “awa ote nse LLDO ( (iva) stoniean 2isqrip par “(Lop saueisyoi ss0sart paapeduny (at) a80amf8 Bonsey pazedsey :sapu08oye9 NsouzeIG =e ONE, ipousoyn 9982p OF POLED Dee (191) suer9[0} B00] |—soroqjnsp-21d jo sutiny ova “san0%ays9 |Bopu4} ese} 0} WOMIPPE WL yom Se saiogeip { 24) ayoudionid uve Aoueuioud ‘o4se590 uo ‘Saraqe4p on ous uf sdorenap saioqeip 1 2d ‘sized azo 0) Siaaau (SAemye you 19g) op sayy “Yead sup pear (Paatnap esi! pareioosee-Kouwezord way 20 poaaas a1 Jruoyeso8 Burney se 9 que usuioy “Koueueud Sump pojsoyop iy #130 exeadie yoy 20121240), niyijour soyoquip feuoneysss 9 fou0s 10d *sielonsAp oroAuL ‘owospass paye-woopy-sousiner| “Sseep sau iponig "suiaapus suleyjo,y “‘ouoepads 301% “quipus ‘usec "F-2) sowoxpucsTu ye 2 DM resus frm compl texpresion a whieh ised 15 diabeogeni leave (ey excessive cals adversely affect glucose meisbotism: ly acid levels secelerste hepatic gluconeogenssia, muscle glucose metabolism, and impair pancreatic Pecell hevefore, hyperglycemia. Insulin concent = absonce of ketosis. level of glycemia, AL least 6 genetically different types of MODY have been described, Some ely require insulin to contol glycemia. 47.13, PATHOPHYSIOLOGY OF FASTING CHANGES. Type? DM cansiot be explained by any singe pathogenic mectansm jy TM The deng bree i Ne prope hom none g tolerance to IGT to frank type 2 DM is progressive loss of insu] secretory eapaciy Once type? DM becomes mifece ast ie Ievels in type 2 DM goncraly eppesr nal or slevate, yet ty cly low given the degree of coexiaing hypeglyecia. A’ the Uiseate progress and hyperycemin becomes Jn both type 1 and type 2 DM, fasting hypergtycemnia results mainly from a ‘inppropriate increase in hepatic glucose production due mestly 10 accelersied genesis. The less of insulin’s rest jrease in portal glucag. of glycogenie substrates to glucose Aeficieney in type 1 DM leas to overwhelm renal seemaval mechauistns ‘ition to hyperglycemia, fasting free Fatty acid levels are also elevated in PM because of arcelerated mobilization of fal stores. In type 1 DM ma LAY ids are more readily converted to Ketone bodies, Daring etoacidosis, keto ibetic levels are further increased because of the concurrent rele vormones. Glucagon levels rise, acessot Ia SILMIAROLed pw sprroredas Supntons gory) Bat JO worm} paonpu-usaA/HadAy Kq podsup at key set 2Ys,“SHaaN TEMAS 30 ssoy PUB HONDTINY (ana) JOLIN jem AC JO S08 Ayes yedoun anaqeiey pecomT sq T Buisraiaop, rePPsoMIAUIOTS 1 Biuped| on “S609 JOY “soo0/% Jo Tena} eseydood pun “saponred uyeyoudod! npr 1D aseany ue 20fjed perw.s7a900 we pue (spy) stomport pu 8 seroods u28:éxo anqjonaz yo ayyonposd pesvatout Pus sis yeyotpopos “B'3) uosenIaDUOD 35001 Suronpond dq syosuaduros 0) sidure w ssneasq qwnsn CHEV € 1 Apiea uy seasp asoonys pooja 39g ‘susyp2q Te sja42] 260aN|8 pooTa PasEAAOM 10 eUIOU Ka po2LID}ORRN $f sopaquip | 2d gir sm999 uoustouayd ponogal 10 woRamoUNR 1 FOLYDISIA, ehydration => Wigure 17: Hypergyeemia effects 47.1.5, PATHOPHYSIOLOGY OF ACUTE METABOLIC COMPLICATIONS. Metabolic deeampensal syndromes, diabetic ketoacidosis (DKA), syndrome (HFS) or hypoglycemia, hyperosmolar hyperglycemic ino, Intermediary metabolisn disorders 4. DIABETIC KETOACIDOSIS DKA may herald the onset of Gisketie patients ae» resul Iypergiveemia. Other common clinical amorexia. Abcominal pain in the setting of DKA is classical mimic an acute abdomen, Reduced motility of the gostviniestin ‘oses, paralytic tlens may furlher contribute to digguostc confusion, Vo fminate eyreptoo beca éepletion ey flow ration end ac secondary to 14 mncens membran, rediced ale Typotention, depressed en toms. Ketosis may ba recognizable by © Dochemical features of DIKAhyperycem sis—sesult from the combined effects of tticlen ei ory hormones. ‘These itslanges mabiize the delivery of substrates fam maecl (ons tous, ical pyrovate) and adipons tse Choe ay ais, paced Ts caved rat, nectoacetnte, acetone). Bath are ltinetely elas tras tha really exceed he capi of tse ote en reult ate Iypergieemia (2250. mg (pli = 130) Fyneralyeonia induces an eemato. dives hat pomes dtytatin ms electrolyte loss. eee sor 16 ketone bodies (ft into the 2. HYPEROSMOLAR IYFERGLYCEMNC SYNDROME (HIS) The liars ofthe HBS ere severe hyperesmelarity 2320 moun.) and bypergvsemia 600 madly Severe nypergyexmia vars because patents cannot di seep pace wit a gwen soma werion eventvally Re aes 10 remarkable. blood fs Incase concentrations are ge 7 tosis are generally absent in the HHS. This is expleined by sso capacity remain sufficient to suppress Kipolysis and y jon. However, some type 2 patients with Sepressed enGogenoiis insulio secretion may he ‘nable to suppress. Ketonea suoyeraye Sreupnenusg ‘oeypiea uappns pu “ayiey y8u eIpaedepes Bays ogy mop poe e Sed Seu pus soieqep _eatonuy 2 este ue> ‘some BUOY poe ‘Baio AywaHe> sayoy ‘Saar [PIPOH pi Jour SoS jusaedeaws qusuboss “Pua issaioud mmo}s "suo [ENP a10W si? 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JO aus <4) 38 uusgY Jo uoHREMES a4) puE UsquION [E99] Jo LONE=UO soype)) waydimc aseuiquionjead ey. HO A 4OIDRI BULL BA LODE] “A. 201035 use pes oasis waLsnouo3, “seas dD woesion SuBpuq weBougy wa voyetarae jeuonIppe Jo WaWINASAL pUE AAA eIBSE|E pUMICG ype waqeld aygissascis, wy Suyyasss Agora “UoTENMOsUOD AHO be oy eanoour ue ux xe[dkuos ett emtgn avepine wyeneyd 242 spRatCD LONER via (Cy saeNoquIANY! 'wDSey[o9 H's) Sanlu mIOOSEA JO OUS aN Te payESUAE pasodi SioWe} IO “UoHIABeoa uu pIoMPeId UguONA “(eeHRdouIdD “aay Be) uoyeanee ue 5 oy patee(as asuode “AKANE elses ESP SGTHemostasis disorders Hesysigsis alsorders a Hirnaiscisorgens an adjunct for management after coronary angioplasty, can also cause platelet dest the ge of fone by ¢dp-nvees stato neta inug-induced structural chang: Aiaease comparable to adult TT. fonulsting ofthe drug and a porton of the cane drugs have been studied, antigens that have been defined involve the major report an increased incidence of Hl pylori surface glyeoprot 'PIb-IX or GPUb-Ia (or both). Some patients have ‘complete. ren ruultiple antibodies ogsinst different epitopes on the saine glycoprotein, whereas others have antibodies against one or more of the glycoproteins. hiteces! ly drug specific and do not cross-react wi rosponse after bbe made about progresses with mucocutaneous bleeding (orat vy menstrual bleeding), ecclymoses and petechiae neoanligen on platelet Factor 4 (PEA) of heparin. Antibody binding to PF4-keparin binds to the ‘membrane FeyRI receptor, thereby let activation, ombocytopenia, HIT is not associated with increased risk of thrombosis, NONIMMUNE THROMBOCYTOPENIAS icroangiopathic hemolytic anemia. This hrombocytopenie purpura (TTP) and hemoly' as well as syndromes com after lysis ofthe tra Jason and forms ian bind to autotogous platelet the platelt-s alloantigen reteased on plitelet lysis binds 1 platelets, which are then destroyed by alloantibody; it the patient's platelets is produced in ine complexes in many patient sequired TTP but aS yet undefined factors must be involved in otter patente HS is a syndrome characterized by hemolytic anemia, duced Immune Thrombocytopenia ‘of drugs thal cause finmune thrombocytopenia is extremely large, but most cases are caused by eight drugs: quinidine, quinine, gold salt, sulfonsinides, sid rifampicin. In rece antagonists (abciximab, usually veces subse caused by E coll. This organism elaborates endothelial celts, which initiates pls individuals often present with bloody by BUS, Familiat EUS accounts for 5 to 10 Mm 16alt Paujabow 19 Kienpose poo Jo ssauyea w Aq pasnes ae temdand ay yusax Souapuay Fu}poa1q se poyesoya ae pe sen json KwoIMsy S9BeyOUIDY JeSCOM Due 1¢ palwposse scyHeunouge F8/ROER A : oype jeuoue mous soya any “emdund &q 29 ‘aajssecer joM0=9}m siozpusg s2nnog-pxeming SuaCHOSIG CARTAN svunainduvinosva tes; SuaCOSIG IATALV Id AALLVLITVND TES Jeactibe pus nowsaupe anja swexqoiljn uo pastaboe 0} amp 19094 50 36H Msi snoqanoayy posta ue iplor poyelaasse us9q JOU Seq UorpEWUKEY|OL OO: 20 ajrioe oF stueddsar uy siso}Coquiosuy, “seg0ud anrqesatyosdoyacen BU ‘onjsoonta aig: 20 "Ado uousypar “sBnup yo ynsas v se woyssasd ‘enued 10998) 39 jo eoneaq Baypestq 40) YSU URW B AM saNEy FAL MLN In Be) saps0ss sxajdwoo Atyegoat a st net poajonu surxoy ayfaads LL Bp: paisaypaeae ra fo ou ayr puE ‘poUty2p ABoqO uo9q nqujoya kan "Seapuosip aansseiroadoyiusl, ‘soni 3H0q — sour uy NOUSAGONa JSTALY 1d CASVRIAT AG GASMYD SVINAdOLADOGNORHL t Buipssig UL “saMHes tees thy SUadUOSTE EBALA09V ea ney Stuaee uoes2<880 day Jo 2683[21 poonpas “owospicis 5 ea yous usayds a8 2 seypag cusp fo fue app 1 Soup_yEU ood seINS, now st aMODUKS roFaIELE Aes) epduuoe opr -ginag 220p moo poljesuosta 6 spea] wend "4 to}sey acomajdiion jo taa9p joutoage te 10 Aouotoyap WARE O} FAO LG 2A i ay fo worsseurs ouoyorufip 40 zou9599 a, Jo seeE705 SBpREP RIN oa PasayHemostasis dcorders Hemostasis disorders Hemostasis disorders Hiss tizordecs for less commonly, thrombocytopre late, Haemophil oon the face, lips, nar is the most comunon sy:nptom less upper or lower Gi bleeding (50%) snd hem in the lung may ses unprovoked of, raore rauma. Moderate and laboratory screening assays, activated partiat dirombopl evaluate the cause of abnor ‘emorthagic events sesult in Life morbidity of coapulopathies can or syareness and prophylactic replaceinent of the defi uiput heart failure to paradoxical or septic les several disorders chaructarized by 1d vessels. The most coninon, Fa gene encading lefictency of | Jeeding fi A, caused by a deficiency of clotting B, caused by a deficiency of fact tary Hemophilias iris sexlinked recessive disorders of hemophilia A and 8 are estimated to ‘approximstely 1 of every 5000 and 1 of every 30, ‘The higher incidence of hemophilia A may be duc to the greater ‘purpura can also be venules, but can be al endothelial cals,ext i roajap 2k, usted Sag APU pee ssenuosydeu lem posyuos og Kou yseyse ‘ayes jouer aonpord nowpre “Y eanPleus © HE Shop poog eimain no pein aie uonsayur pue souois jeas1 aye woIsNjaxe vonuIMA wasn we si (KpUnUUON) NZ addy, 0 FAB So sysondetp a 5} eygydousy 0 aepuoass iven Aaauynoruad aq oF B04 ‘dgterepnasd adie sjorepd pasezisap 5} yueLes 29) Envaumuods “sosoxpreuny Jo wounsau ap 205 (SCIYEN) SBup AoreWor tu Bios 9f04n | “hue cepimisuon zo 2sn sup £4 40 voisuouadKiy (aod pu sisouss!9 oy Krepuos2$ pussayard sy 40 anuita at pe Snisszar 0. huouucep Ee ued put “gous Wa 1 pay ouated Gage Jo woe Msiuiouide spmmurqs cadky 0 28 Sy pi Bye4nye sexo 3 sings arta a yp tnd {¢ajep stent apo poop oe oped even oud ayy JO wo pus marae arma 2 pay oem ‘ofl ant Snnebooo ys Jo vonmoyleers autcatl su, 5 yma asad pur sit ave sued suo8szamoy souoinopaud cya op £0 {Jo anata yin oes Gog eae aye Sige wou bout ou, areal etesgenigg wos Asenpesa aSVasia SaNVUOIT IA SOA uog oF SMeurep yemuaro nse sp22qg powwow 40 saosuTD2y “oan 420 exanesy uprn sBepiowsy ssayord £9 pus senseq Yor pus (Sso.KpsoMey) BEAD! by suena Biypozyy snosusjuods waukass £4 pazuaiesey> 51 aseasIp asoKos suorotap a8 4g posne 5} A243 32080 9 suisdouoy 2xonos pe “stoaip szou up suonnus XT 40)D8) IsEHUOD L500 fue suoneurer quod qium paseioorre ame uoeq svanep stag) 30 $24 Pue “SUOS Ha JO J124 04 JopsDsIp vaneyABECD ain yuisuen siouie apeueg “sain sodygo aud09q suaKyBAOP HexD 10g “Suos usp 6) 2898 st IHREN ION 9p attosoRBAD x {HUE aK) TD Suriaajap eps sebegy =tinsomesys 3c 0 te BHo| DO PSHE =I] 1A so} 104 sun a ‘Saseastp OSS PAYOIL- NES KIO BIN SY {sued aseg 900'r8) sue 9 10s 24 Ln 19 op 8 BOPEIAAL 9} RE ‘nse Aeut stoyap fanjonyoiuy pu Ssipiostp una, “swok aod yz ApjeuuNoudde =| -aBeyiouay Jo se0e of (rie) 208 BOE 1900 PONG peHUOUID.ALY voui9y 28015 so aposide 2up Neat ye saumLE Jour Jo qusoisd GauIey -sIuD%e ansjouqysUe 30 ssn ays Sq p=tes0s POS orc SapIOS HSRROUTT ropes 2 (syed 2859 999°981) 2298 ap Ra,Homostesis disorders multimeric. perspectives but lacks an intact binding site for factor VIII, Unbourd factor VII is cleared from the cireulation that occurs In 1 of every 1 uals. It is characterized by almost complete absence of FACTOR Xf DEFICIENCY (HEMOPHILIA C) Pastor X1 de ly an autosomal recessive ti ion pattern. The clini Iendencies in factor XI deficiency are less severe than those observed luemophilia A or B and ate not CONTACT ACTIVATION FACTORS Although factor XI is important for activating Factor (X in the intrinsic jn any of the other thrce factors {factor igh-mwoleculas-weight Kininogen) produce in vitro Inboratory abnormalities. Patents have no clinical Bleeding. PIBRIN-STABILIZING FACTOR) DEFICIENCY is a transglutaminase that is activated by thrombin end ross-Links fibrin to protect it from lysis by plasmin, 1¢ also Is wg and issue repait ond seems to be crucial for ing a viable pregoancy. Delayed bleeding alter surgery end hallmark of the disease: however, easy bruise defective scar formation and dehiscence, and ‘Spontaneous abortions are increased in severely affected women. DYSFIBRINOGENEMIA AND AFIBRINOGENENTIA release of Je A), and. 20% predispose individuals to thrombophilia (usually ed by impaired Morinolysis). Concurrent bleeding. sod thrombosis also DEFICIENCY OF FACTOR V (PROACCELERIN, LABILE FACTOR), Factor V is @ component of the prothrombinase complex that esserables factors ‘Va and Xa on the phospholipid membrane of the platelet for prothrombin (Factor 1) activation to thrombin, Iss deficiency may be caused by: ba Hemostasis disoucers = Congenitel Fector V Deficiency Acauited Factor V Deficiency ~ Combined Deficiencies of Factors V and VI. DEFICIENCIES OF VITAMIN K-DEPENDENT COAGULATION (DEFICIENCIES OF FACTORS I, VU, AND X) Congenital deficiencies of factors Il, Vi, and X are rare, eu inherited. disocdes Heterozygotes (with factor levels approximately. 20% cr ¥ asymptomatic except in the immediate newborn pe: ‘eney exacerbates. the undedi ficiency. Acquired factor VII deficiency Johnson and Gilbert syndromes, FACTOR X DEFICIENCY IN AMYLOIDOSIS Actuired severe deficiency of factor X, offen accompanied by deficiencies of ther vitamin K-dependent factors, occasionally occurs i, aulvide loidesis, because amyloid Gbrils in the reticuloead. bind endogenous and exogenous sources of factor X COAGULOPATHIES SECONDARY TO ANTICOAGULATION coagulopathies are secondary 10 ‘and other coumarin apalogues and to 1 n (DIC}, also refesved 19 as consumy caused by a wide variety of serious disorders process dominates the clin ancy, envenomati ion of the disordar. TRE RE Se MMOR CAUSES OF DISSEMINATED INTRAVASCULAR COAGULATION Wntetions ~ Grain-netve str sepss Othe bacteria, fang, vests, Rocky Mount spottes fever a 2. Immunologic reactions: a fee ee ne = Tranapnt ees 3. Obserc complications uid embolism ed dens faus Abrpto placentae “Tore preeclampsia = Septic boron 4. Matigamies E 15volouugy Yoram) spuBNAayIEa HOA THEA XLTX IA SODEE le YOLZOTD wIAOsITONd) wquOMOLy — (u9pie"F a Jorg) f2oueysiss4 2 wysioud patanciaa) By A0;o0q — suojouy sHoqtuostpoad pases34) “7 foapusp g wooly founoyep 9 fonsiousp (uD sso eye SALVIS TGV IND WOOAIAH AUVATYA TY'S poor louge ‘meg pooig Jo seoueaarssip 1p MoquON) parraboy -sussiEEyooUN Borseynfau “xaxduwwo Aq sisoquecsy) o1 sWoRed Se0sypote! 3 Stpioap pauinbae Xysout “estoalp 218 SOMME a1Geinse09 9M ky LaepwHosas 34, siaraiid jo uomenae ‘soul JO WNSAH B Se sn290 Wed sISOQUONEN aAoJOMe “KyOIRAIES <7 “Aoraty apioquiosmpaud w 30 [949] poseoiom tosey apoquioayinne 2ABojo}s4yd ¥ 30 KouoryeD — ‘aoa S:0pI0SIp asap Jo ORL neo aie sa49ye a1 ‘AAUDe 124} Oy 3ouRIsSAL 20 aza;eF wuElOseoD| 8 yo sowonbesuos © Syensn st sysoquuoNyt OF Mm Jeuns0u jo fano4 poonp sodsipasd peywazu0) 24 98'e| Jo sysoquuaay 03 osodsipesd siowumy juste uw “urasés yrtod 249 ay sisoquioiy 04 ssbaderpoud wion esuven.fasjou Ramo} Jo sisoquiosy ues doap op sosadsipoxd oan ip seys. nouns ousye ‘iquiosy) (eHoue Jo uoNeUE] ay ) sosodsipod etsosmpasolsuye aylalesS 204 3OFDR} a9 Leip B1OMY Jo SAAS a4 OF on HIED] fase. saadPIsU! jsoU UL “sisoquion 10) 48110 Kouopua} aoa ‘stjoud uoyuea aypaKls dh sopyjeatiouge pannbs 0 dnor8 v 5 ‘seymmdoqmony x0 s2ye}8 a1qe|nSeO9:00<4 34, 21804 50 pa od @ asnea NOLLVOIAISS 19 GNY NOLLINIIIA "UPS StHAAOSLA DLLODWOURL FS Prout pus syuLeUspoatoy sfuIEAS cq pauedineDse 1 OF pea puE susz0 atvos oF Addis Pools EEE EE eee cea Ore eee ee ees Sepa TROUT sqususBuesop 2) set ‘ay ospetoxduos uso O4Q ut sIsoquOstp Jeyn2seAO494.A ICL! TeostUA st RENE AuAjOUDH UH easmoy ‘SxEauis poo|g U1 saxSoySIY>S Jo aouBzDedde 24} 0} P22) ‘poo{g por Jo Non RAUB aeres oe uoRsOKap ULsqy Je{NOSEREAL “SICL fusjod ame Sacld “(Gada) Sioxpoid uoaperdap. (380) poe) mq wS0Rip oy waNse|d ajeiauad sxopeasto® uSBourmse Aampuosss Jo se20014 819 SSEIOUDS DIG v} woNEWAE; FSA paseas WL vuayy agvelae 0) serisoKieyeaur saareur Sucq Jo Ayoudeo oy! JO SONS U) safstetd pie “ate aaysoquuss 0} sant] 241 Jo Sysedea amp yo ssaaxe ut vanse ur gon ) apiaord (uoyruoussuD uy su wow) unyp s2yy0 saseaj0rd pi y2ko 8 a) sopaRf ans wn fay Jo Squsuoduio3 “= {Jo soquuns 24 uo Wosssa1d39 10 a, pooyg 21 ssa028 sue so}; we As s088iN you) sovusqsqus juojndeosaal yo womeinon9 aL OY LUD st a5;ED Jo ssoypIETar “KBojoisKudowed 9}5eq aL srounyseyeosen — uuscanoue oy — \ospUAs REDDY yoBqESEy|) BUIOIBUBUE JUDIE, — suDpIOSTD 2e|MOEA “3 | koimg — suuioqoa, mod] — wisyoqua yey = sagiodsyy = stung — ar ysuy Aantal urergy = ‘sonia ane sworpuds ssansip Gowards>y) uoqeuouaaus sppporoded ano equana} sopektwod ausy seuDwjasouepy — muoursies apeoraueg Sepia TRYHemostasis disorders binding to CBP may cause: tendency for throm! ied protein C (APC), loss of regul nd Van C Resistance (Factor V Most subjects with functional activated have a single, specific point nvutai factor V is resistant 10 rary Hypereoagulnble States tor VIII coagulant activily are a significant risk factor hrombosis. ieressed levels of factors Vil, IX, and XI fact 128 Hemostasis disorders and certain dysfibrinogenemias) thet cause a thrombotic rather than a bleed! dithesis. 5.43. SECONDARY HYPERCOAGULABLE STATES SECONDARY HYPERCOAGULABLE STATES L000 FLOW BLOOD composimon | vessrt wath apuorsiaLinies _ | ABHORMaLITiES ABHOREAALITIES TWPERNISCOsITY ies of hemostasis are involved in the hypercongulable state process of chronie DIC. The rs, such as immobility, indwe catheters, or a butky tuunor mass compressing vesscls, ing central venous 29 8vet te ‘Srowesuadive yy al, “§ suequsBta ety auamjoa peng Kay ye sonssn 0} wo98Kxo 40 952940 19 Lavo wtgaydoaiay TTT RT WF piduogdeoyd squowe op pu 18H) yin polejacase s{ ausospmds a4), SH Alita B pHe “epuadorGaoquiosyp “Seay Jo wnos 2ynjasqe ‘Aq p90 51 SM J Kuoedeo Bayareo-waB.xo stp aa. ue ig I re IE SvIWaNY 19 Suaaaosid 17149 Goold aay 9 WLAVHO SAT AS TOT TT pL SO‘Red blood calls dieorders Ret ood cats disorders poxie is caused by a decreased amblent oxygen concenteatio ivery of oxygen through the hungs and to hemoglobin molecules shunting of blood, hemoglobin mutants id decreased abi ‘Compensation reflexes Increased anaerobic retabotism Incrensed hemoglobin Aissociation Figure 19: Hypoxia compensatory mechanisms 12 sere ‘Red blood ceils disorders io cia inorder skin and inucous ~ depending on the type ofa a "y x © Yellow =i become cracked Cardiac effects | Anemia Increased reticulocyte count Hepatic effects (fatty change, necrosis) Patton Hb<7-8mg/at Lethargy a | Figure 20: Pathoptogical effects of hypoxia. An increasing su is not only modulated by tuediators Including system, norepinephrine 13Goons i poapocha *p sSaup jeiqomwaice ue ansssauddasouninns swos pus skup ornadesainc ko0.H) 9439 prose SniGous10U) Kourresip (ogg) wnparodoryriuz t WANOM Xf SALADOURL NAA 20 NOLLONGONA CALAN AV SVIWANY AO NOLLVOLUISSV 19 SIO LOISAHA OLY MOINIVIN INOS AS SALAQOWHLAWA JO NOLLDTLGOwd GERULVAN AW GASAVO SYBYANY TE9 SEPP SSS HOUTA PA, sousasouss jenjen jo e7e! op ypeaneay Oa 39} auonuoi{ aorepes Suyeuaious fq apeod: woo, 0} puodsar “Aoupoy oq JO 8 F aqt ge dis op 4 payeay 29 0) IY she acl Serene We Sey SuoHIpUOD JeauoU sopun erdoon 4:9 BuRed blgod cells disorders 9 Talasseuiag © The prototype for impaired EPO produ severe BPO deficiency after OF EPO, gener 10% of normal, are produced ‘of EPO produced by pationts after neplirectommy is derived sufficient to generate only a si ry patients who tk hemoglobin autoantibodies against EPO have extremely tow to ‘culating BPO levels and severe nneinia ted with inappropriately low levels of EPO for the degree NETIC STEM CELLS IROID PROGENITOR CELLS sd by a deficiency of hematopol Is also results in anemia, Ey 136 if BPO eis soos aeiestsisascse se Red blood orders production is appropriately increased forthe degree of anemia, {arget marrow precursor cells are deficient in number. In almost iphenicol or gold sal infections ding anorexia nervosa, hypoplasia, / thrombocyiepania which may causes bleeding, 2.4 bone marrow: empty bone marrow ia, recurrent infections selated 10 leikops ‘or bleeding due to thrombocytopenia. MYELOPHTHISIC ANEMIA is caused by ini normal marrow space by abnormal of non ‘normal or elevated, Causes of myelophtisic tisorders,, i cells. The EPO level is ia: myelofibrosis, lipid storage ow. Symptoms of anemia and of ‘extramedullary hemopoiesis (myeloid met PURE RED CELL APLASIA Preeursors. The BPO level is norm aplasia: © Acute aplasia: may be induced by viral infection aoeet yodstl uoK0 uses pue snos0 sadlucys Kypeuocied sooes 29496 Hf eseesed ouseds 0) ssosiloud feu asvesip sui "uonugla yo esuas = pus “uoudaroLdord Je SHUM “es jeuuOUGe apoypu. sMOMULKS esaLL “UeR 2avy swuoned 30 %py AjIEMIKGIddY “LpDLOVE ~ sweojaCur semoNETY “PisaKpsaaEd — Gaysdosnsudjad) amospuds yworZojoamau asneo was sessso0Nd eapeaIotop souaege at HRMTENS ok a) | ]OL NOMA ek CIE CHEMI ssnoeffou ‘ouoye egy Jo 2609 oq UL So sisatodo}mudy sapoesfeus pOiE9 st siyso oumodoreusay jo uouesnyew ify o10yaq siosmo017 Jo uBap 24L LUNs palhgwso% O1eUE 2u0q JeYNI}DOIOdKEE “ywauicoppaap sanUIE;Ip 40q Iba uOREA] YOu 22 moan 9u0q Aiojesusduo> esne> uonipyo> sy -pOO|G OIL paResfas uv soLCoojnues ssuuanos pur sayKsosypirs simyens 30 sinqun p node Ay Stiueuuopaid “siosanaaid apetodoyenes) yo RIe3p is04 “s>NUNTLD sISSURUAE YN pur ‘psonpas st siseyiuds SEZ utes aan. sisaiodonyydi Suunp umop panos sf af2 VINGL Sur '=DU2EGE BL “SsayIUSS YRNCL UF JOE VINNY SLISVTHOTYDEN 40 SISANZOOFLYS Faoodajeway paseasout *Soue ‘KouvuBad :syaomaayaboa paseesout (4 EAP PORTAL a FELT TT “unadospaugn “soap parelsieesits 10 sepruevoy © pro qitin suaprons] ein SUD pus SapLosp yeuusersd ascysIp o2 NP 2°. 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Decreased cell proliferation in the body Megaloblastic “Low myelin form Figure 21: Pernicious anemia pathophysiology ‘Therefore desiciency of folic acid produce defective DNA synthesis too. 140 san secs ye ra Red blood cells disorders 6.1.14. IMPAIRED HEMOGLOBIN SYNTHESIS: DISORDERS CHARACTERIZED BY DIMINISHED HEME SYNTHESIS huicroeyti TRON DEFICIENCY ANEMIA is usually multifactorial, asd cause ineffective erythropo: ‘Causes of tron del low dietary ‘e225, nuls, legumes, beats) low gastric processing (gastrectomy) low intestinal absorption take (meat, low iron storing (intestinal epithelium, liver, macrophages) + blood toss (pregnancy, intravascular hemolysis, meesnicaltreuma) ochromic ancinia shores the same reased depend on the extent of anemia, but in general the complains of symptoms related to: Hypoxemia, Thes dyspnes irome). Dyspe} atrophy of the gasirie mucosa, n deficiency . syndrome, Sore: patieats develop {0 cat icc, paint, or dirt (geophagia). Thes syndrome, such a8 an urge forthe pica