USMLE Step 1 Web Prep Cellular Injury and Adaptation

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BIG PICTURE
Cellular injury o Reversible injury o Adaptation o Irreversible injury + cell deat
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CAUSES OF CELLULAR INJURY

Hypoxia "ost co##on cause o$ injury %e$inition o &ac' o$ o(y)en inability to synt esi*e A+, by anaerobic o(idation

&oss o$ A+, o -ailure o$ sodiu#.potassiu# pu#p o Increased )lycolysis o -ailure to produce proteins "ajor causes o Isc e#ia o Cardiopul#onary $ailure o %ecreased o(y)en carryin) capacity
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CAUSES OF CELLULAR INJURY CON T

In$ections 0acteria1 viruses1 $un)i I##unolo)ic reactions 2ypersensitivity reactions Autoi##une diseases Con)enital disorders Inborn errors o$ #etabolis#
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CAUSES OF CELLULAR INJURY CON T

C e#ical injury %ru)s

,oisons 3ccupational e(posure &i$estyle c oices

, ysical $or#s o$ injury +rau#a 0urns Radiation

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CAUSES OF CELLULAR INJURY CON T

5utritional or vita#in i#balance Inade6uate calorie7 protein inta'e o 89as ior'or. selective protein de$iciency o "aras#us. total calorie de$iciency :ita#in de$iciency o :it % ric'ets + osteo#alacia o :it 8 coa)ulopat y o :it 012 #e)aloblastic ane#ia o -olate #e)aloblastic ane#ia + neural tube de$ects
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CELLULAR CHANGES DURING INJURY

;eneral Adaptation Reversible injury Irreversible injury + cell deat Cellular response dependent on +ype %uration <everity +ype o$ cell "etabolic state
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CELLULAR CHANGES DURING INJURY CON T

Critical intracellular susceptible syste#s %5A ,roduction o$ A+, Cell #e#branes ,rotein synt esis "ec anis#s o$ cell injury 3(y)en.derived $ree radicals o <upero(ide1 ydro(yl + ydro)en pero(ide A+, depletion

Increased cell #e#brane per#eability In$lu( o$ calciu# "itoc ondrial dys$unction

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RE&ERSIBLE AND IRRE&ERSIBLE CELL INJURY

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IRRE&ERSIBLE CELL INJURY

<evere #e#brane da#a)e "yocardial injury troponin 1 C8."0 + &%2 2epatitis transa#inases ,ancreatitis a#ylase + lipase 0iliary +ract obstruction al'aline p osp atase "ar'ed #itoc ondrial dys$unction <9ellin) %ensities in #atri( ",+ Inability to produce A+,
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IRRE&ERSIBLE CELL INJURY CON T

Rupture o$ lysoso#es Autolysis 5uclear c an)es ,y'nosis 8aryorr e(is

8aryolysis
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CELL DEATH
(o)p*o+o,i- .yp/0 of 1/-)o0i0 Coa)ulative necrosis "ost co##on %enaturin) + coa)ulation o$ proteins > <lide i#a)e o$ eart ?cross section@ ,ale1 yello9 in$arction
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C/++ D/a.*
Coa)ulative necrosis > <lide i#a)e o$ eart ?#icro@ &ac' o$ nuclei &i6ue$action necrosis %estruction by ydrolytic en*y#es 0rain1 pancreas +abscess
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(ORPHOLOGIC TYPES OF NECROSIS CON T

Caseous necrosis Coa)ulative + li6ue$action necrosis ;ross. Acotta)e. c eese.li'eB o ;iant cells o Cpit eliod cells o &y#p ocytes +0 -at necrosis Action o$ lipases on $atty tissues

0reast1 abdo#en + pancreas

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(ORPHOLOGIC TYPES OF NECROSIS CON T

-ibrinoid necrosis > <lide i#a)e o$ 'idney ;lo#erulus. a$$erent arteriole. pin'. $ibrinoid necrosis Arteridities %ead tissue

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(ORPHOLOGIC TYPES OF NECROSIS CON2T

;an)renous necrosis %ead tissue %ry )an)rene . blac' toes . coa)ulative necrosis Det )an)rene . yello9 areas . li6ue$active necrosis

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APOPTOSIS
%e$inition ,ro)ra##ed cell deat Active process "orp olo)ic appearance Cell s rin's 5uclear c ro#atin condenses Cytoplas#ic blebs Apoptotic bodies , a)ocytosis &ac' o$ in$la##atory response
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APOPTOSIS CON T
<ti#ulus $or apoptosis Cell injury + da#a)e &ac' o$ or#ones1 cyto'ines + )ro9t $actors Receptor. li)and si)nals -as li)and +5-

Apoptosis is re)ulated by )enes bcl.2 o In ibits apoptosis o ,revents release o$ cytoc ro#e c o 0inds Apa$.1 p.53 o <ti#ulates apoptosis
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APOPTOSIS CON T
, ysiolo)ic e(a#ples o$ apoptosis C#bryo)enesis 2or#one dependent + y#us ,at olo)ical e(a#ples :iral diseases E epatitis ?Council#an body@ ;ra$t vsF ost Cystic $ibrosis
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ADAPTATION
;eneral Result o$ persistent injury ,otentially irreversible "ay neoplasia
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ADAPTATION CON T A.)op*y

%e$inition %ecrease cell si*e Causes %ecreased 9or'load Isc e#ia &ac' o$ or#onal or neural sti#ulation "alnutrition A)in) "icro

<#all s run'en cells %ecreased intracellular co#ponents +

C"

autop a)oso#es
o
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Atrop ic 'idney due to arterial occlusion

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HYPERTROPHY
%e$inition Increase in cell si*e + $unction Causes Increased de#and o , ysiolo)ic o ,at olo)ic

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&e$t ventricular concentric ypertrop y. ypertension

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HYPERPLASIA
%e$inition Increase G o$ cells , ysiolo)ic causes Co#pensatory ,at olo)ic causes Cndo#etrial yperplasia ,rostatic yperplasia o$ a)in)
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(ETAPLASIA
%e$inition C an)e o$ cell type to anot er C(a#ple 0ronc ial epit eliu# . colu#nar epit eliu#
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s6ua#ous #etaplasia
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DYSPLASIA
%e$inition Abnor#al proli$eration o$ cells Increased 5:C ratio &oss o$ polarity C(a#ple Cervical dysplasia
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cancer
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OTHER CELLULAR ALTERATIONS DURING INJURY

Intracellular accu#ulations &ipids ,roteins ;lyco)en stora)e diseases Cndo)enous pi)#ents o &ipo$uscin.i#a)e "elanin
o
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2e#osiderin
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OTHER CELLULAR ALTERATIONS DURING INJURY CON T

2yaline c an)es %e$inition o ,in' o#o)enous appearance Intracellular yaline o "ultiple #yelo#a o Russell bodies C(tracellular yaline o Absence o$ linin) cells
o
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,in' yaline #e#branes. 2yaline #e#brane disease o$ ne9born

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PATHOLOGIC FOR(S OF CALCIFICATION

%ystrop ic calci$ication vsF "etastatic calci$ication %ystrop ic calci$ications Calci$ication in dyin) 7necrotic tissue "etastatic Calci$ications Calci$ication in ypercalce#ia
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PATHOLOGIC FOR(S OF CALCIFICATION CON T

%ystrop ic calci$ication C(a#ples o -at necrosis o +u#ors. ,sa##o#a bodies
o
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At erosclerotic pla6ues. i#a)e

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PATHOLOGIC FOR(S OF CALCIFICATION CON T

"etastatic calci$ication %e$inition o 2ypercalce#ia C(a#ples o 2yperparat yroidis# o ,arat yroid adeno#as o Renal $ailure o :it % into( o "il'.al'ali syndro#e o "etastatic cancer to bone