47 High Yield Recall

8/10/2019 47 High Yield Recall

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ANATOMY

Ø Dr ai nage pat t er n to t he super f i ci al and deep i ngui nal l ymph nodes.- Anyt hi ng f romt he i nt ernal geni t al i a ( t esti c l es, ovari es, ut erus)dr ai ns t o t he para- aor t i c l ymph nodes- But what dr ai ns i nt o the super f i ci al and deep i ngui nal l ymph nodes?- Deep i ngui nal l ymph nodes drai n the l ower l i mb, whi l e super f i ci alnodes dr ai n t he ext er nal geni t al i a and super f i ci al t i ssues. Thi s i s whywe never r esect or even bi opsy vi a a t r anscr otal appr oach despi t e t hef act t hat t he t esti c l es drai n i nt o t he para- aor t i cs.

Ø HY TI PS- 1. Di r ect her ni a: l eaves abdomi nal cavi t y medi al t o i nf er i orepi gast r i c vessel sI ndi r ect her ni a: l eaves abdomi nal cavi t y l at er al t o i nf er i or epi gast r i cvessel sFemoral her ni a: pr ot r usi on of abdomi nal vi scera t hr ough f emoral r i ngi nt o f emoral canalLumbar punct ur e: needl e i nt o l umbar ci st ern bet ween spi nous pr ocesses

L3/ L4 or L4/ L5 Per i car di ocent esi s: wi de bor e needl e i nser t ed t hr ough5t h or 6t h i nt er cost al space near st er num. Caref ul not t o punct ur ei nt er nal t hor aci c ar t er y- 2. Thyr oi d C5 Duodenum T12- L1St ernal not ch T2 Ki dneys T12- L3Bi f ur cat i on of t r achea T4- T5 Conus medul ari s L1- L2 adul t , L3 newbornHear t : Base T6- T9 Umbi l i cus L4Apex 5t h l ef t i nt er cost al space- 3. Knee: 1. Pat el l ar l i gament - damage t o f emoral ner ve or spi nal cor dL2- L4. Loss of pat el l ar r ef l ex 2. MCL- t ear al so t ears medi al meni scus.Passi ve abduct i on of extended l eg at knee j oi nt . 3. LCL- passi veadduct i on of extended l eg at knee j oi nt . 4. ACL- ant er i or dr awer si gn.5. PCL- post er i or dr awer si gn. 6. Ter r i bl e t r i ad- MCL, medi al meni scusand ACL t ear s.- Hi p: 1. Post er i or di sl ocat i on- head of f emur moves post er i or t o t hei l i of emor al l i gament . Pr esent s wi t h l ower l i mb t hat i s f l exed at hi p

j oi nt , adduct ed, medi al r ot at ed and shor t er t han opposi t e l i mb. 2.Fract ur e of neck of f emur pr esent s l at er al l y rot at ed and shor t ened.- Shoul der : 1. Di sl ocat i on- may be ant er i or or post er i or . I f ant er i ort hen axi l l ary ner ve may be damaged. 2. Separat i on- r esul t s i n adownward di spl acement of cl avi cl e.- Cl avi cl e: 1. Fractur e- most common at medi al 1/ 3. Resul t s i n upwarddi spl acement of pr oxi mal f r aagment and downward di spl acement of di st alf r agment- 4. Br achi al Pl exus: 1. Axi l l ar y n- di sl ocat i on of shoul der , abducti on( del t oi d) and l at er al r ot at i on ( t er es mi nor ) ar e compr omi sed. 2. Longt hor aci c n- wi ngi ng of scapul a ( ser r at us ant er i or ) . 3. Radi al n- wr i st

drop ( ext ensor s of f orear m) . 4. Medi an n- ape hand ( t humb muscl es) andf l exor s of f or ear m i f damage i s at el bow or above. 5. Ul nar n- cl awhand and r adi al devi at i on of hand, l oss of some f l exor s i f at el bow orabove.- 5. Per i pher al ner ves: 1. Common per oneal n- f oot dr op ( t i bi al i sant eri or m) and i nver si on ( per oneus muscl es) . 2. Deep per oneal n.ent r apment - Compressi on of ant er i or compar t ment muscl es of t he l owerl eg by ski boot or at hl et i c shoes t hat ar e t oo t i ght . Causes pai n i nt he dor sum of t he f oot t hat r adi ates t o the space bet ween t he f i r st t wot oes.

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ner ve f i ber s f r omt hi s t r unk run i n t he medi an and ul nar ner ve andsuppl y al l t he smal l muscl es of t he hand ( l umbr i cal s and i nt er ossei ) .Par al ysi s of t hese i nt r i nsi c muscl es of t he hand causes t he f i nger s t oassume t he "cl aw hand" posi t i on demonst r ated bel ow. Thi s posi t i on i scaused by the unopposed act i on of t he ext ensor di gi t orum ( whi ch ext endst he met acar pophal angeal j oi nt s) and t he f l exor di gi t or um super f i ci al i sand pr of undus ( whi ch f l ex the f i nger s) . Normal l y, t hese muscl es ar eopposed by t he l umbri cal s and t he i nt erosseus muscl es.§ Lect ur e Notes

3. Wr i st Dr opWr i st dr op i s caused by i nj ur y to t he post er i or cor d and t he r adi alner ve i n t he axi l l a. Thi s i nj ur y can be caused by i l l - f i t t i ng crut chesor a downward di sl ocat i on of t he humer us. Di sr upt i on of t he r adi alner ve r esul t s i n paral ysi s of t he t r i ceps, anconeus, and extensormuscl es of t he wr i st . The person wi l l be unabl e to extend the el bow,wr i st , or di gi t s. The r esul t i ng posi t i on of t he upper l i mb,demonst r ated i n t he di agr am bel ow, i s cal l ed wr i st dr op.§ Bi g Snel l , pg 484

4. Medi an Nerve Pal syI nj ur y t o t he medi an nerve wi t hi n the el bow r egi on r esul t s i n somechar act er i st i c def i ci enci es ( whi ch you shoul d be abl e t o pr edi ct byunder st andi ng the di st r i but i on of t he ner ve) . The ar m muscl es are notaf f ected because none of t hemare suppl i ed by t he medi an. However,pr onat i on of t he f orear m, f l exi on of t he wr i st and di gi t s, and movementof t he thumb are sever el y af f ect ed. The pr onator muscl es of t he f orear mand t he l ong f l exor s of t he wr i st and f i nger s wi l l be par al yzed, exceptf or t he f l exor car pi ul nar i s and medi al hal f of t he f l exor di gi t or umpr of undus. When t he pat i ent t r i es t o make a f i st , as shown bel ow, t hei ndex and to a l esser extent mi ddl e f i nger s r emai n st r ai ght , whi l e ther i ng and l i t t l e f i nger f l ex.§ Bi g Snel l , pg 486

5. Axi l l ar y ner ve i nj ur y The axi l l ar y nerve may be i nj ured by f r act ure of t he humer us ordi sl ocat i on of t he shoul der . Fol l owi ng sever ance of t he axi l l ar y ner ve,t he del t oi d muscl e i s par al yzed and at r ophi es.6. Ul nar ner ve pal sy

The ul nar nerve can be damaged when t he medi al epi condyl e of t hehumerus i s damaged ( l i ke when you hi t your f unny bone) . Ul nar ner vedamage l eads t o par al ysi s of t he f l exor car pi ul nar i s, medi al hal f oft he f l exor di gi t or um pr of undus, and al l of t he smal l muscl es of t hehand except f or t he thenar muscl es and t he f i r st t wo l umbr i cal s. Wi t hpar al ysi s of t hese muscl es, a per son i s unabl e t o f l ex t he r i ng orl i t t l e f i nger , adduct or abduct t he di gi t s, or adduct t he thumb. Thehand assumes t he charact eri st i c posi t i on shown bel ow. The

metacar pophal angeal j oi nt s become hyperext ended due t o paral ysi s of t hel umbr i cal s and i nt er osseus muscl es, whi ch usual l y f l ex t hese j oi nt s.

The i nt er phal angeal j oi nt s ar e f l exed- al so due t o paral ysi s of t hel umbr i cal and i nt er osseus muscl es , whi ch usual l y extend the j oi nt s.

Thi s condi t i on i s most mar ked i n t he medi al t wo di gi t s. I n addi t i on,t her e wi l l be wast i ng of t he hypot henar emi nence and hol l owi ng bet weent he metacar pal bones due t o at r ophy of t he hypot henar and i nt erosseimuscl es.§ Bi g Snel l , pg 488

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6. Wi nged Scapul aWi nged scapul a r esul t s f r om i nj ur y t o t he l ong t hor aci c ner ve, asupr acl avi cul ar br anch ( C5- C7) of t he br achi al pl exus. Thi s ner ve t ot he ser r at us ant er i or l i es on t he medi al wal l of t he axi l l a. The ner vemay be i nj ur ed by a st ab wound, wei ght l i f t i ng, or a mast ectomy. Theparal yzed serr atus ant eri or can no l onger keep t he scapul a agai nst t hechest wal l , whi ch l eads t o t he wi nged posi t i on shown bel ow.§ Bi g Snel l , pg 481

KNOW THESE!! and al so know how t hey woul d l ook l i ke! ! !

ADDENDUM:Er b pal sy may r esul t i n phr eni c ner ve damage(C3- 5) .Kl umpke' s pal sy can cause Horner ' s syndrome, becuase t he sympat het i ci nner vat i on of t he f ace ar i ses f r om t he T1 r oot .Know t he dysf unct i on, t oo!Dysf unct i on of t he l ong t hor aci c ner ve l eads t o par al ysi s of t heserr atus ant er i or muscl e. Af f ect ed pat i ent s may not compl ai n of pai n,but t her e i s i mpai r ment i n the l ast 30 degr ees of over head armextensi on. The scapul ar r hyt hm al so i s di sr upt ed, and t he scapul a may

dr aw away f r om t he thor aci c cage; t hi s i s of t en r ef er r ed t o as wi ngi ngof t he scapul a [2] . To demonst r ate wi ngi ng, t he pat i ent pr esses t heout st r et ched arms agai nst a wal l ; t he i nvol ved scapul a pr oj ect s f r omt he t horax as vi ewed f r ombehi nd t he pat i ent ( UpToDate)

Ø > "Romberg si gn"?- 1. ask pat i ent t o stand wi t h f eet t oget her and CLOSE eyes- i f sway- - ->POSI TI VE ROMBERG! LESI ON I N DORSAL COLUMNS- 2. I f pat i ent sways wi t h eyes OPEN - - - > CEREBELLAR DAMAGE. .- I s i t because when you cl ose your eyes, you are t otal l y r el yi ng onpr opr i ocept i ve i nf o goi ng t hr ough t he cer ebel l um where as wi t h t he eyesopen, you ar e usi ng vi sual cl ues t o mai nt ai n bal ance

Ø 1. Ner ve i nvol ed when pt osi s + di l ated pupi l ? Al so2 . how wi l l t he eye l ook i n Horner s syndr ome?- CN I I I pal sy can cause pt osi s, down and out eye devi at i on, andsomet i mes a di l at ed pupi l and reduced accommodat i on.- Horner syndr ome i nvol ves t he t r i ad of pt osi s, mi osi s, and anhi dr osi s( l ack of sweat i ng due t o a l esi on of t he cer vi cal sympat het i c ner ve) .- Pt osi s wi t h di l at ed pupi l i s due t o CN 3. i t i nner vat es l avat er palsup, al so CN 3 i nnervat es, sphi nct er pupi l l ea ( NEAR RESPONSE) andci l i ar y- Al so, Lesi on of OPTI C NERVE:- I f you pl ace l i ght i n t he nor mal eye- - - >Bot h eyes const r i ct .- I f you pl ace l i ght i n t he af f ected eye - - - >Af f ected eye di l at es.- Lesi on of OCULOMOTOR NERVE:- I f you pl ace l i ght i n ei t her eye- - - >Nor mal eye const r i ces and af f ect ed

eye does not .

Ø Re: Pseudobul bar pal sy- Pseudobul bar pal sy r esul t s f r om t he degener at i on of cor t i cobul barpat hways t o V, VI I , X, XI and XI I crani al ner ve nucl ei wi t h spar i ng oft he I I I , I V and VI ner ve nucl ei .- Pseudobul bar pal sy i s a set of cl i ni cal si gns on exami nat i on, not adi agnosi s. The f eat ur es i ncl ude sl owed sl ur r ed speech, di f f i cul t y wi t hswal l owi ng, weakness of f ace, t ongue, and swal l owi ng muscl es, a

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t endency f or uncont r ol l abl e l aught er or cr yi ng, and br i sk j aw and gagrefl exes.- The most common causes of pseudobul bar pal sy are mul t i pl e bi l ateralst r okes, mul t i pl e scl er osi s, amyot r ophi c l at er al scl er osi s, pr ogr essi vesupr anucl ear pal sy, some f orms of st at i c and pr ogr essi ve chi l dhooddi seases.

Ø I MAGI NG TI PS ( HY) : TO BE CONFI DENT I N NEURORADI OLOGY , J UST GO TO YOUR MED SCHOOL/ HOSPI TALLI BRARY AND PI CK UP ANY 3 BOOKS I N RADI OLOGY WHI CH HAVE CT SCANS/ MRI .AT AN I NTERN LEVEL THEY DO NOT EXPECT YOU TO DI AGNOSE RARE CONDI TI ONS ,

YOU SHOULD KNOW THE COMMON CT/ MRI1) CT HEAD- - HAEMORRAGE - - SEEN AS WHI TE OPACI TY2) SUBDURAL - - SEEN AS CONVEX OPACI TY CAN BE OF SAME ATTENUATI ON ASTHATOF BRAI N BUT SHOULD BE I DENTI FI ABLE3) EXTRADURAL- - - CONVEX OPACI TY4) MENI NGI OMA- - DURA BASED BROAD MASS SMOOTH CONTOUR5) GLI OBLASTOMA- - - I RREGULAR MASS WI TH ENTENSI VE SURROUNDI NG EDEMA6) RI NG ENHANCI NG LESI ONS- - TUMORS/ ABSCESS/ I N AI DS PATI ENT I T I S

TOXOPLASMOSI S

7) SUBARCHNOI D- - - GOOD HI STORY PLUS BLOOD I N CI STERN THAT I S PROBABLY THE LI ST FOR CT HEAD. MOST LI KELY ASKED.MRI1) CORONAL VI EW- - PI TUI TARY TUMOR2) ARNOLD CHI ARI SYNDROME3) SYRI NGOBULBI A/ MYELI A- - - DI LATED CENTRAL CANAL4) SPI NAL CORD COMPRESSI ON

THESE ARE THE MOST COMMON ONESSTART LOOKI NG UP I N THE FI RST BOOK FOR THESE SCANS AND UNDERSTAND THEM.NOW LOOK I NTO THE SECOND BOOK AND TRY TO DI AGNOSE THEMSEE WHAT MI STAKES YOU MADE AND THEN GO THRU THE THI RD BOOK AND GI VE THEDI AGNOSE . I CAN ALMOST BET THAT YOU WI LL SCOREMOST OF THEM CORRECTLY.ASHDOC

TO BE CONFI DENT I N NEURORADI OLOGY , J UST GO TO YOUR MED SCHOOL/ HOSPI TALLI BRARY AND PI CK UP ANY 3 BOOKS I N RADI OLOGY WHI CH HAVE CT SCANS/ MRI .AT AN I NTERN LEVEL THEY DO NOT EXPECT YOU TO DI AGNOSE RARE CONDI TI ONS ,

YOU SHOULD KNOW THE COMMON CT/ MRI1) CT HEAD- - HAEMORRAGE - - SEEN AS WHI TE OPACI TY2) SUBDURAL - - SEEN AS CONVEX OPACI TY CAN BE OF SAME ATTENUATI ON ASTHATOF BRAI N BUT SHOULD BE I DENTI FI ABLE3) EXTRADURAL- - - CONVEX OPACI TY4) MENI NGI OMA- - DURA BASED BROAD MASS SMOOTH CONTOUR5) GLI OBLASTOMA- - - I RREGULAR MASS WI TH ENTENSI VE SURROUNDI NG EDEMA6) RI NG ENHANCI NG LESI ONS- - TUMORS/ ABSCESS/ I N AI DS PATI ENT I T I S

TOXOPLASMOSI S7) SUBARCHNOI D- - - GOOD HI STORY PLUS BLOOD I N CI STERN

THAT I S PROBABLY THE LI ST FOR CT HEAD. MOST LI KELY ASKED.

MRI1) CORONAL VI EW- - PI TUI TARY TUMOR2) ARNOLD CHI ARI SYNDROME3) SYRI NGOBULBI A/ MYELI A- - - DI LATED CENTRAL CANAL4) SPI NAL CORD COMPRESSI ON

THESE ARE THE MOST COMMON ONESSTART LOOKI NG UP I N THE FI RST BOOK FOR THESE SCANS AND UNDERSTAND THEM.NOW LOOK I NTO THE SECOND BOOK AND TRY TO DI AGNOSE THEMSEE WHAT MI STAKES YOU MADE AND THEN GO THRU THE THI RD BOOK AND GI VE THEDI AGNOSE . I CAN ALMOST BET THAT YOU WI LL SCOREMOST OF THEM CORRECTLY.

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ASHDOC

Ø Re: Wat er shed Ar eas- Br ai n- GI T – Spl eni c f l exur e and Rect osi gmoi d- wat ershed areas ar e ar eas where t here may be the f i r st si gn of anyvascul ar i nsul t . i n the br ai n the regi on suppl i ed by t he ACA and the MCAand l i kewi se i n t he GI T t he ar ea of t he col on suppl i ed by t he SMA andthe I MA. . . . . .- By di sul f i raml i ke:- Water shed areas are t hose r egi ons of t he cer ebr al cor t ex t hat are at

j unct i ons of maj or ar t er i al suppl i es. For exampl e, consi der t heant er i or cer ebr al art er y and mi ddl e cer ebr al ar t er y. The ant er i orcer ebr al ar t er y suppl i es t he r egi on of t he pr i mar y mot or cor t ex ( i . e.pr ecent r al gyrus) wi t h cel l bodi es of upper motor neur ons dest i ned t oevent ual l y synapse wi t h l ower mot or neur ons t hat serve t he l owerextr emi t i es. The mi ddl e cer ebr al ar t er y suppl i es t he r egi on of t hepr i mar y mot or cor t ex ( i . e. pr ecent r al gyrus) wi t h cel l bodi es of uppermot or neurons dest i ned t o eventual l y synpase wi t h l ower mot or neurons

t hat serve the f ace and upper ext r emi t i es. BUT - t he regi on of t hepr ecent r al gyrus cont ai ni ng t he cel l bodi es of upper motor neur ons t hatwi l l synapse wi t h l ower motor neurons dest i ned f or t he upperext r emt i ei s l i es BETWEEN THE TERRI TORY OF DI STRI BUTI ON OF THE ANTERI ORAND MI DDLE CEREBRAL ARTERI ES ( i . e. bet ween t he medi al par t of t hepr ecent r al gyr us and l at er al par t of t he pr ecent r al gyr us) . I T I S AWATERSHED AREA. BECAUSE I T I S POSI TI ONED FURTHEST AWAY FROM AN ARTERI ALSUPPLY, i t i s par t i cul ar l y suscept i bl e t o i schemi a. A WATERSHED I NFARCTproduces an i nf ar ct i on i n a wat er shed ar ea. A WATERSHED I NFARCT mayar i se f r omgl obal cer ebr al i schemi a secondary t o hypoper f usi on of t hecerebr al cor t ex ( e. g. f r om hear t f ai l ure) . BECAUSE THE WATERSHED AREASARE FURTHEST FROM ARTERI AL SUPPLI ES, THEY ARE PARTI CULARLY SUSCEPTI BLE

TO UNDERGO I NFARCTI ON. The ot her cl i ni cal l y si gni f i cant wat er shed ar eai s t he r egi on of t he cor t ex t hat l i es i n bet ween t he t er r i t or i es ofdi st r i but i on of t he mi ddl e cer ebr al and post er i or cerebr al ar t er i es.But , f r om my readi ng, t he water shed ar ea l yi ng at t he j unct i on of t het er r i t or i es of di st r i but i on of t he mi ddl e cer ebr al and ant er i orcer ebr al art er i es i s of most cl i ni cal si gni f i cance. SUCH A WATERSHEDI NFARCT WOULD PRODUCE HAND WEAKNESS.Ø Spi nal Cord Lesi ons:Amyot r ophi c l at eral scl erosi s: combi nat i on of UMN & LMN symptoms( pyr ami dal / ant er i or hor n cel l s)

Tabes dorsal i s: bi l at er al post er i or col umnsB12 def : post col umn & cor t i cospi nalPol i o: ant er i or hor n cel l sGui l l i an- bar r e: per i pher al ner ve i nvl t : mot or and sensor ySyri ngomyel i a: ant eri or whi t e commi ssure: bi l pai n and t emp l oss i n t ht

area onl yASA occl usi on : al l areas except t he post cl oumnsPSA occl usi on : i psi l at er al post col umn

Ø NERVE I NJ URI ES:LOWER LI MB: hey the f ol l n ar e ef f ect s of i nj ur i es t o the var i ousner ves( excl udi ng any over l aps)1) Super i or gl ut eal ner ve :suppl i es gl uteus medi us and mi ni mus

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weakness i n abducti on of t hi gh , i nabi l i t y to stabi l i ze pel vi s( t r endel enber g' s gai t )2) I nf er i or gl ut eal nerve :suppl i es Gl uteus maxi musweakness i n ext ensi on of t hi ghdi f f i cul t y get t i ng up f rom si t t i ng pos i t i on3)Femoral ner vesuppl i es ant er i or t hi gh muscl esweakness or l oss of f l exi on of hi p & extensi on of knee(ANASTHESI A OVERANTERI OR THI GH)4) Obtur at or nervesuppl i es medi al t hi gh muscl esweakness or l oss of adduct i on of t hi gh( ANASTHESI A OVER MEDI AL THI GH)5) Sci at i c ner vesuppl i es post er i or t hi gh muscl esl oss of f unct i on bel ow kneeweakness or l oss of ext ensi on of t hi gh & f l exi on of knees( ANASHTESI AOVER POSTERI OR THI GH)6) . Ti bi al nervesuppl i es post er i or l eg muscl es

l oss of i nver si on of f oot , l oss of pl ant ar f l exi on of f oot and f l exi onof t oes ( ALSO REMEMBER ANASTHESI A OF PLANTAR ASPOF FOOT& POSTERI OR LEG)7) Common peroneal nervesuppl i es muscl es of ant er ol ateral l eg r egi onLoss of dor si f l exi on of f oot ( f oot dr op)l oss of ext ensi on of t oes and l oss of evers i on of f oot ( ANASTHESI A OVERDORSAL ASP OF FOOT & ANTEROLAT LEG)

Ø Epi dur al hematomas ar e the resul t ( i n al most al l ci r cumst ances) ofskul l f r act ur es, wi t h shar p edges of bone cut t i ng i nt o t he dur alart eri es ( most l y t he mi ddl e meni ngeal art er y) whi ch l i e on t he out er( per i ost eal ) sur f ace of t he dur a.Ø We have t o know t hi s. . . t hey coul d gi ve a quest i on wi t h obst r uct i onand ask wher e the accumul at i on r esul t s. . . anyway, here i s t he f l ow ofCSF- - a mnemoni c: CSF LI VES I N THE CNS, FLOODI NG FORWARD ( LI KE ME) ,SPLASHI NG/ SWI MMI NG, AROUND.CSF = CHOROI D PLEXUS ( si t e of product i on)LI VES = LATERAL VENTRI CLEI N = I NTERVENTRI CULAR FORAMEN OF MONROE

THE = THI RD VENTRI CLECNS = CEREBRAL AQUEDUCTFLOODI NG = FOURTH VENTRI CLEFORWARD( LI KE ME) = FORAMEN OF LUSHKA AND MAGENDI ESPLASHI NG/ SWI MMI NG = SUBARACHNOI D SPACEAROUND = ARACHNOI D GRANULATI ONS ( si t e of r esor pt i on)

Ø EYE SI GNS:I f ound t hi s usef ul t abl e f r om CLI NI CAL NEUROANATOMY, by Waxman.

YOKE MUSCLE COMBI NATI ONSCARDI NAL DI RECTI ON OF GAZE- - - - - - - - - - - - - - - - - - - MUSCLE- - EYE UP, RI GHT- - - RT SUP RECTUS & LEFT I NF OBLI QUE- - EYES RT- - RT LATERAL RECTUS, LEFT MEDI AL RECTUS.- - EYES DOWN, RT- - - RT I NF RECTUS & LT SUP OBLI QUE.- - EYES DOWN, LEFT- - RT SUP OBLI QUE & LEFT I NF RECTUS.- - EYES LEFT- - - - - RT MEDI AL RECTUS & LEFT LATERAL RECTUS.- EYES UP, LEFT- - RT I NF OBLI QUE & LEFT SUP RECTUS

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- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -PARALYSI S OF I NDI VI DUAL MUSCLEMUSCLE- - - - - - NERVE- - - DEVI ATI ON OF- - - DI PLOPI A- - - DI ECTI ONOF I MAGEEYE BALL PRESENTWHEN LOOKI NG1. MED RECTUS- 3- - - OUTWARD( EXT SQUI NT) - - TOWARD NOSE- di r ect i on of i mage -ver t i cal .2. sup r ectus- 3- downward/ i nward- - upward/ out ward-di r ect i on of i mage- obl i que.3. i nf r ect us- 3- upward/ i nward- - downward/ out ward- di r ect i on of i mage-obl i que.4. i nf obl i que- 3- downward/ out ward- - upward/ i nward- di r ect i on of i mage- -obl i que.5. sup obl i que- 4- upward/ out ward- - downward/ i nward- -di r ect i on of i mage- obl i que.6. l at er al r ectus- - 6- - i nwar d( i nt er al squi nt ) - - t owar d t empl e.di r ecti on of i mage- ver t i cal

Ø what i s ext r a axi al br ai n hemorr hage and i nt r a axi al br ai n

hemor r hage?- Ans. Extr a- axi al bl eedi ng whi ch i s usual l y subdur al or epi dur albl eedi ng. Thi s i s bl ood t hat i s on t he sur f ace of t he br ai n and not i nt he subst ance of t he br ai n. Thi s has a charact eri st i c appearance asbr i ght col or on t he sur f ace of t he br ai n. A subdur al bl ood cl ot woul dbe bi concave or crescent i c i n appear ance. An epi dur al bl ood cl ot i schar act er i st i cal l y bi convex or l ent i cul ar i n appear ance.- I nt r aaxi al bl eedi ng i s a hemorr hage i n t he subst ance of t he br ai n andi t has no char act er i st i c appear ance except t hat i t i s i n t he br ai nmatt er and not on t he surf ace of t he br ai n.

Ø Vi sual Fi el d Def ect s- The pr obabl e l ocat i on of l esi ons pr oduci ng vi sual def ect s i s af avori t e USMLE t opi c ( and i s al so wel l wort h knowi ng i f you haveoccasi on t o work up such a pat i ent ) . Her e i s a l i st t hat may hel p yousort t hr ough t hese pr obl ems:Cent r al scot oma ~ macul aI psi l at er al bl i ndness ~ opt i c ner veBi t emporal hemi anopi a ~ opt i c chi asmHomonymous hemi anopi a ~ opt i c t r actUpper homonymous quadr antanopi a ~ t emporal opt i c r adi at i onsLower homonymous quadr ant anopi a ~ par i etal opt i c r adi at i onsAl so, cor t i cal l esi ons pr oduce def ect s si mi l ar t o t hose of t he opt i cr adi at i ons, but may spare t he macul a.

Ø Amyotr ophi c l at eral scl erosi s: combi nat i on of UMN & LMN symptoms( pyr ami dal / ant er i or hoen cel l s)

Tabes dorsal i s: bi l post er i or col umnsB12 def : post col umn & cor t i cospi nalPol i o: ant er i or hor n cel l sGui l l i an- bar r e: per i pher al ner ve i nvl t : mot or and sensor ySyri ngomyel i a: ant eri or whi t e commi ssure: bi l ater al pai n and t emp l ossi n t he ar ea onl y

Ø ASA occl usi on: al l areas except t he post cl oumnsPSA occl usi on: i psi l at er al post col umn

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NERVE I NJ URI I ES:LOWER LI MB: t he f ol l ng ar e ef f ect s of i nj ur i es t o t he var i ousner ves( excl udi ng any over l aps)1) Super i or gl ut eal ner ve:suppl i es gl uteus medi us and mi ni musweakness i n abducti on of t hi gh , i nabi l i t y to stabi l i ze pel vi s( t r endel enber g' s gai t )2) I nf er i or gl ut eal nerve:suppl i es Gl uteus maxi musweakness i n ext ensi on of t hi ghdi f f i cul t y get t i ng up f rom si t t i ng pos i t i on3) Femoral ner vesuppl i es ant er i or t hi gh muscl esweakness or l oss of f l exi on of hi p & extensi on of knee (ANESTHESI A OVERANTERI OR THI GH)4) Obt ur at or ner vesuppl i es medi al t hi gh muscl esweakness or l oss of adduct i on of t hi gh ( ANESTHESI A OVER MEDI AL THI GH)5) Sci at i c ner vesuppl i es post er i or t hi gh muscl es

l oss of f unct i on bel ow kneeweakness or l oss of ext ensi on of t hi gh & f l exi on of knees( ANESHTESI AOVER POSTERI OR THI GH)6) Ti bi al ner vesuppl i es post er i or l eg muscl esl oss of i nver si on of f oot , l oss of pl ant ar f l exi on of f oot and f l exi onof t oes ( ALSO REMEMBER ANESTHESI A OF PLANTAR ASP OF FOOT& POSTERI ORLEG)7) Common peroneal nervesuppl i es muscl es of ant er ol ateral l eg r egi onLoss of dor si f l exi on of f oot ( f oot dr op)l oss of ext ensi on of t oes and l oss of evers i on of f oot ( ANESTHESI A OVERDORSAL ASP OF FOOT & ANTEROLAT LEG)

Ø APHASI AS1] Aphasi a- - - unabl e t o repeat sent ence

Type - - Speech- Comprehensi on - Local i zat i ona] Expr essi ve ( Br oca) - - Nonf l uent - good - Lower post er i or f r ont alb] Recept i ve ( Wer ni cke) - - Fl uent - poor - Post er i or super i or t empor alc] Conduct i on- - Fl uent - good- Usual l y par i et al oper cul umd] Gl obal - - Nonf l uent - poor - Lar ge per i syl vi an l esi on

2] Aphasi a, abl e t o repeat sent ence wel l

Type- Speech - Comprehensi on - Local i zat i ona] Tanscor t i cal mot or - - Nonf l uent - good- Ant er i or t o Br oca' s ar ea or

suppl ement ary speech areab] Tr anscor t i cal sensor y - - Fl uent - poor- Sur r oundi ng Wer ni cke' s ar eapost er i or l y c] t r anscor t i cal mi xed - - Nonf l uent - poor - bot h of t he aboved] Anomi c- - Fl uent - good - Angul ar gyrus or second t emporal gyrus

The t erm appl i es t o t hose whose maj or sympt om i s wor d r et r i evaldi f f i cul t i es i n spont aneous speech and nami ng t asks. The spont aneousspeech of anomi c aphasi cs i s f l uent and gr ammat i cal l y cor r ect , but i smar ked by wor d r et r i eval f ai l ur es. The wor d r et r i eval f ai l ur es gener at eunusual pauses, ci r cuml ocut i on ( " t al ki ng around" mi ssi ng words) andsubst i t ut i on of nonspeci f i c wor ds such as " t hi ng" f or mi ssi ng wor ds.

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Ø A 55- year - ol d man compl ai ns of numbness i n bot h l egs and progr essi vei nabi l i t y t o wal k over t he past 2 mont hs. Physi cal exami nat i on i snormal except f or a decr eased per cept i on of l i ght t ouch and pai n i n thel ower ext r emi t i es as wel l as bi l ateral l eg weakness. Ther e i s nosensory l evel . Laborat ory workup i s r emarkabl e f or a hematocr i t of 30per cent and el evat ed t otal pr ot ei n. Ser um pr ot ei n el ect r ophor esi sr eveal s an M spi ke. The et i ol ogy of t hi s pati ent ' s weakness i s mostl i kel y

A necr osi s of cent r al ner vous syst em gr ay and whi t e matt erB i nf l ammat i on of dor sal r oot gangl i aC l oss of cer ebel l ar Pur ki nj e cel l sD el aborat i on of t umor- associ ated pr otei n t hat el i ci t s an i mmuner esponse t hat i s cross- r eact i ve wi t h per i pher al ner vesE tumor- el aborat ed i mmunogl obul i n that i s r eact i ng wi t h myel i ncomponent sAns. l ooks l i ke per i pher al neur ophat y, i n t hi s case coul d be as ar esul t of pr i mar y amyl oi dosi s (l i gt h chai n) so i go f or . . .

E- t umor- el aborat ed i mmunogl obul i n t hat i s r eact i ng wi t h myel i ncomponent s

Ø Pat i ent has meni ngi oma l ocat ed i n t he parasaggi t al r egi on of t he f al xcer ebr i , what neur ol ogi cal def i ci t mi ght t hi s pr oduce?. . . Ans. l egweakness or paral ysi s

Ø A 10 year ol d gi r l exhi bi t s neur ol ogi cal si gns, per f or mance i n schooldegener ates. sever al mont hs l ater she devel ops a sei zur e, ataxi a, andf ocal neur ol ogi cal sympt oms. She i s event ual l y quadr apar et i c, spasct i cand unr esponsi ve. She di es i n one year. What vi r al di sease di d t hi schi l d have at one year of age?. . and what i s t hi s di sor dercal l ed?. . . ans. measl es SSPE

Ø Wher e do myxopapi l l ar y ependymomas f r equent l y occur?medul l aponscer ebel l umconus medul l ari scer ebr al vent r i cl es ans. Conus Medul l ari sActual l y Fi l um t er mi nal e

Ø Lesi ons of whi ch ner ves wi l l pr oduce i mposi bi l l i t y of heel / t oewal ki ng? Ans. i mpossi bl e heal wi t h common per oneal & Ti bi al N 4 t hetoe. .

Ø BRS says that i n l esi ons of spi nal cor d:

- l es i on of l at eral cort i cospi nal t ract - - - > i ps i l at era l mot or def i ci t- l esi on of vent ral cort i cosp t ract - - - > cont ral at eral def i c i t

Thi s i s t r ue onl y when t he l esi on i s under pyrami dal decussat i on i nf i r st case and above spi nal decusat i on i n second case ri ght ? At whatl evel i s decussat i on of vent r al t r act ? Thanks. Ans. A l esi on of t hel at er al cor t i cospi nal t r act i n t he spi nal cor d bel ow t he decussat i onal ways r esul t s i n an i psi l at er al spast i c weakness bel ow t he l esi on. Thevent r al cor t i cospi nal t r act crosses at t he l evel of t he cer vi cal cor dwher e i t s axons i nnervate l ower mot or neurons t o neck muscl es. Ani sol at ed l esi on of t hi s t r act i n t he neck ( r ar e) may resul t i n a

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spast i c weakness of cer vi cal muscl es, but si nce t hi s t r act i s not wel lunder st ood, and r ar el y l esi oned i n i sol at i on, i t i s not a pr omi nentt est f eat ur e on t he USMLE.

Ø Name t he si t e of l esi on i n t he f ol l n: ( i woul d suggest u guys t o dr awa cut sect i on of br ai n st em or spi nal cor d and t hen go abt t hesequest i ons even t hough u wi l l be abl e t o guess t he l esi ons r i ghtaway. . wi l l be good f or t he exam. . )

- 1) Pt exper i ances decr esr ed pr opr i ocept i on i n l ef t upper ext r emi t y, decreased pai n- t emp sensat i on on r i ght si de of body bel ow neck, decreased pai n - t emp on l ef t hal f of f ace. .- 2) Cer ebel l ar dysf unct i on wi t h r i ght si ded at axi a, l oss of pai n- t empover r i ght f ace and l ef t body, hoar seness, di f f swal l owi ng, l oss of t ast eon r i ght , ver t i go &nyst agmus- 3) Lef t hemi pal egi a wi t h i nabi l t y of r i ght eye t o abduct- 4) Par al ysi s of r i ght l ower f aci al muscl es and r i ght upper ext r emi t yand i nabi l i t y t o adduct l ef t eye, l ef t pt osi s & di l at at i on of l ef tpupi l , t ongue devi at es t o r i ght- 5) Lef t si ded headache, t ot al par al ysi s of l ef t si de of f ace wi t h

ver t i go and l ef t si ded hear i ng l oss- 6) Nystagmus, bi l at er al i nt er nucl ear opht hal mopl egi a, cent r al scot omaof r i ght eye, weakness of r i ght l ower extr emi t y wi t h post i ve babi nski ,ur i nar y i ncont i nence, r i ght pt osi s and di f f i cul t y i n adducti ng r i ghteye- 7) Pt has no pupi l l ar y r eacti on at al l t o l i ght shi ned on l ef tsi de. t her e i s r eact i on t o l i ght i n bot h eyes when l i ght i s shi ned onri ght s i de- 8) Pupi l l ary r eacti on t o l i ght onl y on r i ght s i de. . whet her l i ght i sshi ned on l ef t or r i ght eye- 9) Pat i ent has i nabi l i t y t o move r i ght eye past mi dl i ne on at t empt edl ef t conj ugat e devi at i on but conver gence i s preser ved.- 10) Nei t her eye bl i nks on t ouchi ng r i ght cor nea but both eyes bl i nkon touchi ng l ef t cor nea- 11 ) Onl y l ef t eye bl i nks on t ouchi ng ei t her r i ght or l ef t cor nea- 12) Tremor of r i ght arms and l egs due to a red nucl eus l esi on. . Whi chr ed nucl eus i s af f ected r i ght or l ef t ?Ans.1) l ef t l ower medul l a2) r i ght upper medul l a3) r i ght pons4 l ef t mi d- br ai n5) l ef t si ded pont o cer ebel l ar t umor6) mul t i pl e scl er osi s7) l ef t CN 28) l ef t CN 39) r i ght medi al l ongi t udi nal f asi cul us

10) r i ght CN 511) r i ght CN 712) l ef t r ed nucl eus

Ø A 35 year ol d f emal e i s br ought t o t he emergency depar t ment by herhusband who says t hat she compl ai ned of severe headaches and t hen l ostconsci ousness. She i s unabl e to mover her ar ms and l egs, but can bl i nkher eyes. I n whi ch of t he f ol l owi ng st r uct ur es i s t hi s womans l esi onl ocat ed?cer vi cal spi nal cor d

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medul l a obl ongat ami dbrai nponst hal amusI was wonderi ng about t he quest i on. The answer can be Pons ( bi l ateralmedi al i nf er i or pont i ne syndr ome) but t her e wi l l be l oss of t act i l esensat i on f r omt he t r unk & ext r emi t i es ( Dorsal Col oumn medi al l amni scuspat hway) &CN 62nd answer can be medul l a - medi al medul l ar y syndrome caused by t hebasi l ar ar t er y but t her e wi l l ba agai n Dorsal col oumn medi al l amni scuspat hway damage & CN 12Accor di ng t o mysel f t hi s one can be t he Kernohan not ch caused by t hei ncr ease i n the i nt r acerebr al pr essur e causes t he damage t o t hecor t i cospi nal & cor t i cobul bar f i ber s agai nst t he t ent or i um cer ebel l iPl ease wr i t e t he expl anat i on i f you have

ThanksAns. t he pat i ent sust ai ned a hemorr hage t hat has dest r oyed her vent r alpons, descendi ng cor t i cospi nal and cor t i cobul bar f i ber s ar ei nt err upt ed. The pat i ent i s unabl e t o move t he f aci al , pharyngeal andl i mb muscul atur e, l eavi ng her par al yzed and unabl e t o speak. Thi s i s

l ocked i n syndr ome, pat i ent i s aware of bei ng l ocked wi t hi n her body.Onl y ver t i cal eye movement s and el evat i on of t he eyel i ds are possi bl e,so pat i ent i s bl i nki ng or movi ng t hei r eyes. Lesi ons of t he medul l at ypi cal l y i nvol ve t he medi al or l at er al aspect. l esi ons of t he l at er almedul l a i s known as t he post er i or i nf er i or cer ebel l ar ar t er y syndr ome,or wal l enber g syndrome

Ø Medi al i nf er i or pont i ne syndr ome:occl usi on of t he paramedi an br anches of t he basi l ar ar t er ySympt oms: 1) Loss of t he cont r al ater al spast i c hemi paresi s( Cor t i cospi nal t ract )2) Medi al Lamni scus Lesi on r esul t s cont r al at er al l oss of t act i l esensati on f r om t he t r unk & extr emi t i es3) Cn6 damage r esul t s i psi l ateral l at er al r ect us muscl e par al ysi s ( Thei mporant & easy di f f er ent i at i on)

Ø Carot i d ar t er y occl usi on : t her e ar e 2 car ot i d ar t er i es exter nal &i nt ernal . I do not know whi ch one r u t al ki ng about or about commoncaroti d art ery.

Ø Pont i ne l esi ons : t her e ar e 3 l esi ons1) Medi al i nf er i or pont i ne syndr ome Lat eral r ectus muscl e damage medi alst r abi sm i nabi l t y t o abduct t he eye2) AI CA : Horner ' s syndr ome3) MLF : her e eye wi l l devi ate t o the si de of l esi on CN3 pal sy causesmedi al r ect us muscl e damage r esul t s i n t he i nabi l i t y to adduct t he eye.

Ø On CSF: CSF f r om t he l umbar r egi on cont ai ns 15- 45 mg/ dl pr ot ei n and50- 80 mg/ dl gl ucose. Pr ot ei n concent r ati on i n ci st er nal and vent r i cul arCSF i s l ower. Normal CSF cont ai ns 0- 5 mononucl ear cel l s. The CSFpressure, measur ed at l umbar punct ure (LP) , i s 100- 150 mm of H2O wi t ht he pat i ent l yi ng on t he si de and 200- 300 mm wi t h t he pat i ent si t t i ngup.Ø CSF Bl ood Barr i er : I t ' s t i ght j unct i ons bet ween epandi mal cel l s. ( buti n bl ood br ai n bar r i er , ast r ocyt es+t i ght j uncti ons of endot hel i alcel l s) .

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Ø On Bact er i al Meni ngi t i s: Tabl e 2. Typi cal CSF f i ndi ngs i n pat i ents wi t h bact er i al ver sesnonbact er i al ( asept i c) meni ngi t i sCSF char acteri st i c- - Bacteri almeni ngi t i s- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - -

Openi ng pressure- - - - - El evat ed ( >180 mm H2O

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Whi t e bl ood cel l count - - I ncr eased (of t en >1, 000/ mm3) ,neut r opl i pr edomi nance- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Gl ucose l evel Decreased ( <40 mg/ dL)

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

- - - - - - - - -

CSF- serum gl ucose r at i o <0. 3- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Prot ei n l evel I ncr eased ( of t en >100 mg/ dL)

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Gr amst ai n r esul t s St ai nabl e organi sms pr esent i n 50%- 80% of unt r eatedcases

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Bacter i al cul t ure resul t s Posi t i ve

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

CSF, cer ebr ospi nal f l ui d.

> On Asept i c Meni ngi t i s:CSF char act er i st i c Nonbact er i al meni ngi t i s

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Openi ng pr essure Normal or sl i ght l y el evat ed

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Whi t e bl ood cel l count I ncr eased ( 10- 2, 000/ mm3) , l ymphocyt epredomi nance

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- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Gl ucose l eve; Normal ( >45 mg/ dL)

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

CSF- serum gl ucose r at i o >0. 6

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Pr ot ei n l evel Nor mal or i ncr eased

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Gr am st ai n resul t sNo st ai nabl e or gani sms

Bact er i al cul t ur e r esul t s Negat i ve

Ø Causes of Asept i c Meni ngi t i s:Vi r al i nf ecti on, SLE, Dr ugs ( I bupr of en?)

Ø ON FRONTAL LOBE TUMORS: t umors af f ect i ng t he f r ont al convexi t y, of t enproduce1] pr ogr essi ve hemi par esi s,2] f ocal or gener al i zed sei zur es, and3]ment al changes.

CONVULSI VE sei zur es may precede ot her sympt oms by mont hs or year s.APHASI A may accompany a t umor of t he DOMI NANT hemi spher e.A t umor at t he BASE of t he f r ont al l obes ( part i cul arl y meni ngi oma oft he ol f act ory gr oove) can produce I PSI LATERAL ANOSMI A;aAt umor on t he MEDI AL sur f ace can cause URI NARY URGENCY ori ncont i nence. MENTAL CHANGES, especi al l y i nat t ent i on and apathy, andat axi c gai t ar e common when t he t umor spr eads acr oss t he CORPUSCALLOSUM t o both f r ont al l obesØ ON PARI ETAL LOBE TUMORS:- May pr oduce gener al i zed or SENSORY f ocal sei zures. Cut aneous t act i l e,pai n, and t emper at ure senses are UNI MPAI RED,but STEREOGNOSI S and CORTI CAL SENSORY modal i t i es ( eg, posi t i on sense,t wo- poi nt di scri mi nat i on) ar e I MPAI RED cont r al at er al l y.- Cont r al at eral homonymous hemi anopi a, apr axi a, and anosognosi a ( nor ecogni t i on of bodi l y def ect s) may al so be pr esent .

- DENI AL of i l l ness i s charact er i st i c.- SPEECH di st urbances, AGRAFI A, and FI NGER agnosi a may occur when t het umor i nvol ves t he DOMI NANT hemi spher e.Ø ON TEMPORAL LOBE TUMORS:- par t i cul ar l y i n t he NONDOMI NANT hemi sphere, of t en produce FEWEARLYsympt oms but may cause convul si ve SEI ZURES- A t umor deep i n t he tempor al l obe may cause CONTRALATERAL HEMI ANOPI A,COMPLEX PARTAI L sei zur es, orconvul si ve sei zur es pr eceded by an OLFATORY AURA or VI SUALHALLUCI NATI ON of compl ex f or med I MAGES.

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- Tumors i nvol vi ng t he sur f ace of t he DOMI NANT t empor al l obe pr oduceMI XED EXPRESSI VE and RECEPTI VE AFASI A or dysphasi a, chi ef l y ANOMI AØ ON OCCI PI TAL LOBE TUMORS:- usual l y cause a CONTRALTERAL QUADRANT def ect or HEMI ANOPI A i n t hevi sual f i el d wi t h f unct i onal SPARI NG of t he MACULA. Sei zures may occur ,preceded by an AURA of FLASHI NG LI GHTS but NO f or med i magesØ ON SUBCORTI CAL TUMORS:- commonl y i nvol ve t he I NTERNAL CAPSULE and produce CONTRALATERALHEMI PLEGI A.- They may i nvade any l obe of t he hemi sphere, produci ng cor r espondi ngsympt oms.- THALAMI C i nvasi on pr oduces cont r al at eral CUTANEOUS sensor yi mpai r ment .- I nvasi on of t he basal gangl i a does not usual l y pr oduce parki nsoni ansympt oms but occasi onal l y pr oduces athet osi s, bi zarr e t r emors, ordystoni c post ur es.- Hypothal ami c t umors may pr oduce eat i ng di sorder s or , i n chi l dr en,pr ecoci ous puber t y

Ø BRAI NSTEM TUMOR:

- ar e usual l y gl i omas ( usual l y ast r ocyt omas) .Common symptoms, r esul t i ng f r om dest r uct i on of NUCLEAR masses, areuni l at er al or bi l at er al PARALYSI S of t he 5t h, 6t h, 7t h, and 10t hCRANI AL ner ves and PARALYSI S of LATERAL GAZE.- Damage to t he MOTOR or SENSORY pat hways causes hemi paresi s,hemi anest hesi a, or cer ebel l ar di st ur bances ( eg, at axi a, nystagmus,i nt ent i on t r emor ) .- I nt r acr ani al pr essur e i ncr eases l at e and onl y when tumors obst r uctt he aqueduct of Syl vi us.

Ø POSTERI OR FOSSA TUMOR:- i ncl udi ng t umor s of t he 4t h vent r i cl e and cer ebel l um ( usual l ymedul l obl ast omas, gl i omas, ependymomas, or metast ases) , i nt erf ere wi t hCSF ci r cul at i on and cause symptoms of I NCREASED I Cpressure ear l y.ATAXI C gai t , I NTENTI ON t r emor, and other si gns of cer ebel l ardysf unct i on f ol l owØ CEREBELLOPONTI NE TUMOR:- par t i cul ar l y NEURI LEMMOMAS(acoust i c neuromas, schwannomas) , arecharacter i zed by TI NNI TUS, uni l at eral hear i ng i mpai r ment , and somet i mesvert i go.- I f t he t umor i s LARGE, pr essur e on ADJ ACENT crani al ner ves, br ai nst em, and cer ebel l um pr oduces l oss of cor neal r ef l ex, f aci al pal sy andanest hesi a, pal at al weakness, si gns of cer ebel l ar dysf unct i on, and,r ar el y, cont r al at er al hemi pl egi a or hemi anest hesi a.- Loss of vest i bul ar r esponse to cal or i c st i mul at i on, enl ar gement oft he por us acust i cus seen on i magi ng scans, and HI GH CSF prot ei n cont entsuggest acoust i c neur oma

Ø Nondomi nant pari etal l obe l esi ons:- cont r al at er al ast er eognosi s&sensor y negl ect , anosognosi a, const r uct i onapr axi a, dr essi ng apr axi a, cont r al ateral hemi anopi a or l owerquadr ant anopi aØ What t r act s i nvol ved i n Fri edr i ech ataxi a? What t r act s i n Vi t B12di f f i ci ency? Ans. t he same t r act s ar e i nvol ved i n t hese 2 di seases: Vi tB12 di f f and Fri edr i ech at axi a ( AR di sease: pr ogr essi ve ataxi a,associ ated wi t h pes cavus, DM, kyphoscol i osi s, car di omyopathy) dorsalcol umns, l at er al cor t i cospi nal t r acts and spi nocer ebel l ar t r acts.

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Ø damage t o t hi s ner ve l eads t o l oss of f orear m pr onat i on? Ans. Medi anØ t he ner ve of adduct or pol l i ci s? Ans. ul nar ner veØ 1) A 23 year ol d man wi t h 10 year h/ s of compl ex par t i al sei zures andpi nki sh macul ar r ashes on hi s f ace. . wht i s t he di agnosi s. . wht ar e t heser ashes. . wht i s t he i nher i t ance pat t er n of t he d/ s?2) A 47 year ol d had r ecent l y compl eted a cour se of chemot her apy f orhi s acute myel oi d l eukaemi a some 6 days previ ousl y. The nur se i n char geasks you to exami ne t he pat i ent as he has not ed t he appearance of awi despr ead pet echi ae. He i s af ebr i l e and hi s cl ot t i ng i s nor mal . whtwud be the i mmed i nvest i gat i on and t r eat ment . . wht i s t he cause of t hesepet echi ae?3) A 40 year ol d house- wi f e was r ef er r ed t o the l ocal neur ol ogi st f ori nvest i gat i on of di zzy spel l s and sever al epi sodes of l oss ofconsci ousness. Accordi ng t o her husband, she had been wel l unt i l 4mont hs bef ore, si nce t hen he had not ed 3 occasi ons when he f ound i tdi f f i cul t t o wake her up i n t he morni ngs. The GP was cal l ed i n, but byt he t i me he ar r i ved t he pat i ent was awake and compl ai ni ng of aheadache. No obvi ous cause was f ound f or t hese epi sodes. 1 mont hpr evi ousl y, af t er dr i nki ng 2 Gi n and Toni cs, she became unusual l ydr owsy- t hi s l ast ed f or about 15 mi nut es. Fol l owi ng t hi s, i t was noted

t hat she became t al kat i ve, but was speaki ng nonsense f or a f ur t her 5mi nutes. Thr ee weeks bef ore admi ssi on she had an epi l ept i c sei zurewhi l st at her daught er ' s weddi ng. Ther e was no past medi cal hi st ory ofnote, al t hough she had gai ned 5 kg i n wei ght i n t he l ast 3 mont hs.General medi cal exami nat i on was unr emarkabl e. Pul se was 75/ mi n SR, bp130/ 85. Apar t f r om her br i sk tendon r ef l exes, neur ol ogi cal exami nat i onwas l i kewi se unr emarkabl e, wi t h f l exor pl ant ar s.wht i s t he l i kel y di agnosi s?wht ar e t he i nvest i gat i on?Ans. ????Ø i ons have hi gher l evel s i n CSF when compared t o pl asma? Ans. comparedt o ser um, CSF has t he same concent r at i on of Na+,hi gher Mg++, Cland l ower K+, Ca++, HCO3, Gl ucose, Pr ot ei nØ t he l ocat i on of Locus coer ul eus?and r el ated neur ot r ansmi t t er ? Ans.

j ust l at er al t o t he f l oor of 4t h ventr i cl e, yes NEØ CNS st r uct ur es wi t hout BBB( Bl ood Br ai n Barr i er) ? Ans. choroi d pl exusand al so medi an emi nence, neur ohypophysi s, l ami na t ermi nal i s, pi nealgl and.Ø t he pr esent at i on of conduct i on aphasi a? Ans. poor r epet i t i on, goodcomprehensi on, f l uent speech…yes! paraphasi as( use of i ncor r ectwor ds) , poor obj ect nami ng, sever e def i ci t of r epet i t i on andf l uent speech i s of t en i ndi r ect( ci r cuml ocut or y) .Ø Name the t i ssue t hat does not ut i l i ze gl ucose as t he pr i mary f uelsour ce. What does i t ut i l i ze t hen? Ans. car di ac bet a oxi dat i on of f at t yaci ds. . . .Ø Werni cke’ s aphai a somet i mes mi sdi agnosed as psychosi s, why? Ans. bcozt hey usual l y have no hemi paresi s, no depr essi on, i nst ead euphori c, absence

of neur ol ogi c si gns pl us bi zar r e speech and abbehavi or, agi t at i on, paranoi d t hought s t hat somet i mes seen, l ead t oi ncor r ect di agnosi s of f unct i onal psychosi sØ WHERE I S THE CHEMORECEPTOR TRI GGER ZONE LOCATED?PONS3RD VENTRI CULE4TH VENTRI CULEFRONTALE LOBEMEDULA ans. r ostr al vent r ol ateral medul l a. . .Ø

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HI STOLOGY

Ø Cal l - Exner bodi es: Gr anul osa/ t heca cel l t umor of ovaryCounci l man bodi es: Hepat i t i s: t oxi c or vi r alCowdry t ype A bodi es: HSV, SSPERussel bodi es: Mul t i pl e myel omaMal l or y' s bodi es: Chr oni c al chohol i c hepat i t i sSchi l l er - Duval bodi es: Yol k Sac t umor

Ø SOME HI GH YI ELD NOTES FOR CELL BI OLOGY & HI STOLOGY, CELL AND TI SSUEBI OLOGY

I NTRODUCTORY STUFFDYES:Dye St r uct ur e:

Chr omophore Gr oup: The chemi cal moi ety of t he dye that i s r esponsi bl ef or i t s col or .Auxochr ome Gr oup: The moi ety on t he dye that bi nds t o t he cel l ul arcomponent s. I t i s usual l y ei t her ami no or SO42- gr oups.Ami no auxochr ome group = a basi c dye.Sul f at e auxochr ome gr oup = an aci di c dye.Common types of st ai ns:Hemat oxyl i n and Eosi n ( H&E) : Most common t ype of st ai n.Hemat oxyl i n: Funct i onal l y a basi c dye ( despi t e t he f act t hat i t i sani oni c) . I t bi nds t o basophi l i c (negat i vel y char ged) nucl earcomponent s l i ke DNA and RNA.I t stai ns bl ueEosi n: Aci di c dye. I t bi nds t o posi t i vel y char ged, aci dophi l i ccomponents.I t stai ns pi nk t o r ed.Masson (Tri chr ome) St ai n:Col l agen i s gr een.El asti c f i bers are red.ACI DOPHI LI C: At t r acted t o aci di c subst ances, whi ch are ani oni c( negat i vel y char ged) at physi ol ogi c pH. Thus aci dophi l i c subst ances areposi t i vel y char ged.

Pr ot ei ns ar e aci dophi l i c i n at a pH hi gher ( mor e basi c) t han t hei ri soel ect r i c poi nt . When t he envi r onment al pH i s above a pr otei n' si soel ect r i c poi nt , t he pr ot ei n i s posi t i vel y char ged and henceaci dophi l i c.Many pr ot ei ns are aci dophi l i c at physi ol ogi c pH.

Aci dophi l i c Component s:BASOPHI LI C: At t r act ed t o basi c subst ances, whi ch are cat i oni c( posi t i vel y char ged) at physi ol ogi c pH. Thus basophi l i c subst ances arenegat i vel y charged.

Pr ot ei ns are basophi l i c at a pH l ower ( mor e aci di c) t han t hei ri soel ect r i c poi nt . When the envi r onment al pH i s bel ow a pr ot ei n' si soel ect r i c poi nt , t he pr ot ei n i s negati vel y char ged and hencebasophi l i c.Basophi l i c Component s:

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DNA and RNA = basophi l i c due t o presence of phosphat e gr oups.Prot eogl ycans = basophi l i c due t o sugars and est er i f i ed sul f ates whi char e negat i ve at physi ol ogi c pH.Speci al Types of St ai ni ng Techni ques:

Metachr omasi a: A subst ance can take on a di f f erent t han expected col orwhen t he subst ance has t wo chemi cal l y react i ve gr oups that i nt eract duet o t hei r cl ose pr oxi mi t y.Fat - St ai ni ng: To st ai n membr anes and l i pi d- materi al s, you must use af at - i nsol ubl e sol vent and f r eeze- f r acturi ng. You can' t use par af f i nbecause i t woul d di ssol ve t he subst ance!Common sol vent s i ncl ude pr opyl ene gl ycol , and ethanol .Sudan I V i s a t ypi cal f at - sol ubl e dye.

The Schi f f Reagent - - speci f i c f or DNA and pol ysacchar i des.Feul gen React i on: Thi s r eact i on uses Leucof uchsi n as a dye, whi chsel ect i vel y stai ns pur i nes i n DNA.Per i odi c Aci d- Schi f f ( PAS) React i on: Sel ect i vel y st ai ns pol yhexoses andhexosami nes. Ti ssues st ai ned by t hi s r eact i on i ncl ude:Gl ycogenEpi t hel i al muci ns i n gobl et cel l s.

Prot eogl ycans i n basement membranes - - but not of t he CT mat r i x.Enzymat i c Stai ni ng: For exampl e, you can vi sual i ze mi t ochondr i a byt est i ng f or t he pr oduct of a mi t ochondr i al enzyme. The i mport ant poi nti s t hat t he enzyme i s not st ai ned di r ect l y i n t hese pr ocedur es. Rat her ,t he l ocal i zat i on of i t s act i vi t y i s tested f or .I mmunohi st ochemi st r y:Fl uorescent Ant i body Techni que: Compl ex a f l uorescent dye wi t h anant i body t hat bi nds t o speci f i c ant i gens on t i ssues t hat you want t ovi sual i ze.I ndi r ect I mmunof l uorescence: Vi sual i zati on of a ti ssue usi ng t woant i bodi es, wher e t he t ar get st r uct ur e t hat i s act ual l y vi sual i zed i sbound t o the second ant i body.I ndi r ect I mmunocytochemi st r y: Si mi l ar t o i ndi r ect i mmunof l uorescence,but el i mi nat i ng t he need f or f l uor escent vi sual i zat i on.Prot ei n- A Gol d Techni que:Aut oradi ogr aphy: bet a- el ect r ons i nt er act i ng wi t h si l ver br omi de ( AgBr )cryst al s f r om r adi oacti ve mat er i al s i l l umi nat es radi oacti ve st r uctures.El ect r on Mi croscopy:St ai ni ng i s usual l y wi t h osmi um.Some sor t of f i xat i on i s r equi r ed - - such as Freeze Fract ur e, i n whi chwe cut a pr eparat i on i nt o t hi n sl i ces usi ng a mi cr otome.

PLASMA MEMBRANE AND BASI C CELLULAR STRUCTURESFLUI D MOSAI C MODEL:

RED- BLOOD CELLS GHOSTS: Put a RBC i n sal t and cr ack t he membrane ( i . e.make i t l eaky) so t hat al l cont ent s l eak out . Then reseal t he membr ane,

and we are l ef t wi t h t opography maps of t he RBC- membrane, showi ngper i pher al and i nt egr al membr ane- pr otei ns.

I nt egral Protei ns:Gl ycophori n: Has ext ensi ve sacchari de gr oups on t he exter i or sur f ace.I t i s a s i ngl e- pass protei n.Band- I I I : Per i pher al ani on channel , exchangi ng HCO3- out f or Cl - i n.I t i s a mul t i - pass i nt egr al membr ane pr ot ei n.

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Band- I I I has no l at er al mobi l i t y i n t he membr ane - - i t i s hookeddi r ectl y t o t he cyt oskel et on vi a Ankyr i n - - - - - - > Spectr i n - - - - - - > Acti nspokes.Rhodopsi n: The "mother " of t he 7- pass al pha- hel i cal mul t i - passt r ansmembrane pr otei n ( of t he adr energi c G- pr ot ei n- bound r eceptorf ami l y) . Thi s i s a gener al cl ass of i nt egr al pr ot ei ns and descri bes al ot of di f f erent protei ns.Per i pher al Pr ot ei nsAnkyr i n i s connected t o t he i nsi de per i phery of t he RBC membr ane.Spect r i n i s hooked t o membr ane vi a Ankyr i n.Spect r i n f orms a l at t i ce network composed of al pha and beta di mers .I t hooks ont o Band- I I I i n the membr ane ( vi a ankyr i n) at one end, andont o Act i n at t he spokes of t he RBC- cyt oskel et on i n the RBC i nt er i or.Band 4. 1: Another per i pher al pr otei n t hat hel ps anchor spect r i n andact i n to t he RBC membrane.Her edi t ary Spher ocyt osi s: Hemol yt i c anemi a caused by a f ai l ur e f orRBC' s t o f or m a bi concave di sc and t her ef or e i nabi l i t y to squeezet hrough capi l l ar i es.I t can be caused by any of a number of genet i c mutat i ons i n RBCcyt oskel et al pr ot ei ns.

One f orm i s caused by a mut at i on i n Ankyr i n whi ch r esul t s i n badspl i ci ng. Ther e i s a 2. 1 and 2. 2 spl i ce out of t he same pr ecur sor mRNA.2. 1 spl i ce: pr edomi nant i n devel opi ng cel l s.2. 2 spl i ce r equi r ed i n mat ur e cel l s.

The 2. 2 spl i ce di sappears wi t h t he mi sspl i ci ng mut at i on, hence RBC' smatur e but t hey don' t f unct i on when f ul l y devel oped.At t he same t i me, ot her ankyr i n i sof orms of t he same RNA precur sor aret r ansl at ed nor mal l y, but t hey ar e i n ot her cel l - t ypes.

GLYCOSYLATI ON:N- Li nked Gl ycosyl at i onSugar hooks ont o Asparagi ne Resi due.Common Sugars at t ached are N- Acet yl gl ucosami ne ( Gl uNAc) , and MannoseGl ycosyl ati on occur s cotr ansl at i onal l y, i n t he Rough ER.PROCESS:Cor e Gl ycosyl at i on event occur s i ni t i al l y. I t i nvol ves t he l i nkage oft he cor e ol i gosacchar i de.

The cor e ol i gosacchar i de i s t hen associ at ed t o t he l i pi d compl ex,dol i chol phosphat e. Then i t i s di sassoci at ed and l i nked t o t he pr ot ei ni n one st ep.O- Li nked Gl ycosyl at i onSugars hook onto Ser i ne or Thr eoni ne r esi dues.Common sugars at t ached are N- Acet yl Neur ami ni c ( Si al i c) Aci d and N-Acet yl gal act osami ne.Gl ycosyl at i on occur s post t r ansl at i onal l y, i n t he Gol gi .Exper i ment s t o Demonst r ate t he Fl ui d- Mosai c Model : Li pi ds can movel at er al l y and can wi ggl e t hei r hydr ophobi c t ai l s ver y rapi dl y, but t hey

can' t f l i p- f l op wi t hout a speci al cat al yt i c reacti on ( cat al yzed byf l i ppase) .

Het er okar yon Experi ment : Showed the movement of membrane pr ot ei nswi t hi n the pl asma membrane of a human- mouse hybr i d.Fl uorescence Recover y Af t er Photobl eachi ng ( FRAP) : A way to show t hatl at eral movement of membrane pr ot ei ns occur s.

You can determi ne a Di f f usi on Coef f i ci ent f or Lat eral Mobi l i t y. Somecommon coef f i ci ent s:Phosphol i pi ds i n membranes: 1 x 10- 8 cm2/ sec

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Most hi ghl y mobi l e membrane pr ot ei n (Rhodopsi n) : 5 x 10- 9 cm2/ sec You st ar t wi t h 100% f l uorescence i n membrane, t hen zap wi t h bl each al i t t l e spot on t he membrane, and the f l uor escence goes way down t oabout zero.

Then you can wat ch t he f l uorescence r ecover ( back up t o near 100%) asadj acent l i pi ds and/ or pr ot ei ns di f f use t o the bl eached ar ea.Rest r i ct ed Mobi l i t y: The cyt oskel et on i n r ed bl ood cel l s restr i ct s t hemobi l i t y of many membrane pr ot ei ns on t he RBC membrane.

Cytoskel etal El ement s: Fi l ament Type Si ze Composi t i onMi cr of i l ament s 7- 8 nm Act i n monomersI nt ermedi ate Fi l ament s 10 nm var i abl eMi cr ot ubul es 25 nmal pha and bet a t ubul i n monomersMyosi n ( Thi ck) Fi l ament s var i abl e Myosi n

Mi cr ot ubul es:Made of di mer s of al pha and bet a t ubul i n. They wi l l sel f - assembl e( aut opol ymer i ze) under t he r i ght condi t i ons.Pol ar i t y( +) - End: Tubul i n monomers ar e, on aver age, bei ng added to t hi s end. New

monomer s are put on at a f ast er r ate t han t hey f al l of f .( - ) - End: Tubul i n monomers are, on average, bei ng r emoved f r om t hi s end.Monomer s f al l of f at a f ast er r at e than t hey ar e put on.Mi cr otubul e Or gani zi ng Cent er ( MTOC) : Of t en f ound ar ound cent r i ol es.Mi crot ubul es hook to cent r i ol es by t hei r ( - ) - ends.

Tr ead mi l l i ng Ef f ect : I f you l abel one monomer on a mi cr ot ubul e, i twi l l appear as i f i t magi cal l y moves f r om t he pl us t o the mi nus end.

That ' s because we keep addi ng new monomers t o t he pl us end, so i t getspushed f ur t her back i n t he chai n, unt i l f i nal l y i t i s al l t he wayt oward the mi nus end and i t f al l s of f t he chai n.Ant i - Mi cr ot ubul e Dr ugs:Col chi ci ne: Bi nds t o t ubul i n monomers and thereby pr event s assembl y ofmi crot ubul es, ki l l i ng t he cel l .

Taxol : Cont r over si al new ant i - cancer drug t hat wor ks i n t he exactopposi t e way as t r adi t i onal dr ugs. I t st abi l i zes t he mi crot ubul ef i l ament so that i t can' t di sassembl e. The resul t i s t he same, however :mi cr ot ubul e dynami cs are l ost and the cel l di es.CYTOSKELETAL MOTOR PROTEI NS: ATPases t hat cl eave ATP t o cause movement .

The mi cr ot ubul es / act i n don' t move t hemsel ves. Rat her i t i s t hei nt er act i on of t he mot or prot ei ns wi t h t he tubul es t hat causesmovement .

Myosi n: Act i n- bi ndi ng pr ot ei n.Dynei n: ( - ) - End Or i ent ed Mi cr ot ubul e bi ndi ng pr ot ei n.I t moves al ong t he mi cr ot ubul es f r om t he ( +) t o t he ( - ) end. I tt her ef or e f aci l i t at es r et r ogr ade axonal t r anspor t .

Tai l i s t he r egi on t hat at t aches t o t he mi cr ot ubul es. The Head i s t he

ATPase r egi on.Ki nesi n: ( +) - End Or i ent ed Mi crot ubul e bi ndi ng pr ot ei n.I t moves al ong t he mi cr ot ubul es f r om t he ( - ) t o t he ( +) end. I tt her ef or e f aci l i t at es ant er ogr ade axonal t r anspor t .Ci l i a/ Fl agel l a: The mi nus end i s t owar d t he t i p, and t he ( +) - end i st owar d t he basal body, t owar d t he pl asma membrane.

I NTERMEDI ATE FI LAMENTS: Made of kerat i ns, desmi n, vi ment i n, andneur of i l ament s.

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NUCLEAR TARGETI NG of PROTEI NS:Nucl ear Por es: Have speci f i c t ar get i ng si gnal s f or nucl eus- boundpr otei ns. Por es ar e f ormed at poi nt s wher e the i nner and out er l ayersof t he Nucl ear bi - membrane come t ogether .EXPT: The Lar ge- T Ant i gen of t he SP40 vi r us was seen i n the nucl eus ofa host cel l by i mmunocyt ochemi cal i magi ng.A mut at i on on t he T- Ant i gen si t e, exchangi ng a Lysi ne f or a Thr eoni ne,caused sort i ng t o occur i n t he cyt osol i nst ead.

Thus t hi s mut at i on was part of t he Nucl ear - Target i ng Sequence.EXPT: Frog oocyt es - - t he resul t s suggest ed that t he nucl ear t ar get i ngsequence was on t he tai l subuni t of t he nucl eopl asmi n pr otei n i n f r ogoocyt es.When the head and tai l wer e di ssoci ated, t he tai l was abl e to t hr oughnucl ear membrane and head wasn' t .Al so, i f col l oi dal gol d part i c l es are associ at ed wi t h t hi s tai lsubuni t , t hey, t oo, can get i nt o the nucl eus, but onl y i f ATP i spr esent .SUMMARY:

Tr anspor t i nt o t he nucl eus does not t ake pl ace by passi ve di f f usi on. I tt akes by hi ghl y speci f i c t r anspor t wi t h t ar get i ng sequences.

I t appear s t hat nucl ear t r anspor t i s an act i ve pr ocess ( at l east i nf r og oocyt es) . I t r equi r es ATP.ROUGH ENDOPLASMI C RETI CULUM: Cyt osol i c pr ot ei ns can be synt hesi zed onf r ee r i bosomes i nst ead of t he Rough ER, per se. However, t he f ol l owi ngpr ot ei ns ar e al ways synt hesi zed on t he Rough ER:

Membrane Protei ns: Usi ng Si gnal Pept i des and Si gnal Recogni t i onPar t i cl es, t hey ar e di r ect l y t r ansl at ed i nt o t he membr ane, wher e theystay.Secr eted Prot ei ns: They are exuded i nto the ER l umen, and t hen ont oGol gi and f i nal l y secr eted i n vesi cl es. They must be synt hesi zed on ERt her ef or e.

MI TOCHONDRI A: Protei ns dest i ned f or t he mi t ochondr i a ar e i nt egr atedi nt o t he mi t ochondr i al membr ane post - t r ansl at i onal l y. Fi r st t hey ar esynt hesi zed, and t hen t hey go t o mi t ochondr i a vi a a vesi cl e.

GOLGI COMPLEX:Ci s Gol gi : Ear l i est par t of Gol gi , cl osest t o t he ER.

Tr ansi t i on Vesi cl es of t en t r anspor t mat er i al f r om t he ER t o t he Gol gi .Mi ddl e Gol gi

Tr ans Gol gi : Par t of Gol gi of f of whi ch vesi cl e bud.

ENDOCYTOSI S: Cl athr i n associ ated wi t h a r ecept or pr otei n, whi ch i n tur nassoci at ed wi t h t he membrane.

Ther e ar e sever al adapt er prot ei ns, dependi ng on t he membrane t o whi ch

t he vesi cl e wi l l f use. For exampl e, t her e i s a speci f i c adapt er pr ot ei nf or t he Gol gi .

The di f f er ence i n adapt er prot ei ns between

LYSOSOMAL STORAGE DI SEASES: Lot s of di seases have at l east one et i ol ogywher e t he mut at i on l i es i n i ncor r ect sor t i ng of t he pr ot ei n, r at hert han a non- f uncti onal pr ot ei n i t sel f .

I - Cel l Di sease:

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The Mannose- 6- Phosphat e r ecogni t i on mar ker i s f ound on one of t he N-Li nked Ol i gosacchar i des of a l ysosomal hydr ol ase. I t t ar get s t hepr otei n f or t he l ysosome. Addi ng t he M6P i s a t wo st ep pr ocess.

One enzyme put s on N- Acet yl gl ucosami ne phosphate ont o a mannoser esi due.A second enzyme t hen removes t he N- Acet yl gl ucosami ne, l eavi ng Mannose-6- Phosphate i n i t s wake.I t i s t he f i r st st ep, addi t i on of N- Acet yl gl ucosami ne phosphat e, t hatgoes wr ong i n I -Cel l di sease.

Cysti c Fi brosi s: The CFTR prot ei n i s most l y get t i ng made, but i t i s not get t i ngt r anspor t ed t o the Gol gi . The pr i mar y et i ol ogy of t he di sease i s asor t i ng pr obl em, not a def ect i ve pr ot ei n.

Tay- Sach' s Di sease:Agai n, one of t he causes i s a mi ssort i ng of t he pr ot ei n bet a-Hexosami ni dase, wher e i t can' t get f r omER t o Gol gi .

Emphysema and Fami l i al Hyper chol est erol emi a are t wo more exampl es.

Sucr ase- I somal t ase Def i ci ency: The Sucr ase- I somal t ase enzyme i s normal l y t ar geted t o t he api calepi t hel i al membr ane and i s i nvol ved wi t h di sacchari de / gl ycogenbreakdown.I ndi vi dual s wi t h t he def ect can' t met abol i ze l ong- chai n sugar s.Agai n i t seems t hat t he secr etory pathway f or t he enzyme i s bl ocked.

EPI THELI AEPI THELI AL CELL TYPES:Si mpl e Squamous Epi t hel i um: Ki dney Bowman' s Capsul eResembl e f r i ed eggs i n shape.Si mpl e Cuboi dal Epi t hel i um: Ki dney Col l ect i ng Tubul eKi dney tubul es cel l s ar e speci al i zed f or absor bi ng sal t and water i n anapi cal t o basal di r ecti on.Si mpl e Col umnar Epi t hel i um: GI Tract ( Stomach, J ej unum, Duodenum,I l eum)Ot her Ti ssues: Gal l Bl adder and Ut er i ne Gl and.Si mpl e Col umnar Cel l s ar e speci al i zed f or one or al l of t hr ee t hi ngs:Secr et i onPr ot ect i onAbsorpti on: Thi s i s especi al l y t r ue i n Duodenum and J ej unum.

They have oval nucl ei t owar d t he basal si de.SI MPLE COLUMNAR EPI THELI UM CELL TYPES: There ar e f our basi c cel l t ypesof si mpl e col umnar epi t hel i aCol umnar

Fus i f ormBasalGobl et : = Modi f i ed col umnar cel l s t hat synt hesi ze and secrete mucous.St er eoci l i a ar e "ci l i a" t hat don' t move, but t hey ar e act ual l y ver yl ong mi crovi l l i speci al i zed f or absor pt i on, and onl y vi si bl e at EMl evel .Pseudost r at i f i ed Col umnar Epi t hel i um: Trachea and Upper Respi r atory

Tr act The t r achea i s act ual l y ci l i at ed, but t here ar e al so non- ci l i at edpseudost r at i f i ed col umnar epi t hel i a.

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Exampl e of Pseudost r at i f i ed Non- Ci l i ated Col umnar Epi t hel i um: Mal eUr et hr aSt r ati f i ed Squamous Epi t hel i um: Sal i var y Gl ands, Ski n, Vagi nal Wal l

Ther e was no exampl e of t hi s i n t he car ousel s but onl y f i nal t est i ngsl i de.St r ati f i ed Squamous Ker at i ni zed: Layer of Ker at i n on t op, as i n Ski n.St r at i f i ed Squamous Non- Ker at i ni zed ( Mucosal ) : No Kerat i n on api calsur f ace, as i n Vagi na and Mout h.St rat i f i ed cel l s f orm t he f ol l owi ng l ayers:Basal End: Cuboi dal Cel l s t hat ar e pr ol i f er at i ve.Mi ddl e: Pol ygonal cel l s hel d t ogether by desmosomes.Api cal End: Squamous Cel l s t hat are non- pr ol i f er at i ve.St r ati f i ed Cuboi dal Epi t hel i um: Sweat Duct of Ski n

Tr ansi t i onal Epi t hel i um: Ur i nary Bl adder The t i ssue appears t o t r ansf or m f r om 5- 8 l ayer s when empt y, t o 2- 4l ayer s when t he bl adder i s f i l l ed. The cel l s can squi sh t oget her .EPI THELI AL Gener al Char act er i st i cs

AVASCULAR: Epi t hel i al Ti ssue i s gener al l y avascul ar .POLARI TY: Epi t hel i al cel l have pol ar i t y.

The api cal si de of t en cont ai ns mi cr ovi l l i and f aces t he l umen ofwhat ever sur f ace t he epi t hel i um l i nes.Mi crovi l l i ar e char acteri st i cal l y f ound on api cal domai n. Acti nf i l ament s ar e associ at ed wi t h t he mi cr ovi l l i , f or mi ng t he t er mi nal web.Ci l i a ar e f ound on api cal membr ane, i n ci l i at ed cel l s.

The basal si de i s opposi t e t hat . A basement membrane, consi st i ng of abasal l ami na and r et i cul ar l ami na, of t en under l i es t hat .

The Na+/ K+- ATPase pump i s char act er i st i cal l y onl y f ound on t hebasol at eral membrane.BASEMENT MEMBRANE: The basal l ami na i s vi si bl e onl y at t he EM l evel .

The Basement Membrane, on t he basal sur f ace, i s avai l abl e at t he LMl evel and consi st s of t he basal l ami na pl us t he under l yi ng connect i vet i ssue.MESOTHELI UM: Mesodermal l y deri ved epi t hel i um t hat l i nes body cavi t i es.

TERMI NAL WEB: Vi si bl e networ k of act i n f i l ament on t he api cal end of anepi thel i al cel l .

J UNCTI ONAL COMPLEX: The j unct i onal compl ex keeps t he api cal and basalsi des of t he epi t hel i um separ at e f r om each ot her .

Zonul a Occl udens: Ti ght J unct i ons. They al l ow f or sel ect i ve passage ofpar t i cl es, and t hey pr event par t i cl es f r om get t i ng st uck bet ween cel l sor get t i ng i nt o t he l umen.Zonul a Adher ens: Al so pr esent at t he j unct i onal compl ex.Macul a Adherens: Desmosome. I t goes al l t he way ar ound t heci r cumf er ence of t he cel l , l i ke a bel t or a spot wel d.

TERMI NAL BAR: Zonul a Occl udens + Zonul a Adher ens.

Gap J unct i on: Bel i eved to medi at e el ect r oni c coupl i ng bet ween cel l s.Dye can squeeze t hr ough a gap j unct i on t o get one f r omcel l t o t henei ghbor .POLARI TY EXPT: Cel l s l ost t hei r pol ar i t y by di sassoci at i ng and t henr eassoci at i ng cel l s such t hat t hey l ose t hei r i nt er cel l ul ar cont acts.

The Na/ K ATPase pump occurs onl y on t he basal membrane of t he cel l .Vi r al EXPTs: You can al so st udy t he di st r i but i on of vi r al pr ot ei ns t ost udy t he host - cel l ' s machi ner y, si nce t he vi r us uses t he host - cel l ' smachi ner y.

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Peopl e have wat ched wher e vi r al capsi d pr ot ei ns went when theyassoci at ed wi t h t he host pl asma membrane.

The I nf l uenza Vi r us onl y di st r i buted prot ei ns t o t he api cal end of anepi thel i al cel l .PATHWAYS f or Expl ai ni ng Pol ar i t y: Two al t ernat i ve methods have beenf i gur ed out .

Target i ng Mechani sm where a cl ass of vesi cl es speci f i cal l y r ecogni zepr ot ei ns on t he api cal domai n. Hence some prot ei ns wi l l onl y merge wi t hmembrane on t he api cal domai n.

Tr anscyt osi s: Some evi dence al so suggest s t hat prot ei ns ar e i ni t i al l ysor t ed i n t he basal domai n, and t hen l at er t r ansf er r ed t o the api caldomai n vi a t r anscyt osi s.EPI THELI AL EXOCRI NE GLANDS:

Uni cel l ul ar : Gobl et Cel l s ar e uni cel l ul ar exocri ne gl ands.Si mpl e Tubul arSi mpl e Br anched Tubul arSi mpl e Al veol arSi mpl e Br anched Al veol arCompound Tubul ar

Compound Al veol arCompound Br anched Tubul arCompound Br anched Al veol ar

THE CELL CYCLE Types of Cel l s Cycl es:Chromosomal Cycl eCent r osomal Cycl e: The Cent r i ol es dupl i cat e t hemsel ves pr i or t omi t osi s, and move to opposi t e pol es.Cyt opl asmi c Cycl e: Ref er s t o cyt oki nesi s. Di st r i but i on andr edi st r i but i on of cyt opl asm.Phosphoryl at i on Cycl e: Phosphoryl at i on pr omotes mi t osi s, as di scussedl at er .Nucl ear Membrane Cycl e: Nucl ear Lami ns are phosphoryl at ed dur i ngProphase, whi ch causes t hem t o di ssoci ate and resul t s i n br eakdown t henucl ear membrane.Nucl ear l ami ns ar e a f orm of i nt er medi at e f i l ament .Nucl ear Lami ns ar e dephosphoryl at ed duri ng tel ophase, so t heyr eassoci at e and membrane r ef orms.

CENTROSOMES: They di vi de i nto t wo bef ore mi t osi s. They f or m t he Mi cr ot ubul e Or gani zi ng Center , out of whi ch t he mi t ot i cspi ndl e gr ows, dur i ng mi t osi s.

MI TOSI S:Prophase:Nucl eol i di sappear

Cent r osomes spl i t and each daught er f orms an ast er.Pr omet aphase

The Nucl ear Envel ope breaks down.Mi cr ot ubul es f r om each cent r osome star t i nt er act i ng wi t h t hechr omosomes.Ki net ochore Mi cr ot ubul es f r om t he cent r omere of each chr omosome mat ureand at t ach t o some of t he spi ndl e mi cr otubul es.Met aphase

The Ki netochor e mi cr ot ubul es al i gn t he chr omosomes al ong t he met aphasepl at e.

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The chr omosomes ar e hel d i n pl ace by t he opposed ki netochor es and t hei rassoci at ed mi cr ot ubul es.AnaphaseKi net ochores on each chromosome separat e, al l owi ng each chr omat i d t o bepul l ed towar d the pol es.Anaphase- A: Ki net ochore Mi cr otubul es short en. Si nce t he pl us end oft hese mi cr ot ubul es i s r i ght at t he cent r omer e, t hi s shor t eni ng causest he chromosomes t o be pul l ed t oward the pol es.Anaphase- B: Pol ar Mi cr otubul es el ongate. The pl us end of t he pol armi cr otubul es f ace t he equator t oo, but t hi s el ongat i on somehow ai ds i npul l i ng ( or pushi ng) t he pol es apar t .Ca+2 seems t o pl ay a rol e i n pr omot i ng anaphase. There i s hi gh Ca+2concent r at i on dur i ng anaphase.

Tel ophase:Daught er chr omat i ds r each the pol es.Ki netochore mi cr otubul es di sappear.Nucl ear envel ope r ef orms as nucl ear l ami ns r eassoci at e, condensedchr omat i n expands, and nucl eol i r eappear .I nvol ves dephosphoryl at i on of many pr otei ns.Cyt oki nesi s.

Act i n and Myosi n pi nch t he cel l and f or m a cont r act i l e r i ng.Or ganel l es and cyt opl asm ar e di st r i but ed evenl y.

KI NETOCHORES: Prot ei n masses t hat f orm at t he cent r omeres duri ngmi t osi s, and t o whi ch ki net ochore mi cr otubul es at t ach.

SCLERODERMA: These pat i ent s produce aut o- ant i bodi es t hat r eactspeci f i cal l y wi t h ki net ochor es.

The Ki netochor e Mi cr ot ubul es el ongat e t owar d t he chr omosome! They havet hei r pl us- end f aci ng t he chr omosome, hence they shor t en dur i ngchromosome separat i on.Both Ki netochores must be at t ached f or t he separat i on t o occur . Thi s i sa bi ol ogi cal saf eguar d t o assur e t hat nondi sj unct i on does not occur .CELL FUSI ON EXPERI MENTS: They provi ded evi dence f or act i vators t hatpr omoted mi t osi s and DNA Synt hesi s. Cel l s i n di f f er ent st ages of t hecel l cycl e were f used t ogether t o see what woul d happen.

G1 Cel l + S Cel l : G1 Cel l i mmedi at el y goes i nt o DNA- Synt hesi s. Thi s i s because t he S- Cel l had S- Phase Act i vat or , whi ch promot ed t heG1cel l t o go i nt o S- Phase.G1 Cel l + G2 Cel l : G1 wi l l go thr ough S- Phase as normal unt i l i tr eaches G2, t hen t he two cel l s wi l l go t hr ough mi t osi s t oget her .So, t he G2 cel l wai t s f or t he G1 cel l t o cat ch up wi t h i t .

Thi s suggest s t hat S- Phase Act i vat or present i n t he S- Phase i s nol onger f unct i onal i n t he G2 phase. Thi s i s i mpor t ant - - i t pr event spol ypl oi dy by not al l owi ng cel l s t o synt hesi ze DNA t wi ce!G2 Cel l + S Cel l : Agai n, S- Phase cel l cat ches up t o G2 cel l , t hen t hey

pr oceed t hr ough mi t osi s t ogether . Thi s expt demonst r at ed t hat t hei r was no S- Phase I nhi bi t or i n t he G2cel l , or el se t he S- cel l woul dn' t have compl et ed mi t osi s.

Thus t here must be some ot her expl anat i on f or why t he G2 cel l doesn' tunder go r epl i cat i on i n pr esence of S- Phase Act i vat or .Any I nt er phase Cel l + M- Phase Cel l : The i nt er phase cel l wi l lpr emat ur el y ent er mi t osi s, f r om any st age, r esul t i ng i n an abnor malcel l .

Thi s i s medi at ed by M- Phase Pr omot i ng Fact or ( MPF) , as bel ow.

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DNA- DAMAGE: When G2 cel l s ar e i r r adi ated, t hei r ent r y i nt o M phase i sdel ayed. They don' t ent er mi t osi s unt i l t hei r DNA- r epai r pr ocesses arecompl ete!CELI AC DI SEASE: I nt est i nal di sease resul t s f r om abnor mal i t i es i ni ntes t i nal epi thel i al cel l di vi s i on.

Cel l s nor mal l y di vi de at t he crypt ( basal ) r egi on of t he cel l - - nott he api cal end.For each di vi di ng cel l , one daught er wi l l become an epi t hel i al cel l andmi gr at e t owar d api cal sur f ace, whi l e t he ot her wi l l r emai n a cr yptcel l .I n Cel i ac Di sease, t hi s pr ocess does not occur nor mal l y.M- PHASE PROMOTI NG FACTOR ( MPF) :

Xenopus Oocyt e MPF Level s:Oocyt e: MPF l evel i s l ow, i n order t o f r eeze egg i n pr ophase, and t opr event mi t osi s.Mat ure Newl y Lai d Egg: MPF Level i s hi ghEarl y Embr yo: MPF l evel s al t er nat i vel y hi gh i n M- Phase and l ow i nI nt er phase.

STRUCTURE: I t has t wo subuni t sCYCLI N: The r egul at or y subuni t . I t i s pr oduced at a const ant r at e i nt he cyt opl asm.CDC2: The ki nase subuni t . I t phosphor yl at es t ar get s t o i nduce mi t osi s.CELL DI VI SI ON CYCLE:Pr e- MPF i s an i nact i ve f or m of Cycl i n + CDC2 i s si t t i ng around i ncytopl asm.Act i ve- MPF i s made by a combi nat i on of t wo t hi ngs:Ki nase Cascade f r omsi gnal t r ansducer s modi f i es t he Pr e- MPF i n compl exr eact i ons ( mul t i pl e phosphor yl at i ons) t o act i ve MPF.Cycl i n l evel s accumul at e i n the cyt opl asm, as cycl i n i s cont i nual l ymade i n many cel l t ypes.Mi t osi s i s i nduced by Act i ve MPF, vi a t he cat al yt i c act i vi t y of t hecdc- 2 subuni t .Act i ve MPF al so pr oduces cycl i nases - - cycl i n degr adat i on enzymes t hatl ower t he l evel s of cycl i n.

Thi s i nact i vat es MPF, unt i l cycl i n i s r esynt hesi zed or unt i l i taccumul ates agai n i n t he cytopl asm

MUSCLESARCOMERE COMPONENTS:

Z- Di sk: The uni on of t wo act i n heads.I t demarcat es t he sarcomere.At t he Z- Di sk, t her e i s no myosi n.A- Band: The di st ance of one t hi ck f i l ament , consi st i ng of t wo myosi nf i l ament s.

I - Band: The di st ance f r om t he end of one t hi ck f i l ament t o t hebegi nni ng of t he next t hi ck f i l ament .Dur i ng cont r act i on, t he I - Band becomes shor t er .

The I - Band consi st s ent i r el y of act i n. The I - Band mar ks t he mar gi ns of t wo adj acent sar comer es. Each I - Bandt echni cal l y l i es wi t hi n two sar comer es.H- Zone: The di st ance f r omt he end of one t hi n f i l ament t o the begi nni ngof t he next t hi n f i l ament .Dur i ng cont r act i on, t he H- Zone becomes shor t er.

The H- Zone consi st s ent i r el y of myosi n.

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The H- Zone l i es compl et el y wi t hi n t he sar comere, near t he cent er of t hesar comere.

ACTI N MYOSI N I NTERACTI ON: I n a myof i br i l , i n cross sect i on:

Si x act i ns can i nt eract wi t h each myosi n. Act i ns are i n a hexagonalarr ay.

Three Myosi ns can i nt er act , i n t r i angul ar f ashi on, wi t h each act i n.

SKELETAL MUSCLE CONTRACTI ON: Myosi n pl ays t he r ol e of an ATPase Act i n-Bi ndi ng Mot or Pr ot ei n.

We wi l l st art wi t h myosi n bound to act i n. When Myosi n i s bound toAct i n, ATP i s bound to t he myosi n head.Wi t h ATP bound, Myosi n can t hen det ach f r omt he act i n t hi n f i l ament .Once detached, t he myosi n i s f r ee to hydrol yze t he bound ATP t o ADP +Pi . I t hydr ol yzes the ATP, and t he ADP + Pi r emai n at t ached t o themyosi n head.

The myosi n t hen r eat t aches t o t he t hi n f i l ament .Reat t achment l eads t o t he rel ease of t he Pi gr oup, whi ch i n t ur n

st r engt hens t he i nt er act i on bet ween the act i n and myosi n.Power St r oke: Wi t h the ATP gone, t he myosi n head under goes aconf ormat i onal change, causi ng t he act i n and myosi n t o move r el at i ve t oeach other.

Then t he myosi n head r el eases t he ADP. Then Anot her ATP must bi nd t o t he myosi n, i n or der f or t he myosi n t or el ease f r om t he Act i n t o st ar t anot her cr oss- br i dge.I f t her e i s no mor e ATP, Ri gor Mort i s r esul t s, i n whi ch t he muscl e i sst uck i n t he cont r act i l e st ate, wi t h myosi n bound t o act i n.REGULATI ON OF THE CROSS- BRI DGE CYCLE: Regul at i on i s accor di ng t oi nt r acel l ul ar l evel s of Cal ci um and i s medi ated by Troponi n Compl ex and

Tr opomyosi n.

RELAXED STATE: Tr opomyosi n i s bound t o t he t hi n f i l ament ar ound i t s maj or groove, i nt he absence of cal ci um.

The Tr oponi n Compl ex i s peri odi cal l y bound t o t he t hi n f i l ament sucht hat i t bl ocks t he i nt er act i on bet ween Act i n and Myosi n.CONTRACTED STATECal ci um bi nds t o t he Troponi n Compl ex, causi ng a conf ormat i onal changei n Tr oponi n- C.

Tr oponi n Compl ex ( Tr oponi n pl us t r opomyosi n) r emoves i t sel f f r om t het hi n f i l ament as a resul t , such t hat Myosi n can bi nd.

ORGANI ZATI ON OF MUSCLE:

MUSCLE: A whol e muscl e i s sur r ounded by an epi mysi um membrane.

I t i s composed of a bundl e of f asci cul i .FASCI CULUS: Each f asci cul us i s sur r ounded by a per i mysi ummembrane.I t i s composed of a bundl e of myof i ber s.MYOFI BER ( MUSCLE FI BER) : Each muscl e f i ber i s surr ounded by anendomysi um membrane.I t i s composed of a bundl e of myof i br i l s.I t i s a ver y l ong and t hi n si ngl e muscl e cel l .I t has a sar col emma pl asma membrane, wi t h an endomysi um basementmembr ane beyond t hat .

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MYOFI BRI L: A bundl e of myof i l ament s, st acked neat l y next t o each ot hersuch t hat t he Z- Di sc i s l i ned up.Ever y Thi n f i l ament i n a myof i br i l can i nt er act wi t h 3 t hi ck f i l ament s.Ever y t hi ck f i l ament i n a myof i br i l can i nt er act wi t h 6 t hi n f i l ament s.Each Myof i br i l i s bat hed i n sar copl asm and sur r ounded by a sarcopl asmi creti cul um f romwhence i t get s i t cal ci um suppl y.MYOFI LAMENT: A ver y l ong, cont i nuous ser i es of sar comeres, consi st i ngof act i n and myosi n.

Thi n Fi l ament : Act i n Thi ck Fi l ament : Myosi nI nt ermedi ate Fi l ament : Some muscl e f i bri l s al so have some i nt ermedi atef i l ament s.

SKELETAL MUSCLE CROSS- SECTI ON ( Locat i on of Nucl ei ) : The nucl ei are al lpushed to t he per i pher y, because t he act i n/ myosi n f i ber s t ake up thecent r al part . Compare t hi s t o car di ac muscl e, whose nucl ei are i n t hecent er .

CARDI AC - VS- SMOOTH MUSCLE: Cardi ac muscl e has nucl ei cent r al l y l ocat edand r el at i vel y more cyt opl asm t han smoot h muscl e.

T- TUBULES: They r un i n t he t r i ad, wi t h sar copl asmi c r et i cul um on ei t hersi de, i n bet ween each of t he i ndi vi dual myof i br i l s. They t r ansmi t t heCa+2 depol ar i zat i on f r om t he pl asma membrane t o the SR, whi ch i n t urnt ransmi t s i t t o al l t he f i bers .

Ca+2 r el ease f r om t he SR i ni t i at es t he muscl e cont r act i on.Ca+2 i s pumped back i nto SR t o rest ore rest i ng, by a Ca+2- ATPase.NEUROMUSCULAR J UNCTI ON:

Act i ve Zone: El ect r on- dense ( dark i n EM scan) pat ch of membr ane at t heend of a ner ve, r i ght at t he neur omuscul ar j unct i on.Note t hat vesi cl es ar e f ound r i ght at t he membr ane, whi l e mi t ochondri aare f ound more pr oxi mal , away f r om t he act i ve zone.

J unct i onal Fol d i s r i ght opposi t e t he act i ve zone.Ach Receptors on t he muscl e membrane are hi ghl y concent r at ed r i ght att he ner ve t er mi nal .

MUSCLE DEVELOPMENT:

Mesenchymal cel l s f orm myobl asts.Myobl ast s pr ol i f er ate and f orm myot ubes by f usi ng t oget her , r esul t i ngi n a l ar ge mul t i nucl eat e cel l .So, muscl e becomes mul t i nucl eated by t he f usi ng t ogether of pr i mi t i vemyobl asts.SATELLI TE CELLS: These cel l s l i e squeezed i n- bet ween t he endomysi um

( basement membrane) of a myof i br i l and t he f i bers t hemsel ves.

Devel opment al l y t hey have the same or i gi n as myotubes. They ar emyobl ast s t hat di d not f use wi t h other myobl ast s dur i ng devel opment .FUNCTI ON = Muscl e Repai r . They pr ol i f erat e t o r epai r damaged muscl et i ssue.

They wi l l di vi de t o r egenerat e muscl e, but t he r egenerat i on may bei ncompl et e.

MUSCLE REGENERATI ON:

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When t he muscl e f i ber s are gone, al l t hat i s l ef t i s t he basal l ami naand r et i cul ar f ormat i on of t he endomysi um.

The sat el l i t e cel l s t hen mi grat e i nt o t he empt y endomysi um.Macr ophages come i n t o r emove necr ot i c r emnants ( debr i s)Muscl e regenerat i on may be i ncompl ete ( muscl e at r ophy or weakness) .Fi ber Spl i t t i ng can occur , wher e t he sat el l i t e cel l can gener at esmal l er dupl i cat ed myof i br i l sect i ons f r om one or i gi nal myof i ber .

DUCHENNE MUSCULAR DYSTROPHY: Poor f unct i on and st r uct ure of skel et almuscl e.

Symptoms / Prognosi s:Hyper t r ophy of l at er al t hi gh and cal f , except t hat i t i s not muscl e - -i t i s f at t y t i ssue.Deat h by respi r at or y f ai l ur e, usual l y due t o i nf ect i on and orregurgi t at i on.Esophagus mal f unct i on: The skel etal muscl e port i on of t he esophagu1sdoesn' t f unct i on ri ght , l eadi ng to pr obl ems wi t h swal l owi ng andregurgi t at i on.Upper t hi r d of esophagus: skel et al muscl e

Mi ddl e t hi r d of esophagus: Transi t i on of hal f skel et al and hal f smoot hmuscl e.Lower t hi r d of esophagus: Smoot h muscl e.Gower' s Si gn: Di agnost i c t est of abi l i t y to squat down and st and backup.Hi st opat hol ogy: You see necrot i c muscl e f i ber s, t hat ul t i mat el y f i l lwi t h f at i nf i l t r at es, gi vi ng t he pseudohyper t r ophi c appearance t o t hemuscl e.Pat hol ogy: Faul t y Dystr ophi n Gene, r esul t i ng f ocal l esi ons on t hemuscl e membr ane - - - - - - > Cal ci um l eaks i n t he cel l - - - - - - > per pet ualcont ract i on -- - - - - > necrosi s

You get cont r act ed myof i bers. You get swol l en mi t ochondr i a. The f i bers r emai ni ng ( t hat ar e not necr ot i c) ar e spheroi d.GENETI CS: X- Li nked r ecessi ve di sorder . I t i s passed f r omMother t o Son( hemi zygous) on t he X- chr omosome.DMD Gene, codi ng f or Dyst r ophi n, i s very l arge. Many of t he mutat i onsare new mutat i ons.

Ther e ar e brai n and car di ac i sof or ms of t he Dyst r ophi n prot ei n.Werdni g Hof f man Muscul ar Dyst r ophy: Var i ant wherei n a smal l por t i on oft he dystr ophi n i s mi ssi ng. I n DMD, a l ar ge por t i on i s mi ssi ng.DYSTROPHI N: Funct i on i s t o l i nk t he muscl e f i bers wi t h t heext r acel l ul ar mat r i x. I t f uncti on i n a spectr i n- l i ke f ashi on, t oconnect t he ext r acel l ul ar matr i x wi t h muscl e act i n. Thi s pr ovi desmuscl e membr ane st abi l i t y. Beyond t hat f unct i on i s uncl ear.

TREATMENT METHODS:Sat el l i t e Cel l Repl acement

They t r i ed t o i nj ect donor sat el l i t es t o provi de donor dyst r ophi n, butt he dyst r ophi n coul dn' t get past t he basement membr ane bar r i er t o gett o t he membr ane. Usi ng col l agenase f or t hi s pur pose hel ped but di dn' ti ncr ease muscl e st r engt h.Vi r al I nf ect i on wi t h t he Cor r ect Gene - - sever e l i mi t at i on her e was t hehuge si ze of t he DMD gene.Repai r Poi nt Mutat i ons on mRNA - - Novel approach wher e they repai r t hemRNA t o get past t he st op codon poi nt , suppl i ng an art i f i ci al ami noaci d at t hat poi nt .

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I n- Vi t r o Screeni ng: Ext r act cel l s f r om t he embr yo and t est f or apar t i cul ar exon on t he DMD geneI f t he embryo had t he DMD gene, t hen a posi t i ve PCR product woul d beobt ai ned ( i . e. some of t he exons wer e not t her e) .I f t he embryo di d not have t he DMD gene, t hen a negat i ve PCR productwas obt ai ned, and t hey coul d r ei mpl ant t he embryo f or devel opment .PENNI FORM MUSCLE: Muscl es wi t h a centr al t endon, used f or st r ength andst abi l i t y. Exampl e = Transver sus Abdomi ni s.

FUSI FORM MUSCLE: Muscl es wi t h a t endon on ei t her s i de l ongi t udi nal l y,used f or speed. Exampl e = Bi ceps Br achi i .

Ways of Di st i ngui shi ng CARDI AC MUSCLE - vs- Smoot h Muscl e:Cr oss- Sect i on: Cardi ac Muscl e has a cent r al l y pl aced nucl eus, wher east he nucl eus i s around the per i pher y i n skel et al muscl e.Longi t udi nal Sect i on: Car di ac muscl e appear s st r i at ed, but wi t hbr anches.

The car di ac cel l s ar e branched i n l ongi t udi nal sect i on. The car di ac cel l s have t he same st r uct ural uni t s as skel et al muscl e,al t hough SR and T- Tubul es won' t be as r egul ar .

I n Cardi ac Cel l s you get a di ad i nst ead of a t r i ad - - one SR membr anewi l l adher e wi t h one T- Tubul e.I NTERCALATED DI SK: The j unct i onal compl ex t hat separat es cardi ac muscl ecel l s. They al ways coi nci de wi t h t he Z- Li ne of muscl e f i ber s.

Fasci a Adher ens i s t he basi c st r uct ur al connect i ons bet ween the twocel l s.

They ar e si mi l ar t o desmosomes but ar e onl y f ound i n car di ac cel l s. The Fasci a Adher ens appar ent l y bi nds t hi n f i l aments i n adj acent I - bandst o t he pl asma membr ane of cardi ac cel l s.Desmosomes: The t i ght est poi nt of connect i on between t wo car di ac cel l s.Gap J unct i ons: Al l ows f ast el ect r i cal conduct i on bet ween two car di accel l s.CARDI AC I SCHEMI A:

St r uct ur al changes i n i schemi a:15 mi nut es: St r uct ure changes occur.30- 60 mi nut es: The cel l can st i l l r ecover .> 60 mi nut es: The cel l di es, necr osi s.Reperf usi on I nj ur y: Occur s when oxygen i s suddenl y r epl eni shed af t erextended depr i vat i on. I t can cause mi t ochondr i a t o swel l up andexpl ode.Hi st opat hol ogy of Car di ac I schemi a:Chromat i n i s more condensed t han normal .Mi t ochondr i a swel lGl ycogen st ores are absent .Unl i ke skel et al muscl e, car di ac muscl e cannot r egenerat e.

SMOOTH MUSCLE:

Hi stol ogi cal Charact er i st i csSi ngl e cent r al nucl eus, but t he amount of cytopl asm i s l ess as comparedt o car di ac muscl e, i . e. t he nucl eus t akes up a gr eat space i n t he cel li n smoot h muscl e.Cel l i s not st r i at ed, as act i n and myosi n ar e not ar r anged i n l i nearf ashi on.

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The amount of act i n i s great er t han t hat of myosi n. Act i n i s bound t odense bodi es i n t he cyt opl asm, whi ch are hel d i n pl ace by i nt ermedi atef i l ament s.CONTRACTI ON:RELAXED STATE:Myosi n t hi ck f i l ament s ar e spar se, i . e. t hey ar e not pol ymer i zed.Myosi n i s dephosphoryl at ed when r el axed.CONTRACTED STATE:Myosi n Li ght Chai n i s phosphoryl ated.Myosi n f orms more thi ck f i l ament s

Thi s al l ows t he dense bodi es t o move t owar d each ot her .PROCESS OF CONTRACTI ON / REGULATI ONCal ci um act i vat es Cal modul i n Compl ex.Cal modul i n Compl ex then act i vat es t he Myosi n Li ght Chai n Ki nase (MLCK) .Myosi n Li ght Chai n Ki nase t hen phosphoryl ates t he myosi n l i ght chai nsDOWN- REGULATI ON: Here are ways of i nduci ng r el axat i on or l esseni ngcont ract i l e t oni ci t y.bet a- Adr ener gi c t r ansduct i on can phosphoryl ate t he Li ght Chai n Ki nase,t hus deact i vat i ng i t - - - - - - > No Phosphor yl at i on of Myosi n Li ght chai ns- - - - - - > Less cont ract i on.

Phosphatases r emove t he phosphate f r om t he myosi n l i ght chai n to i nducerel axat i on.ACTI N- BASED MOTI LI TY:

Pseudopod Movement : Cyt opl asmi c st r eami ng as medi at ed by act i npol ymer i zat i on and depol ymer i zat i on. No myosi n i s i nvol ved.Cytoki nesi s: Once agai n i nvol ves i nt er act i on of act i n and myosi n t opi nch t he cel l .MI CROTUBULE BASED MOTI LI TY: Dynei n and Ki nesi n

Dynei n i s a mi nus- end pr ot ei n. I t t r avel s f r om pl us t o mi nus and t husai ds i n r et r ogr ade axonal t r anspor t .Ki nesi n i s a pl us- end pr ot ei n. I t t r avel s f r om mi nus t o pl us and t husai ds i n ant er ogr ade axonal t r anspor t .

CONNECTI VE TI SSUECOMPONENTS OF CONNECTI VE TI SSUE:Fi ber sCol l agensEl asti c Fi bersGr ound Subst ance ( Proteogl ycans)Cel l sMacr ophagesMast Cel l sFi br obl ast sCOLLAGEN: The pr i mary f i ber f ound i n connect i ve t i ssue. Al t hough ot herel ast i c f i ber s ar e al so f ound.

Tr opocol l agen i s t he basi c st r uct ural uni t , consi st i ng of t hree al pha-chai ns ar r anged i n a hel i x.

Tr opocol l agen shows a t ypi cal bandi ng pat t er n on EM, due t o t hest agger ed hel i ces. Procol l agen doesn' t show t he bandi ng pat t er n.Chemi st r y:Ever y thi r d r esi due i s gl yci ne.Hydr oxypr ol i ne and Hydr oxyl ysi ne ar e al so pr eval ent .Synt hesi s:

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Regi st r at i on Pept i de: The r egi st r at i on pept i de, di st i nct f r om t hesi gnal pept i de, accompl i shes t wo t hi ngs.I t keeps t he col l agen hel i x sol ubl e i n t he cel l .I t al l ows t he al pha- st r ands t o al i gn pr oper l y i n t he cel l , i n or der t of orm t he hel i x.al pha- st r ands are synt hesi zed i n the ER as usual . The si gnal pept i de i scl eaved but t he regi st r at i on pept i de, as above, r emai ns.Post - Tr ansl at i on Modi f i cat i ons:Lysyl Hydr oxyl ase and Prol yl Hydr oxyl ase hydr oxyl ate l ysi ne and pr ol i ner esi dues.Var i ous gl ycosyl at i ons are done.Pr ocol l agen i s f or med i nt r acel l ul ar l y. I t i s t he sol ubl e, spont aneousl yf or med hel i x that r esul t s f r om t he i ndi vi dual st r ands, af t er post -t r ansl at i on modi f i cat i ons ar e made:Pr ocol l agen st i l l has the r egi st r at i on pept i des i nt act.Pr ocol l agen i s secret ed.Pr ocol l agen Pept i dases t hen cl eave t he regi st r ati on pept i deext r acel l ul ar l y, t o resul t i n Tropocol l agen.

Tr opocol l agen t hen f or ms f i br i l s spont aneousl y, st abi l i zed by cr oss -l i nks.

Lysyl Oxi dase t ur ns on Hydr o l ysi ne r esi dues i nt o al dehydes, t ostabi l i ze cross- l i nk f ormat i on.Fi bers f orm by t he associ at i on of f i br i l s .Col l agen Types:Col l agen I : Ski n + BoneCol l agen I I : Cart i l ageCol l agen I I I : Aort a ( Ret i cul ar Fi bers)

These ar e al so associ at ed wi t h el ast i c f i bersA si l ver st ai n wi l l onl y st ai n r et i cul ar f i ber s, so t hey can bei dent i f i ed.Col l agen I V: Basement MembraneBasement membr anes r etai n the r egi st r at i on pept i de.As a resul t t hey don' t f or m f i ber s but i nst ead f or m sheet s.COLLAGENASE: Br eakdown of Col l agenProcess of Col l agen Degr adat i on:Col l agenase i s secr eted as a pr oenzyme and i s act i vat ed by otherpr ot eases.I t cl eaves at a speci f i c si t e - - about 25% of t he way down t hemol ecul e.

The speci f i c cl eavage r esul t s i n t he spont aneous denat urat i on of t hecol l agen hel i x. The smal l er pi eces have a l ower mel t i ng poi nt and aremor e vol at i l e.Ot her pr ot eases t hen f i ni sh of f t he j ob.Col l agenase act i vi t y i s t emper at ur e and f l ui d- dependant

REGULATI ON of COLLAGENASE: Ti ssue I nhi bi t or s of Met al l oprot eases ( TI MPs) : They bi nd onl y t o

act i vat ed col l agenases, t hus moder at i ng t hei r act i vi t y through negati vef eedback.Ext r acel l ul ar Pr ot eases: Thr ee t ypes of ext r acel l ul ar pr ot eases ai d i nt he degr adat i on of col l agen:Met al l opr oteases. Col l agenase i s a met al l opr oteaseSer i ne Pr oteases. For exampl e - - el ast ase and t hr ombi nCat hepsi ns.

Col l agen- r el at ed di sor der sEhl er s- Danl os Syndr omes: Hyper extensi bi l i t y of ski n and j oi nt s.

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Ost eogenesi s I mperf ectaRecessi ve Dyst r ophi c Epi der mol ysi s Bul l osa: Too much col l agenase.Scur vy: Vi t ami n- C def i ci ency l eads t o mal f unct i oni ng pr ol ylhydr oxyl ase.

ELASTI C FI BERS:

Ar r angement s of el asti c f i ber s: They can be ar r anged i n t hr ee di f f er entwaysFi ber s / Fi ber Bundl es - - as i n ski nLamel l ae ( sheet s) - - as i n vascul at ur eFi ne Net works - - as i n t he l ungPr ot ei n Composi t i on:Mi crof i br i l l ar Pr ot ei n: For ms t he under l yi ng "scaf f ol di ng" over whi chthe el as t i n i s l ai d.El ast i n: The amor phous, el ast i c mat er i al .El ast i n i s resi st ant t o degr adat i on, except by el ast ase.Desmosi ne and I sodesmosi ne: Cr oss- l i nk el ast i n, f ormi ng a net work, andst abi l i zi ng t he el ast i n dur i ng st r et chi ng and compr essi ng.Synt hesi s:

Fi rst , mi crof i br i l l ar protei n l ays down t he scaf f ol di ng. Then, el ast i ns get l ai d down on t op.AGI NG: Wr i nkl es occur as mi crof i br i l l ar st r uct ur e i s l ostEmphysema: Loss of el ast i ci t y i n l ung. Rar e f or m = congeni t almal f unct i on of el ast ase i n l ung.GROUND SUBSTANCE: Pr ot eogl ycans. They consi st s of a core pr ot ei n +Gl ucosami nogl ycans

Gl ycosami nogl ycans ( GAGs) : Li near pol ymers of r epeat i ng di sacchar i desof hexosami ne pl us a ur oni c aci d such as gl ucur oni c aci d.GAG- r esi dues ar e of t en sul f ated.SI GNALI NG FUNCTI ON:GAGs have a hi gh negat i ve char ge and are hi ghl y hydr ophi l i c.Basi c Fi br obl ast Gr owt h Fact or ( BFGF) can bi nd t o pr oteogl ycans t opr omot e the gr owt h of f i br obl ast s.I n t hi s capaci t y pr ot eogl ycans al so act as a si eve cont r ol l i ng passageof mat er i al s t hr ough t he ECM. Thi s pr oper t y i s especi al l y i mport ant i nt he ki dney.Aggr ecan: Found i n Hyal i ne Cart i l age.Per l ecan: Found i n Basement MembraneSyndecan: Found i n Epi t hel i al Ti ssue. I t r emai ns at t ached t o t he pl asmamembr ane.Hyal ur oni c Aci d: Not associ at ed wi t h a cor e pr ot ei n i t sel f , but ot herpr ot eogl ycans can associ at e wi t h i t .

Ti ssue Di st r i but i on:Vi t r eous humor of eye.Synovi al Fl ui d of j oi nt s.

I t f aci l i t at es cel l mi gr at i on dur i ng gr owt h and r epai r .Hyal ur oni dase i s secr et ed when hyal ur oni c aci d i s no l onger needed.BASEMENT MEMBRANES: Made of t he Basal Lami na + Ret i cul ar Lami na, or t wol ayer s of basal l ami na. I t i s vi si bl e at t he l i ght mi croscope l evel ,whi l e basal l ami na by i t sel f i s not .

Basal Lami na: I t pr ovi des a subst r at e f or epi t hel i al cel l s. I t consi st sof di f f er ent component s:

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Lami na Rara: Pr i mary const i t uent of t he basal l ami na, composed of t wopr ot ei ns - - l ami ni n and f i br onecti n. I t i s di r ectl y adj acent t o t heepi thel i al cel l s.I t i s el ect r on l ucent i n t he el ect r onmi croscope.Lami ni n: Ver y l ar ge pr ot ei n i t t hr ee chai ns. Ther e ar e speci f i c bi ndi ngdomai ns f or col l agen and hepari n.Ent act i n i s of t en associ at ed wi t h Lami ni n.CANCER: Lami ni n wi l l hook t o i nt egr i n recept or s. I n addi t i on i t mayhave i t s own r ecept or, whi ch act s i n t umor met ast asi s.Fi br onect i n: Two chai ns. I t i s i mpor t ant f or wound heal i ng and cel lmi gr at i on.

Ther e ar e t hree f or ms of f i bronect i n:Pl asma Fi br onect i n: Bi nds f i br i n and f i br i nogen, and pl ays a r ol e i nbl ood cl ot s.Cel l Sur f ace Fi br onect i nMat r i x Fi bronecti n - - i nsol ubl e mat r i x f i br i l s .Agai n, i t has speci f i c bi ndi ng domai ns f or hepari n and col l agen, and i twi l l hook i nt o cel l ul ar i nt egri n recept ors.Lami na Densa: The next l ayer , under neat h the Lami na Rara. Composedmai nl y of Col l agen I V ( basement membrane col l agen) and Hepar i n.

I t i s el ect r on- dense i n t he EM mi croscope.Agai n, Col l agen I V sti l l has i t s gl obul ar r egi str at i on pept i de, so i tf orms meshworks i nst ead of f i ber s.Hepar i n Sul f at e i nt er acts el ectr ost at i cal l y wi t h t he Col l agen I V.Lami na Ret i cul ari s: The next l ayer down. Composed of Col l agen I I I andCol l agen VI I . Thi s makes up t he Ret i cul ar ( el ast i c) f i ber s i n somebasement membr anes.Col l agen I I I i s the mai n r et i cul ar col l agen.Col l agen VI I act s as an anchor , t o hol d t he r et i cul ar f i ber s t o t hebasal l ami na.FNXN: The ret i cul ar l ami na connect s t he basal l ami na t o t he under l yi ngst r oma.Basement Membr ane: The ver y bot t om l ayer of t he epi t hel i al l ayer .I nt egri ns: Epi t hel i al Cel l ul ar recept ors t hat al l ow t he cel l s t oi nteract wi t h t he basement membrane.STRUCTURE: I ntegr al membrane heterodi mer i c prot ei ns, wi t h al pha andbet a subuni t s non- coval ent l y l i nked.Li gand- bi ndi ng Domai n: Bi nds t o a speci f i c sequence on l ami ni n andf i br onecti n i n t he ext r acel l ul ar mat r i x.

The speci f i c sequence i s Ar g- Gl y- Asp ( RGD)I nt r acel l ul ar At t achment : The pr ot ei n i s at t ached t o the act i ncyt oskel et on, vi a the f ol l owi ng anchor pr ot ei ns:

Tal i nVi ncul i nal pha- Acti ni nFUNCTI ON: I nt egr i ns medi ate cel l ul ar adhesi on and mi gr at i on t hrough t heECM.

LEUKOCYTE MI GRATI ON: Par t of t he i nf l ammat or y response.

Sel ect i ns: Speci al i zed gl ycopr ot ei ns on endot hel i al cel l s, t hat servet o at t r act l eucocyt es t o that l ocat i on when act i vat ed.

They al l ow f or st r onger i nt er act i on of t he ECM wi t h t he l eucocyt ei nt egr i ns .C: el l Adhesi on Mol ecul es ( CAMs) Af t er bei ng at t r act ed by sel ect i ns, t hel eucocyt es i nt er act wi t h CAMs on t he endot hel i al sur f ace.

The l eucocyt es bi nds t o t he endot hel i al cel l CAMs.

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Act i vat ed l eucocyt es must t hen secrete pr ot eases and col l agenases t omi gr at e t hr ough t he vessel wal l and go t o t he si t e of i nf ect i on.

WOUND HEALI NG:Pl asma Fi br onect i n bi nds t o t he bl ood cl ot , t hus causi ng Pl at el etDer i ved Gr owt h Fact or t o be rel eased by the pl atel et s.PDGF, al ong wi t h C5a, t hen at t r act neut r ophi l s and macrophages.Macrophages then secrete pr ot eol yt i c enzymes f or f i brobl ast s and smoot hmuscl e cel l s, so t hey can get t hr ough t he debr i s.

Then t he mat r i x i s r est or ed by f i brobl ast s, t hen t he endot hel i al cel l sar e rest or ed.

TUMOR METASTASI S: Some t umor cel l s secr et e col l agenase, t hus breaki ngdown basement membranes and al l owi ng t he met ast at i c cel l s t o penet r at et he bl ood vessel s.FI BROBLASTS: RESI DENT (al ways present ) Connect i ve t i ssue cel l s t hatsynt hesi ze col l agen, el ast i n, and basal l ami na.Fi br obl ast s ar e not t he onl y cel l s t hat synt hesi ze t hi s stuf f .Epi t hel i al t i ssues and smoot h muscl e cel l s can make thei r own ECM, t oo!Hi st ol ogy:

They have l i t t l e cyt opl asm and l ot s of ER and Gol gi , whi ch i s what we' d

expect f or t hei r synt het i c rol es.Fi br obl ast Act i vat i ng Fact or up regul at es ECM pr oduct i on i nf i brobl as ts .Lymphocyt es and monocyt es can secr et e f i br obl ast act i vat i ng f actort oward thi s end.

ADI POCYTES: A RESI DENT CELL i n connect i ve t i ssue - - i . e. i t i s al wayspr esent .

Whi t e Adi pose Ti ssue: Ef f i ci ent , l ow- densi t y st or age f or m f or ener gy.I t i s hi ghl y vascul ar i zed and i nner vat ed.HI STOLOGY: Bi g l i pi d dr opl et wi t h nucl eus pl us mi ni mal cytopl asmi ccomponent s al l of f t o one si de.Li pi d Deposi t i on ( Anabol i c) : Li popr ot ei n Li pase f r ees t wo of t he t hr eef at s f r om t r i acyl gl ycer ol s f r om chyl omi crons i n t he bl ood.

The l i popr ot ei n l i pase i s l ocat ed i n t he vascul ar endot hel i um. The r emai ni ng monoacyl gl ycer ol st ays i n t he bl ood and goes back t ol i ver .

The t wo f r eed f at t y aci ds di f f use t hrough t he capi l l ar y endot hel i um - - -- - - > basal l ami na - - - - - - > connect i ve t i ssue - - - - - - > adi pose basall ami na - - - - - - > adi pocyt e - - - - - - > and i nt o t he adi pose t i ssue.Li pi d Mobi l i zat i on ( Cat abol i c) : Hor mone Sensi t i ve Li pase i s act i vat edvi a the bet a- adr ener gi c pat hway. I t f r ees f at t y aci ds f r omt r i acyl gl ycer ol s i n t he adi pose t i ssue.bet a- Adrenergi c Pat hway means that Hormone Sensi t i ve Li pase i sphosphor yl at ed t o be act i vat ed ( vi a cAMP - - - - - - > Pr otei n Ki nase, et c. )Br own Adi pose Ti ssue: Speci al i zed f or t her moregul at i on.

I t i s present i n hi bernat i ng and newborn humans, but not i n humanadul t s.Uncoupl i ng Prot ei n uncoupl es t he oxi dat i on of Acet yl - CoA i n adi pocyt emi t ochondr i a, such that no ATP i s produced. I nst ead, t he gener atedel ect r ochemi cal gr adi ent i s di ssi pat ed as heat .OBESI TY:Hyper pl asi a of adi pocyt es occur s af t er bi r t h, but t he adul t doesn' tgai n or l ose adi pocyt es appr eci abl y. Obesi t y occur s by hyper t r ophy ofadi pocyt es.Body Mass I ndex = ( Wei ght ( kg) ) / ( Hei ght ( m) ) 2

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Heal t hy BMI i s 23- 28. Two f or ms of obesi t y:Andr oi d Obesi t y, wei ght i n upper body and abdomen, i s cor r el at ed wi t hr i sks f or CHD.Gynecoi d Obesi t y, wei ght i n hi ps and t hi ghs, i s not cor r el at ed wi t hr i sks f or CHD."Reduced Obese" : When an i ndi vi dual gai ns wei ght and then l oses i tagai n, sever al t hi ngs change physi ol ogi cal l y whi ch make i t di f f i cul t t okeep of f t he wei ght :Met abol i c needs go down f r om t he or i gi nal basel i ne l evel - - i . e. t ot aldai l y cal or i c r equi r ement s go down af t er havi ng l ost wei ght .Upr egul at i on of adr enor ecept or s occur s - - maki ng i t easi er t o mobi l i zef at t y aci ds f r om adi pose t i ssue ( t hat i s act ual l y good news) .BUT, t here i s a decr eased r esponse t o hypogl ycemi a - - cat echol ami nesar en' t r el eased as r eadi l y.LEPTI N: A pr otei n made by adi pocyt es t hat cor r el ates wi t h obesi t y i nl aborat ory mi ceEXPTs i n mi ce suggested that obesi t y mi ght be due to a l ack of l ept i n.Mi ce that were obese had no l ept i n.Unf or t unat el y t hi s di d not hol d the same f or humans. Obese humans

act ual l y had mor e l ept i n, so ther e was a posi t i ve cor r el at i on. Ther e appears t o be Lept i n r ecept or s i n t he hypot hal amus, whi ch wi l l bei nvol ved wi t h hunger r egul at i on.

They have al so f ound l ept i n r ecept or s i n t he chor oi d pl exus ofvent r i cl es .ADI PSI N: I t f orms Acyl - St i mul at i ng Pr otei n ( ASP) whi ch gener al l ypr omot es the bui l di ng of t r i acyl gl ycer ol s.Many obese pat i ent s have el evated adi psi n l evel s, meani ng that t hey canmake f ats r eadi l y but t hey have normal or subnormal r ates of mobi l i zi ngt hem.

Tumor Necr osi s Fact or : Obese pat i ents al so seem t o have el evat ed l evel sof t hi s f actor. Thi s i s r el at ed t o devel opment of i nsul i n r esi st ance.MAST CELLS: TRANSI ENT Connect i ve Ti ssue Cel l . They f unct i on i n al l ergi cr eacti ons.

They r espond t o I gE f r om pl asma cel l s.Hi st ol ogy:

They char act er i st i cal l y have cyt opl asm f ul l of dark- st ai ni ng granul es.Mast Cel l Gr anul es ar e r el eased i n an al l er gi c r eact i on. They cont ai n:Hepari n, an ant i coagul ant .Hi st ami ne, vasodi l ates smal l vessel s, causi ng i ncreased mi croper f usi onof t he t i ssue ( i . e. r edness)Ser otoni nLeukot r i enesMACROPHAGES: TRANSI ENT Connect i ve Ti ssue Cel l . They ar e der i ved f r ommonocytes ci r cul at i ng i n t he bl ood.Phagocyt osi s i s of t en medi at ed by I gG

Hi st ol ogy:Can be di st i ngui shed f r om ot her t r ansi ent cel l s because t hey usual l yhave f or ei gn mat er i al s i ngest ed.

They have numer ous smal l l i pi d dropl et s ( vacuol es)PLASMA CELLS: TRANSI ENT Connect i ve Ti ssue Cel l . They secreteant i bodi es.

Mor phol ogy / Hi st ol ogy: They have a cl ock- f ace nucl eus. They have a per i nucl ear cl ear ar ea.

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Ø

EMBRYOLOGY

v Ger m l ayer Subdi vi si on Der i vat i vesEpi der mi s- - - - - - - - - - - - - - - -Ski n gl ands, hai r , nai l sNasal epi t hel i umEct oder m Sur f ace Or al epi t hel i um and t oot h enamelAdenohypophysi sLens of eye, corneaI nner earNeur al t ube Br ai n: neur ohypophysi s, cr ani al mot or ner ves, epi physi s,opt i c ner ve and r et i naSpi nal cor d: spi nal mot or ner vesCr ani al crest der i vat i ves: sensor y gangl i a, par asympat het i c gangl i a,

gl i al and Schwann cel l s, l ept omi ni nges, mel anocyt es, car ot i d body andpar af ol l i cul ar cel l s, many bones of f ace and cr ani um, vi scer alcar t i l ages ( t hr oat ) , connect i ve t i ssue, mi nor muscl es, car ot i d body,odont obl ast s, t hyr oi d, par at hyr oi d, t hymus, sal i var y and l acri malgl ands, out f l ow t r act of hear t , car di ac semi l unar val ves, wal l s ofaor t a and aor t i c ar ch der i ved ar t er i es, ci l i ar y muscl es, car t i l age ofexter nal earNeur al cr est Trunk cr est der i vat i ves: spi nal gangl i a, par asympat het i cgangl i a, par asympat het i c gangl i a, sat el l i t e and Schwann cel l s,mel anocyt es, adr enal medul l a- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Mesoder m- - - - - - - - -Somi t es( Par axi al ) Connect i ve t i ssue of ski nSkel et al muscl esAxi al skel et onI nt ermedi ate Ki dneysGeni t al st r uct ur esRenal and geni t al duct sLat er al Somat i c: connect i ve t i ssue of vent r al body wal l , par i et alper i t oneum, bl ood vessel s, l i mbsSpl anchni c: adr enal cor t ex, vi scer al per i t oneum, heart , bl ood vessel s- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - -

Endoder m- - - - - - - - - -

Di gest i ve t ubeRespi r at or y epi t hel i umDi gest i ve gl andsPharyngeal gl andsEust achean t ube and l i ni ng of mi ddl e earUr i nary bl adderHI GHLI GHTS OF THE EMBRYONI C PERI OD: ( WEEKS 3- 8)

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Uni l ateral r enal agenesi s wi l l cause the ot her ki dney t o become muchl ar ger , whi l e bi l at er al agenesi s wi l l l ead t o ol i gohydr amni os. Thei ncr eased pr essure and decr eased vol ume of amni ot i c f l ui d i n t hepl acent a wi l l cause Pot t er ’ s f ascae, and pul monar y hypopl asi a.

Ear l y bi f ur cat i on of t he ur et er i c bud wi l l cause bi f ed ur et er , whi l el at e bi f ur cat i on wi l l cause bi f ed pel ves i nt o a si ngl e ki dney. An ext r aur et er i c bud wi l l l ead t o a super numer ary ki dney or a l arge, f usedki dney.

Ect opi c ur et er s i n t he bl adder open al ong t he edge of t he t r i goner egi on. They can somet i mes open i nt o t he vagi na or uret hr a, causi ngi ncont i nence. The ur et er f eedi ng the super i or ki dney ent er s i nt o thei nf er i or , ect opi c pos i t i on.

Mul t i cyst i c ki dneys l ead t o i ncompl et e devel opment of cal yxes andpr i mi t i ve duct al devel opment . Pol ycyst i c ki dneys ar e caused by ar ecessi ve genet i c di sor der , l eadi ng t o pr obl ems wi t h di f f er et i at i on ofr enal cel l s, not pr obl ems wi t h col l ect i ng por t i ons of t he ki dney.

A horseshoe ki dney i s caused by pr obl ems wi t h ascensi on and rot at i on oft he ki dney. I t r esul t s i n a l ar ge, f used ki dney pr esent i n t he pel vi s.I t ’ s ascent can by bl ocked by t he i nf er i or mesent er i c ar t er y, l eadi ngt o pr obl ems. Fai l ur e to ascend can al so l ead t o ecot opi c ki dney,pr esent i n t he pel vi s. Usual l y thi s causes no pr obl ems.

The r enal bl ood suppl y ascends al ong wi t h t he ki dney, and new ar t er i esare cr eat ed as ol der ones more caudal l y ar e r eabsorbed. I n t he case ofa pel vi c or hor seshoe ki dney, ar t er i es wi l l ar i se f r om t he l ower par tof t he aor t a.

Ur eterocoel e occur s when ectoderm f r om t he UG si nus overgr ows andoccl udes t he ur et er i c openi ng. Thi s t ends t o occur af t er t hemesonephr i c duct s have been absor bed i nt o t he bl adder , cr eat i ng t het r i gone regi on, whi ch i s made f r om i nt er medi ate mesoder m. The rest oft he bl adder i s made f r omspl anchni c mesoder m, and the ent i r e t hi ng i sl i ned wi t h endoderm. When thi s endoderm overgr ows t he ur eteri c openi ngsur et er ocoel e occur s. Post er i or ur et hr al val ves occur when mucosal f l apsoccl ude the ur et hr a near where t he vas ent ers, causi ng occl usi on.

The bl adder f or ms f r om t he cl oaca af t er i s part i t i oned by t he uror ect alsept um, and i s made f r om spl anchni c mesoderm. The t r i gone comes f r omt he absor pt i on of t he mesonephr i c duct s by the bl adder .

The urachus i s t he r emnant of t he al l ant oi s, and connect s t he bl addert o t he umbi l i cus. I t becomes t he medi an umbi l i cal l i gament , but i f i t

r emai ns pat ent i t can cause cyst s, f i st ul a, and si nuses.

Extr ophy of t he bl adder i s caused by a def ect i n t he vent r al wal l ,exposi ng the t r i gone port i on of t he bl adder . I t i s caused by non-cl osur e of t he umbi l i cus due to a def ect i n mesoder mal mi gr at i on. I t i sassoci ated wi t h epi spadi as because t he dorsal surf ace of t he peni s doesnot f or m pr oper l y.

Li mb Devel opment Quest i ons

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A l i mb bud i s an i ni t i al out gr owt h f r omt he embr oni c f l anks, i nduced byFGF- 10. Later , t he api cal ect oder mal r i dge takes over , pr omot i ng gr owt hby rel easi ng FGF- 8 and l ater a number of FGF f act ors mai ntai ni ng t hel i mb bud.

The zone of pol ar i zi ng act i vi t y i s present i n t he post er i or mesoder m,and causes the di f f er ent i al gr owt h of t he l i mb bud i n t heant er i or / post er i or pl ane by r el easi ng soni c hedgehog (Shh) pr otei n. Shhi s mai nt ai n by FGF f r omt he AER. Thi s causes di f f er ences i n expr essi onof var i ous HOX genes, shi f t i ng t hei r “st r i pes” f r om pr oxi mal / di st al t oa post er i or / ant er i or di r ect i on. I have no i dea what t he hel l Ri ndl er i st al ki ng about her e.

A chi l d wi t h mi r r or - i mage devel opment of t he f oot coul d be expl ai ned byt he presence of t wo ZPA’ s ( ??) , or poss i bl y a ZPA t hat was somehowshi f t ed t o a dorsal / vent ral axi s ( ??) .

The i nnver vat i on pat t er n of t he dermat omes r ef l ect s t he or i gi n andgr owt h of t he l i mb buds i n t hat t hey show a rot at i on pat t er n.

Basi cal l y, t he i nduct i on of t he l i mb ( whose bones come f r om l ateralmesoder m, and muscl es f r om myot omes) i s done by FGF- 10, f ol l owed by P/ Dgrwot h mai ntai ned by t he AER r el easi ng FGF- 8 and ot her FGF’ s. P/ Ddi f f er ent i at i on occur s as a r esul t of t he cl ock mechani sm of t hepr ogr ess zone and i t ’ s r el ease of Msx ( onl y f ound i n t he pr ogr esszone) . A/ P di f f er ent i at on occur s because of Shh rel eased f r om t he ZPA,whi ch causes st uf f t o happen wi t h HOX genes. D/ V di f f er ent i at i onr esul t s f r omt he ef f ect s of WNT7a pr oduced by t he dorsal ect oder m andEngrai l ed- 1 produced by t he ventr al ect oderm. Dorsal mesenchyme creat esLMX1b, and l eads t o t he f ormat i on of t he nai l s and patel l a.

Hi ndgut Quest i ons

The hi ndgut gi ves r i se t o t he di st al ½ of t he t r ansver se col on( I nt r aper i t oneal ) , t he descendi ng col on ( Ret r oper i t oneal ) , si gmoi dcol on ( I ) , r ectum( R) , and anal canal ( R) .

The pect i nate l i ne i s i mport ant because i t i s t he di vi di ng poi ntbetween endoderm ( f r om t he f ormer cl oaca) and ect oderm, causes abr uptchanges i n NV suppl y and types of muscl e. The vascul ar suppl y changesf r om I MA t o t he i nf er i or r ect al ar t er i es, t he i nner vat on changes f r omaut onomi c ( vi a symps f r oml umbar spl anchni c ner ve, i nf er i or mesent eri c

gangl i on, super i or hypogast r i c pl exus, i nf er i or hypogast r i c pl exus,par asym f r om pel vi c spl anchni cs t o i nf er i or mesent er i c pl exus t osynapse i n t he r ect al wal l ) t o somat i c ( vi a t he i nf er i or r ect al br anchof t he pudendal nerve) . Lymphat i c drai nage changes f r omt he I MA l umbarnodes t o i ngui nal .

Abnormal i t i es of hi ndgut f or mat i on:

Fai l ure of t he Rat hke f ol ds causes t he UR septumnear t he anal membranet o r emai n open, f or mi ng a f i st ul a. I n mal es, a r ect opr ost at i c ur et hr a

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f i st ul a f or ms, whi l e i n f emal es a r ectocl oacal f i st ul a can r esul t .Rectovagi nal or anovest i bul ar f i st ul a can al so r esul t . Basi cal l y, t hef i st ul a wi l l occur somewhere near t he anal membrane.

Fai l ur e of both t he Rathke f ol ds and t he UR sept um l eads t o ar ect ovesi cal sept um i n mal es ( because ther e i s no sept um, t he rect umwi l l j oi n wi t h t he bl adder , whi ch i s f or med f r om t he cl oaca) and i nf emal es, pai r ed vagi nas can r esul t .

Mal al i gnment of t he f ol ds l eads t o r ect opr ostat i c ur et hr a i n mal es, j ust as i n t he f ai l ure of t he Rat hke f ol ds, but al so causes peni l eur et hr al st enosi s, and i n f emal es causes a rect ovagi nal f i st ul a.

I mper f orat e anus occurs when t he anal membrane does not r upt ure. Analstenosi s occur s i f i t part i al l y r upt ur es.

Ot her t ypes of abnormal i t i es i ncl ude l ow and hi gh def ect s. Low def ect si ncl ude pr obl ems wi t h t he pr otocdeum and anal membr ane. I mperf . anus i nan exampl e, as i n anal agenesi s, i n whi ch t her e i s no t he anus. I f af i st ul a i s pr esent , i t empt i es i nt o t he ur et hr a, whi l e i f t her e i s no

f i st ul a t he r ect um ends bl i ndl y. The anus can al so be cover ed bygeni t al f ol ds i n what i s known as “cover ed anus”.

Hi gh anor ect al def ect s – i n anor ect al agenesi s, t her e i s no rectum,anal canal , or anus, and f i st ul as f or m i nt o the ur et hr a or vagi na. Mai ndi f f er ence wi t h r ect al def ect s i s t hat t her e i s no anus what soever . I nr ect al at r esi a, l ack of bl ood suppl y causes t he rect um t o end. However ,you st i l l have an anus. I n per si st ent cl oaca, t he bl adder , vagi na, andr ectumf or m one cavi t y.

Hi r schspr ung’ s di sease i s caused by l ack of mi gr at i on of neur al crestcel l s i nt o t he col on. Above a cer t ai n poi nt , per i st al si s occur s, butbel ow t hat poi nt t her e i s an st enosi s t hat causes a backup of f l ow,causi ng t he megacol on. The di st al aganl i oni c bowel i s nar r owed.

Geni t al Devel opment Quest i ons

Where do t he pr i mordi al germ cel l s come f r om?

Pr i mor di al ger m cel l s come f r om t he epi bl ast , t hen mi gr at e t o t heext r aembryoni c yol k sac wher e t hey r emai n f or 5 weeks. They thenmi gr ate t hr ough the dorsal mesent er y t o t he post er i or body wal l next t o

T10. They ar e drawn by chemot r ophi c agent s.

The coel emi c t i ssue i s st i mul at ed by t he germ cel l s t o di f f erent i at e

i nt o t he pr i mary sex cor ds, whi ch gi ves r i se t o t he geni t al r i dge.Lat er al t o t he geni t al r i dge, t he par amesonephr i cs duct s devel op,meet i ng wi t h t he mesonephr i c duct s i nf er i orl y. I n t he mal e, t he pr i marysex cords f i rst gi ve r i se t o t he Sert ol i cel l s , as a resul t ofexpr essi on of t he SRY gene. These Ser t ol i cel l s j oi n wi t h t hepr i mor di al ger m cel l s t o devel op i nt o the t est i s cor ds. Leydi g cel l sl i ne bet ween t he t est i s cor ds and secr et e t est osterone. The Ser t ol icel l s secrete MI F, whi ch causes t he degenerat i on of t he par amesonephr i cduct i n mal es. These test i s cords wi l l not become semi ni f er ous t ubul es

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unt i l puber t y, when hi gh l evel s of t est ost er one cause t hei rdi f f erent i at i on.

I n t he f emal e, t he pr i mary sex cords degenerate, and ar e repl aced byt he secondary sex cords, whi ch ari se f r omt he coel emi c epi t hel i um. Theysur r ound t he pr i mor di al ger m cel l s, event ual l y becomi ng t he f ol l i cul arcel l s whi l e the ger m cel l s become oocyt es. The secondary sex cor ds ar eal so cal l ed the cor t i cal sex cor ds, whi ch shoul d gi ve some i dea as t owhat t hei r f uncti on i s ( t hi nk of t he cor t i cal gr anul es) .

The f unct i on of t he SRY gene i s t o i nduce t he express i on of ot her sex-det ermi ni ng genes, t he most i mport ant of whi ch i s TDF, or t est i sdet ermi ngi ng f act or. So agai n, SRY l eads t o the expr essi on of TDF,whi ch i n tur n i nduces other genes such as SOX- 9. SRY causes al l t hechanges r esponsi bl e f or becomi ng mal e – i f i t del et ed, f emal e i s t hedef aul t phenotype.

The mesonephr i c duct l eads t o t he cr eat i on of t he vas def erens i n mal es( i t acqui r es a l ayer of smooth muscl e) , whi l e i n t he f emal e themesonephr i c duct s become t he paroophor on and epoophor on.

The paramesonephr i c duct becomes t he ovar y, ut er us, cer vi x, and upperpar t of t he vagi na i n t he f emal e. The di st al part of t heparamesonephr i c duct s f use together i n t he mi dl i ne near t hepar amesonephri c t ubercl e, an out growt h of ect oderm. The paramesonephri ct uber cl e l eads t o t he si novagi nal bul bs, whi ch creat e the vagi na. Thehymen i s a bar r i er bet ween t he vagi na and UG si nus. I n t he mal e, t heparamesonephr i c duct s become t he ut r i cl e of t he pr ost ate and theappendi x of t he t est i s. I t degener at es i n mal es due t o t he ef f ect s ofMI F.

The ut erus i s f or med f r om t he f usi on of t he paramesophr i c duct s. Thevagi na i s f or med f r om t he vagi nal pl at e, whi ch i s f ormed f r om t hevagi nal bul bs. I f t he duct s don’ t f use pr oper l y, a bi hor ned ut er us, oreven a doubl e ut er us can occur . I f t he vagi nal bul bs don’ t f use, youget a doubl e vagi na, or no vagi na i f t he vagi nal bul bs don’ t devel op.

The l abi oscr ot al f ol ds f or m t he l abi a maj or a i n t he f emal e, and t hescr otum i n t he mal e. The f ol ds f use i n the mal e due to the pr esence ofDHT, whi ch i s conver t ed f r omt est oster one by 5- al pha- r educt ase. DHTal so causes the f ormat i on of t he pr ost ate and t he el ongat i on of t hephal l us, i ncl udi ng t he f usi on of t he ur et hr al f ol ds t o f or m t he peni l eur et hr a.

The peni l e uret hra i s der i ved f r om endoder m, wi t h t he except i on of t hef ossa navi cul ari s, an i ngr owt h of ect oder m. I t i s f ormed by the f usi onof ur et hr al f ol ds and canal i zat i on of t he ur et hr al pl at e.

The prost at e i s f or med f r om t he uret hra, i nduced by DHT. I t i s anendoder mal out growt h.

Ø Der i vat i ves of t he pr osencephal on, mesencephal on, and r hombencephal onWhat are the der i vat i ves of answer?- Ans. pr ocen. . . . . . . . . t el en cephal on, di en- mesen. . . . . . . . . . mesencephal on- r homben. . . . . . . . metenand, myel encephal on- t el en. . . . . . cerebra l . h, basal gangl i a

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di en. . . . . . . t hal amus and hypothal amusmesen. . . . . . . . . mi dbr ai nmet en. . . . . . . . pons, cerebel l ummyel en. . . . . . . . . . . medul l a

Ø Deri vat i ves of t he f i r st t o f our t h POUCHESWhat happens i f no t hi r d and f our t h pouch?- Ans. 1 => epi t hel i al l i ni ng of audi t or y and mi ddl e ear cavi t y- 2 => l i ni ng of pal at i ne t onsi l crypt s3 => i nf . parat hyroi d gl and, t hymus4 => sup. par at hyr oi d gl andabsence of 3rd and 4t h t hen no THYMUS AND PARATHYROI D, so Di Geor ge' sSyndrome.

Ø Der i vat i ves of t he f i r st , second, t hi r d, f our t h, and si xt h ar ches? I fanyone has a mnemoni c f or t hi s one t hat woul d be gr eat !- Ans. Each Ar ch ( mesoder m) i s associ ated wi t h a ner ve, ( f r omect oder mt hat gr ows i nt o t he ar ch) gi ves r i se t o ei t her ar t er i es, muscl es orbot h, and i s al so associ at ed wi t h a skel et al st r uct ur e ( f r om neur alcr est ) . . .

- ARCH 1 ( al l M' s)ner ve: mandi bul ar ( V- 3)ar t er y: nonemuscl e: muscl es of mast i cat i on and tensor t ympaniskel et al mal l eus ( and i ncus) maxi l l a and mandi bl e- ARCH 2: ( al l S' s)ner ve: seven ( VI I )ar t er y: nonemuscl e: st apedi us, st yl ohyoi d, and seven' s muscl es ( f aci al expr essi on)skel : l eSSer horn and upper body of hyoi d- ARCH 3: ( 3=2+1: 2 t ypes of ar t er i es, and 1 muscl e)al so: 3x3=9: ner ve i s CN I X)ner ve: XIar t er i es: r and l CC, r and l I nt er nal car ot i dmuscl e: st yl opharangeusskel : gr eat er horn and l ower body of hyoi d- ARCH 4 and 6: ( nerve i s 6+4= 10)- ARCH 4:ner ve: X and super i or l aryngealar t er y: r subcl avi an and ar ch of aor t amuscl e: cri cot hyr oi dskel : t hyroi d cart- ARCH 6:ner ve: X and r ecur r ent l aryngealar t er y: R and L Pul m ar t er i es, and Duct us Ar t .muscl e i nt r i nsi c muscl es of cr ycothyr oi dskel : al l ot her l ar yngeal cart .

Ø Der i vat i ves of t he f i r st gr oove?other grooves?What happens i f second, t hi r d and f our t h gr ooves per si st ?- Ans. 1. . . . l i ni ng of ext . audi t or y meat usi f per si si t s l eads t o phar yngeal cyst s- f i r st gr oove, and r est move! ( onl y the f i r st one per si st s anddevel ops i nt o the l i ni ng of t he EAM) i f t he ot her ones do, t hat l eadst o br anchi al cyst and l at er al cer vi cal cyst )

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Ø Ar e t he f ol l owi ng made f r om endo, meso or ect oderm?grooves?arches?pouches?- Ans. arches. . . mesoder mgr ooves. . . . ectopouches. . . . endo- way to remember . . .GAPf rom out t o i n:ect o, meso, endo

Ø What does t he l ef t horn of t he si nus venosus devel op i nto? what aboutt he r i ght hor n?- Ans. l ef t . . . coronary si nusrt . . . smoot h part of rt at r i um Ø What crani al ner ve i s associ at ed wi t h phar yngeal pouches I , I I , I I I ,I V, and VI ?I - V- 3

I I - VI II I I - I XI V - XVI - X

Ø Wher e does t he f or egut , mi dgut and hi ndgut end?- Ans. Foregut - upper duodenummi dgut - pr oxi mal 2/ 3 of t r ansver se col onhi ngut - upper par t of anal canal

Ø What i s t he adul t st r uct ur e f ound i n t he embr yo as:l ef t umb. vei n?duct us venosus?duct us ar t er i osus?umb. art ery?- Ans. l ef t umbi l i cal v. - l i g. t eresduct us ven. - l i g. venosumductus ar t er i osus - l i g. art er i osumumbi l . ar t . - medi al umbi l i cal l i gament s

Ø When does t he sept um pr i mumand sept um secundum f use? bef ore or af t erbi r t h? and what happens i f i t does not?\- Ans. f oramen oval e i s b/ w sept umpri mumand separ at es secundum. FOf uses af t er bi r t h, ot her wi se - l ef t - t o- r i ght shunt ( ASD?)

Ø What are the 5 der i vat i ves of t he vent r al mesent ery?- Ans. Lesser oment um- Hepat oduodenal , Hepat ogast r i c l i gament

- pl us fal ci f orm l i g. , coronary l i g. , t r i angul ar l i g.- Ri ght . . . al l t he l i ver l i gament s ar e f r om vent r al mesent er y( f al ci f or m, hepat oduodenal , hepat ogast r i c, cor onar y, and t r i angul ar )Al l ot her s (gast r o- , spl eno- , SI , LI , and col on) ar e der i ved f r omDorsal mesent ery

Ø What t hree t hi ngs cause t he i ndi f f erent gonad t o become a t est i s? andwhere do t hey come f r om?- Ans. Test ost r one by Leydi gMI F: by Sert ol i and f i nal l y t he mai n TDF on Y chr omosome ( shor t arm)

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Ø What are t he art er i es of t he f oregut , mi dgut and hi ndgut?What i s t he onl y or gan suppl i ed by the f or egut ar t er y, t hat i s ofmesodermal or i gi n?- Ans. cel i ac, super i or mesent er i c, i nf er i or mesent er i c.- Spl een i s a mesoder mal organ and get s bl ood suppl y f r omcel i ac ar t er y

Ø What st r uct ur e i s der i ved f r om t he pr echordal pl at e?- Ans. MOUTH.

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