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23%.%$&3 4$5##36 7#5#+ 8&5+96
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1hls e8ook ls a collaLlon of quesLlons LhaL l ask my medlcal sLudenLs aL my
8edslde Leachlng sesslons. ur Chok ?ln Llng, a brllllanL young docLor keen
on a career ln lnLernal Medlclne, was glven Lhese quesLlons on a dally
basls. 1hls was Lo help her Lo prepare for her posL graduaLe examlnaLlons.
1hese quesLlons and answers were edlLed and documenLed ln her dlglLal
dlary, Lhls e8ook ls Lhe resulL. l hope LhaL Lhls work whlch ls l8LL Lo all
wlll help sLudenLs aL boLh undergraduaLe and posL graduaLe levels.
! #$#%&'($ ()%* $+,,- (, '.. ()$ ($'&)$/* ,0 ()%* '1&%$1( '/(2
"# $%&' ()& %&&
*++,-*./01 *234 -5601 7*1 8234-9/.:0
;; *.#<= ;>?@

loreword by ur ng klan Seng, Lhe founder of AequanlmlLas

1he Dear |n L|ng Ser|es... 1he words are of course noL Lo be Laken
llLerally... "uear" ls Lhe hearL aLLlLude LhaL rof unna Wong brlngs Lo hls
Leachlng, he loves hls sLudenLs...

?ln Llng ls a real name buL of course lL ls also a meLaphor for Lhe PC,
MC, ConsulLanL, Medlcal sLudenL who ls passlonaLe for medlclne and
paLlenL... please do noL allow overworked, underpald ?ln Llng Lo be Lhe
sole person lnLeracLlng wlLh rof Wong... Lhlnk of LhaL... l am also a ?ln
Llng (older, male and faLLer verslon) and rof Wong ls also addresslng me
when he says, uear ?ln Llng...and ?ln Llng should be proud LhaL rof
Wong has used her name...as a meLaphor

l love Lhe LlLle and so do many of Lhe people ln kluang and perhaps
around Lhe world!



uear ?ln Llng,
Csler sald LhaL Lo succeed you musL Pave a Calllng, 1he Calllng Lo be Lhe
8LS1 hyslclan LhaL you can be, Lhe mosL compasslonaLe docLor avallable,
and Lhe mosL dedlcaLed sLudenL soaklng up all LhaL your senlors can
Leach.

Lven afLer he was well esLabllshed ln medlclne, Csler was urged Lo
conslder oLher career paLhs eg unlverslLy presldency and pollLlcs, buL he
always decllned. 1hank goodness for LhaL. ollLlcs would have kllled hlm
off early.

ln perhaps hls greaLesL speech Lo a medlcal sLudenL body, LlLled
AequanlmaLus," he spoke of havlng found hls calllng. ?ou musL have Lhe
same calllng LhaL wlll push you Lo sLudy Llll Lhe wee hours, Lo see paLlenLs
Llll you drop from exhausLlon, Lo learn llke your llfe depends on lL, and
hopefully Lo also Leach your [unlors llke a woman possessed.

"1o prevent d|sease, to re||eve suffer|ng, and to hea| the s|ckth|s |s our
work. 1he profess|on |n truth |s a sort of gu||d or brotherhood, any
member of wh|ch can take up h|s ca|||ng |n any part of the wor|d and
f|nd brethren whose |anguage and methods and whose a|ms and ways
are |dent|ca| w|th h|s own."

uest|ons
1) CN n.LCkI
Dear |n L|ng,

What can we use |n n res|stant to Amox]c|arythro]I comb|nat|on treatment?

1he lssue ls whaL Lo do wlLh LreaLmenL fallures. 1he success raLe for Lhe current
comb|nat|on |s assumed to be over 8S. lL ls llkely LhaL Lhe success raLes are
gradually decreaslng as macro||de res|stance becomes more prevalenL. 1here ls
some cross-reslsLance Lo clarlLhromycln from Lhe use of oLher macrolldes.

AfLer fallure of a comblnaLlon of l, amoxlclllln and clarlLhromycln, a LheoreLlcally
correcL alLernaLlve would be Lhe use, as second opLlon, of oLher l-based Lrlple
Lherapy lncludlng amoxlclllln (LhaL does noL lnduce reslsLance) and meLronldazole
(an anLlbloLlc noL used ln Lhe flrsL Lrlal). Powever ln pracLlce Lhls approach as
second-llne LreaLmenL has proven Lo be dlsappolnLlng (approx 30 eradlcaLlon
raLe).

Levof|oxac|n-based 'rescue' therapy appears to be the best second-||ne strategy,
represenLlng a good alLernaLlve Lo quadruple Lherapy ln paLlenLs wlLh prevlous l-
clarlLhromycln-amoxlclllln fallure - Lhls LreaLmenL has hlgher efflcacy, slmpllclLy of
use (beLLer compllance) and less adverse effecLs. Levofloxacln has, ln vlLro,
remarkable acLlvlLy agalnsL P. pylorl and prlmary reslsLance ls relaLlvely lnfrequenL
(when compared wlLh meLronldazole or clarlLhromycln).

A comblnaLlon of a I, amox|c||||n and |evof|oxac|n, as f|rst-||ne reg|men, has
mean erad|cat|on rates of about 90. lor paLlenLs wlLh one prevlous eradlcaLlon
fallure, P. pylorl cures raLes range from 60 Lo 94. A recenL sysLemaLlc revlew
showed a mean eradlcaLlon raLe wlLh levofloxacln-based 'rescue' reglmens
(comblned wlLh amoxlclllln and a l ln mosL sLudles) of 80, whlch represenLs a
relaLlvely hlgh flgure when conslderlng 'rescue' Lherapy wlll have have eradlcaLlon
raLes lower Lhan flrsL-llne LreaLmenLs. A systemat|c rev|ew found h|gher n. py|or|
cure rates w|th 10-day than w|th 7-day reg|mens w|th the |evof|oxac|n-amox|c||||n-
I comb|nat|on |n part|cu|ar (80 versus 68), suggest|ng that the |onger (10-
day) therapeut|c scheme shou|d be chosen. 1he da||y dose |s st||| unc|ear but
S00mg da||y may be as effect|ve as S00mg bd.

|ease check w|th Urea 8reath 1est post treatment for cure!



2) CN LIIDS
Dear y|n ||ng,
n|gh cho|estero| p|us h|gh 1r|g|ycer|des |s common c||n|ca| prob|em. Stat|ns a|one
often do not return one to norma| phys|o|ogy.

WnA1 can you offer?

http:]]www.ncb|.n|m.n|h.gov]m]pubmed]23324122]
Adverse events following statin-fenofibrate therapy versus statin alone: a meta-
analysis of randomized controlled trials.
Geng Q, et al. Journal Clin Exp Pharmacol Physiol. 2013 Mar;40(3):219-26. doi: 10.1111/1440-1681.12053.

AbsLracL
1he comblnaLlon of fenoflbraLe wlLh sLaLlns ls a beneflclal LherapeuLlc opLlon for
paLlenLs wlLh mlxed dysllpldaemla, buL concerns abouL adverse evenLs (ALs) make
physlclans relucLanL Lo use Lhls comblnaLlon Lherapy. Medllne, Lmbase and Lhe
Cochrane Llbrary were searched Lo ldenLlfy 13 randomlzed conLrolled Lrlals,
lnvolvlng 7712 paLlenLs, of sLaLln-fenoflbraLe Lherapy versus sLaLln alone for revlew.
1here were slgnlflcanL decreases ln low-denslLy llpoproLeln-cholesLerol, Lrlglycerldes
and LoLal cholesLerol and lncreases ln hlgh-denslLy llpoproLeln-cholesLerol ln
paLlenLs recelvlng comblnaLlon Lherapy compared wlLh sLaLln Lherapy alone. 1he
lncldence of amlnoLransferase elevaLlons ln Lhe fenoflbraLe-sLaLln Lherapy group
was slgnlflcanLly hlgher Lhan ln Lhe sLaLln monoLherapy group (odds raLlo (C8), 1.66,
93 confldence lnLerval (Cl) 1.17-2.37, < 0.03). 1he lncldence of elevaLed creaLlne
klnase levels (C8 0.88, 93 Cl 0.63-1.23, > 0.03), muscle-assoclaLed ALs (C8 0.98,
93 Cl 0.88-1.09, > 0.03) and wlLhdrawals aLLrlbuLed Lo llver and muscle
dysfuncLlon dld noL dlffer slgnlflcanLly beLween Lhe Lwo groups. 1he efflcacy of
fenoflbraLe + sLandard-dose sLaLln and lncldence of ALs ln Lhe fenoflbraLe +
sLandard-dose sLaLln group were almosL ldenLlcal Lo Lhose ln Lhe fenoflbraLe-sLaLln
group. ln concluslon, comblnaLlon Lherapy lmproves Lhe blood llpld proflle of
paLlenLs. lenoflbraLe-sLaLln comblnaLlon Lherapy appears Lo be as well LoleraLed as
sLaLln monoLherapy. hyslclans should conslder fenoflbraLe-sLaLln comblnaLlon
Lherapy ln paLlenLs buL monlLor amlnoLransferase levels Lo avold hepaLlc
compllcaLlons.

L: l learnL LhaL lL's also lmporLanL Lo reallze LhaL boLh a|coho| and |nsu||n res|stance
can g|ve a h|gh 1G. lnsulln reslsLance caused Lhe breakdown of Lrlglycerldes and
release llA. one dleLary advlce ls Lo cuL down slmple carbs and sugars Lo conLrol 1C.

1G w||| a|so |ncrease SMALL, DLNSL LDL part|c|e, aka LDL3, wh|ch |s h|gh|y
atherogen|c compared to LDL1 wh|ch |s |arger and |ess dense. we cannoL measure
boLh of Lhem, hence Lhe surrogate marker of h|gh 1G and |ow nDL ref|ects the
sma|| and dense LDL3 part|c|e. by conLrolllng 1C wlLh a flbraLe, we make Lhe small
dense LuL become blgger less dense LuL, and decrease Lhe overall aLherogenlc rlsk,
desplLe no change ln LuL levels.

We rarely use gemflbrozll now.

Cnly flbraLe and nlacln lncrease one's PuL. buL nlacln makes one look llke a crab-
flushlng!!

We may comblne wlLh uslng a sLaLln aL nlghL and fenoflbraLe ln Lhe mornlng.

kCI : Under what cond|t|ons w||| we st||| use gemf|bros||?

Many of our paLlenLs on follow up have renal lmpalrmenL of varlous sLages. 1hey are
commonly monlLored by eCl8 whlch ls convenlenL vs 24h urlne for CCl.

Ienof|brate |ncreases creat|n|ne |eve|s s|gn|f|cant|y hence a ca|cu|ated eGIk w||| be
fa|se|y |owered. Gemf|bros|| avo|ds th|s effect.

hLLp://www.ncbl.nlm.nlh.gov/m/pubmed/12372933/
Fenofibrate increases creatininemia by increasing metabolic production of
creatinine.

Hottelart C, et al. Journal Nephron. 2002;92(3):536-41.
AbsLracL
lenoflbraLe ls a poLenL hypollpemlc agenL, wldely used ln paLlenLs wlLh renal
lnsufflclency ln whom dysllpldemla ls frequenL. A moderaLe reverslble lncrease ln
creaLlnlne plasma levels ls an esLabllshed slde effecL of fenoflbraLe Lherapy, whlch
mechanlsm remalns unknown. We have prevlously reporLed LhaL ln 13 paLlenLs wlLh
normal renal funcLlon or moderaLe renal lnsufflclency, Lwo weeks of fenoflbraLe
Lherapy lncreased creaLlnlnemla wlLhouL any changes ln renal plasma flow and
glomerular fllLraLlon raLe [1]. ln 13 addlLlonal paLlenLs, muscular enzymes (AS1, C1,
Ck, LuP) and myoglobln were measured before and afLer 2 weeks on fenoflbraLe,
and Lhe values of creaLlnlnemla obLalned by Lhe !affe Lechnlque and PLC were
compared. Ck and AS1 acLlvlLy and plasma myoglobln lncreased ln 2 paLlenLs wlLh
fenoflbraLe, buL muscular enzymes remalned unchanged ln Lhe populaLlon as a
whole, and were noL correlaLed Lo Lhe changes ln creaLlnlnemla. 1he changes ln
creaLlnlnemla lnduced by fenoflbraLe measured by Lhe !affe Lechnlque were sLrongly
correlaLed Lo Lhose measured by PLC (r(2) = 0.673, p = 0.0006). Analysls of Lhe
pooled daLa of Lhe Lwo arms of Lhe sLudy showed ln 26 paLlenLs LhaL Lwo weeks of
fenoflbraLe Lherapy efflclenLly reduced LoLal cholesLerol and Lrlglycerldes plasma
levels, and ralsed creaLlnlnemla from 139 +/- 8 Lo 160 +/- 10 mlcromol/l (p <
0.0001), buL conflrmed LhaL creaLlnlnurla also lncreased Lo Lhe exLenL LhaL creaLlnlne
clearance remalned unchanged (68 +/- 6 vs. 67 +/- 6 ml/mln, n.s.). lL ls concluded
LhaL Lhe lncrease ln creaLlnlnemla lnduced by fenoflbraLe ln renal paLlenLs does noL
reflecL an lmpalrmenL of renal funcLlon, nor an alLeraLlon of Lubular creaLlnlne
secreLlon, and ls noL falsely lncreased by a dosage lnLerference. lenoflbraLe-lnduced
lncrease of dally creaLlnlne producLlon ls nelLher readlly explalned by acceleraLed
muscular cell lysls. lL ls proposed LhaL fenoflbraLe lncreases Lhe meLabollc
producLlon raLe of creaLlnlne.


3) CN CAN1LIL'S LINL
uear ?ln Llng,

Who |s S|r Iames Cant||e and why |s h|s contr|but|on not on|y to med|c|ne but a|so
to As|a and the wor|d?

CanLlle's llne ls named ln hls honour. WhaL ls Lhls llne and how ls lL so lmporLanL Lo
our undersLandlng of Lhe LreaLmenL of llver Lumours? Lveryday ln my work l look
ouL for dlseases and carefully see lf lL ls Lo Lhe lefL or rlghL of CanLlle's llne and hence
poLenLlally LreaLable.

ur !ames CanLlle was a loundaLlon rofessor aL Lhe prlmordlal College of Medlclne
ln Pongkong (laLer Lo become Lhe laculLy of Medlclne aL Lhe unlverslLy of
Pongkong). ln hls very flrsL baLch was a young brllllanL Chlnese lad named Sun ?aL
Sen. 1eachers of old llke some Leachers Loday loved Lhelr sLudenLs llke Lhelr own
chlldren (followlng Lhe PlppocraLlc oaLh Lhe relaLlonshlp ls akln Lo a laLher-
Son/uaughLer bond).

lL was also ln Pongkong LhaL he dld hls semlnal work on Lhe llver. ?ears laLer when
ur Sun ?aL Sen Lhe revoluLlonary was kldnapped by Lhe Manchurlan reglme ln
London and almosL deflnlLely headed back home for hls head Lo be separaLed from
hls neck, lL was Slr !ames CanLlle LhaL ur Sun Lurned Lo for help and he organlsed a
press campalgn and much publlclLy LhaL ulLlmaLely pressured Lhe Manchurlan
auLhorlLles Lo release ur Sun, once agaln provlng Lhe power of Lhe pen vs Lhe sword.

ur Sun subsequenLly wenL on Lo be Lhe laLher of Modern Chlna.

hLLp://www.ncbl.nlm.nlh.gov/pmc/arLlcles/MC2826664/
Thomas M van Gulik and Jacomina W van den Esschert
AbsLracL
As early as 1897, Slr !ames CanLlle publlshed a serles of observaLlons of
exLraordlnary slgnlflcance ln Lhe face of how we now look upon porLal blood supply
and Lhe pre-resecLlonal use of porLal veln llgaLlon or embollzaLlon Lo lnduce
hyperLrophy of Lhe parL of Lhe llver we lnLend Lo preserve. ln Lhe roceedlngs of Lhe
AnaLomlcal SocleLy of CreaL 8rlLaln and lreland, he descrlbes performlng an auLopsy
on a paLlenL ln whlch Lhe rlghL slde of Lhe llver was reduced Lo a mass of flbroLlc
Llssue whereas Lhe lefL slde of Lhe llver showed a marked hyperLrophy.
1*
Pe noLed
'A=.A A=B =(CB#A#%C=( %D A=B /BDA :)"B E%)&B" $)A= A=B .A#%C=)B" #)'=A :)"B1 .A . /)&B
"#.$& A=#%F'= A=B DF&"F: %D A=B './/G/.""B# A% A=B <B&AB# %D A=B )&DB#)%# HB&. <.H.
.A A=B G.<I %D A=B /)HB#'. Pe assumed LhaL an abscess had desLrucLed Lhe rlghL lobe of
Lhe llver, and LhaL Lhls resulLed ln a compensaLory hyperLrophy of Lhe conLralaLeral
parL of Lhe llver. Pence, he concluded LhaL Lhe llne connecLlng Lhe fundus of Lhe
gallbladder wlLh Lhe cenLre of Lhe lnferlor vena cava lndlcaLed Lhe mld-llne of Lhe
llver, unllke common oplnlon aL LhaL Llme whlch consldered Lhe umblllcal flssure as
Lhe dlvlslon of Lhe rlghL and lefL llver lobes.
Pe corroboraLed hls observaLlons by performlng experlmenLs ln whlch he ln[ecLed
Lhe rlghL and lefL dlvlslons of Lhe porLal veln wlLh coloured dyes showlng LhaL Lhe
ln[ecLed areas meL along a llne connecLlng 'A=B DF&"F: %D A=B './/G/.""B#' wlLh 'A=B
:C%A $=B#B A=B )&DB#)%# HB&. <.H. '#%%HB: A=B G.<I %D A=B /)HB#'. 1hls llne we sLlll
refer Lo as CanLlle's llne (llg. 1) lndlcaLlng Lhe anaLomlcal mld-llne of Lhe llver and
deflnlng Lhe border beLween Lhe rlghL and lefL llver segmenLs ln Lhe plane of Lhe
mlddle hepaLlc veln. As he reallzed LhaL Lhe rlghL and lefL llver were perfused by Lwo
separaLe sLreams of Lhe porLal veln, he recognlzed Lhe poLenLlal Lhls phenomenon
could have for hepaLlc surgery.
llgure 1
CanLlle's llne represenLs Lhe anaLomlcal mld-llne of Lhe llver connecLlng Lhe fundus
of Lhe gallbladder wlLh Lhe cenLre of Lhe lnferlor vena cava.
Pe percelved Lhe consequences Lhe waLershed beLween Lhe rlghL and lefL llver lobes
could have for Lrauma of Lhe llver by wrlLlng 'J=B /)HB#1 $=B& :C/)A %# D)::F#B" G( .
G/%$1 .: GBA$BB& A=B GFDDB#: %D #.)/$.(K<.##).'B:1 :C/)A: ./%&' A=B L)"K/)&B %D A=B
/)HB# )& C#BDB#B&<B A% .&( %A=B#'. Pe also foresaw LhaL Lhls would noL necessarlly
resulL ln ma[or bleedlng as '=.BL%##=.'B =.: /B:: A% GB "#B."B" .: A=B /)HB# ):
)&<):B" %# A%#& )& A=B &B)'=G%#=%%" %D A=.A /)&B (l.e Lhe mld-llne)'. lndeed ln blunL
abdomlnal Lrauma, Lhe llver may be compleLely fracLured along CanLlle's llne
wlLhouL any ma[or bleedlng from LhaL plane. We were able Lo conflrm Lhls message
recenLly ln a paLlenL admlLLed afLer blunL abdomlnal Lrauma who had fracLured hls
llver along CanLlle's llne (llg. 2) and who had been successfully managed by
conservaLlve LreaLmenL wlLhouL Lhe need for any blood Lransfuslon.
llgure 2
ConLrasL enhanced abdomlnal compuLed Lomography (C1) scan of a paLlenL
admlLLed afLer blunL abdomlnal Lrauma showlng a fracLure of Lhe llver along
CanLlle's llne, runnlng beLween Lhe medlal borders of segmenL lv and segmenLs v/
vlll.
Comlng back Lo hls lnlLlal observaLlon aL Lhe auLopsy, he noLed Lhe './L%:A
B/BC=.&A)&B' hyperLrophy of Lhe lefL slde of Lhe llver aL Lhe expense of a greaLly
aLrophled rlghL slde '$=)<= /%%IB" /)IB1 .&" C#.<A)<.//( $.:1 . LB#B .CCB&".'B A% A=B
/BDA :)"B %D A=B %#'.&'. Cn dlssecLlon of Lhe llver he found Lhe velns, arLery and ducL
of Lhe rlghL slde of Lhe llver Lo be obllLeraLed whereas Lhose Lo Lhe lefL slde were
proporLlonally lncreased ln dlameLer. lrom Lhls observaLlon he concelved LhaL by
ellmlnaLlng blood supply Lo one slde of Lhe llver, a funcLlonal advanLage for Lhe
spared half of Lhe llver could be creaLed resulLlng ln hyperLrophy of LhaL parL of Lhe
llver. Pe Lhen wroLe 'MA ): A=B%#BA)<.//( C%::)G/B A% A)B A=B HB::B/: %D %&B :)"B .A A=B
'.AB %D A=B /)HB#1 :FCC/()&' .& .G&%#L./ '#%$A= )& %&B %# %A=B# %D A=B /)HB# /%GB:1
/B.H)&' A=B %A=B# :)"B A% "% A=B $%#I'. 8eallzlng Lhe lmporLance Lhls phenomenon
could have for resecLlng Lhe llver, he conLlnued 'M <%LLB&" A=): :FGEB<A A% .// A=%:B
$=% .#B $%#I)&' .A A=B :F#'B#( %D A=B /)HB#N .&" M GB/)BHB A=.A )D1 )& A=B =.&": %D
DFAF#B %G:B#HB#:1 A=B :A.ABLB&A: M =.HB L."B #B<B)HB </%:B# )&HB:A)'.A)%&1 A=B
:F#'B#( %D A=B /)HB# $)// GB ."H.&<B" . :ABC'. 1he foreslghL he had was amazlng, wlLh
Lhe flrsL formal rlghL hemlhepaLecLomy belng performed 33 years laLer ln 8eau[on
PosplLal ln arls and Lhe flrsL cllnlcal porLal veln embollzaLlon belng performed ln
!apan 83 years afLer hls reporL.
Slr !ames CanLlle (llg. 3) was born ln 1831 ln 8anffshlre, ScoLland.

AfLer flnlshlng hls
medlcal sLudles aL Aberdeen unlverslLy, he Lralned as a surgeon aL Charlng Cross
PosplLal ln London. Pe became a fellow of Lhe 8oyal College of Surgeons ln 1877 and
wenL on Lo work as a surgeon aL Charlng Cross. lnLeresLlngly, ln 1887 he moved Lo
Pong kong where he became a co-founder of a new medlcal school, Lhe Pong kong
College of Medlclne for Chlnese, Lhe forerunner of Lhe laculLy of Medlclne of Lhe
unlverslLy of Pong kong. ln Lhls lnsLlLuLlon, of whlch he led Lhe surglcal deparLmenL,
CanLlle carrled ouL Lhe auLopsy descrlbed above. Cne of hls sLudenLs was Sun?aL Sen
who would laLer become Lhe flrsL provlslonal presldenL of Lhe 8epubllc of Chlna.
When Lhls Chlnese leader was deLalned aL Lhe Chlnese LegaLlon ln London ln 1896,
CanLlle played a key role ln hls release. ln 1897 CanLlle reLurned Lo pracLlce ln
London.
llgure 3 Slr !ames CanLlle (1831-1926)
1he dlvlslon of Lhe porLal veln lnLo a rlghL and lefL branch aL Lhe llver hllum was
already reporLed by Lhe anaLomlsLs of Lhe 17
Lh
cenLury. lrancls Cllsson (1398-1677)
ln hls LexLbook AnaLomla PepaLls descrlbed cannulaLlng Lhe porLal veln and maklng
casLs of Lhe porLal venous sysLem.

CanLlle, however, showed LhaL by Lhe separaLe
porLal vasculaLure, Lhe llver could be funcLlonally dlvlded lnLo an anaLomlcally
dlsLlncL rlghL and lefL half. 1he poLenLlal of one half of Lhe llver Lo hyperLrophy when
Lhe oLher half ls deprlved of lLs blood supply was furLher conflrmed ln experlmenLal
sLudles by 8ous and Larlmore ln 1920 and Schalm and colleagues ln 1936. 1he laLLer
auLhors from Arnhem, Lhe neLherlands, made reference Lo CanLlle's work and ldeas
on unllaLeral occluslon of Lhe porLal veln. Surprlslngly, porLal veln occluslon found lLs
way Lo cllnlcal appllcaLlon only ln 1982, when Makuuchl and laLer, klnoshlLa,
publlshed Lhelr flrsL experlences wlLh porLal veln embollzaLlon ln paLlenLs. Pence,
alLhough Lhe credlL for Lhe flrsL cllnlcal porLal veln occluslons goes Lo Lhese
colleagues ln !apan, lL should be remembered LhaL ln 1897, !ames CanLlle from
ScoLland had already lald down Lhe concepL of pre-operaLlve porLal veln occluslon.
?L: Cant||e's L|ne de||neates the SUkGICAL anatomy of the ||ver, a llne connecLlng
Lhe fundus of Lhe C8 and Lhe lvC, separaLlng Lhe llver lnLo Lhe surglcal LefL and
surglcal 8lghL lobe. whlle, Lhe lalclform LlgamenL we see from Lhe anLerlor aspecL of
Lhe llver ls [usL Lhe anaLomlcal llne, noLhlng Lo do wlLh lLs funcLlon nor help wlLh
surgery.

?ou ofLen look for Lhe hepaLlc velns on uSC whlle placlng your probe subcosLally. lL's
Lhe one wlLh Lhln walls as opposed Lo Lhe Lhlcker walls of Lhe porLal velns. 1he
mlddle and rlghL hepaLlc veln [oln Lhe lvC, showlng us Lhe 'layboy Slgn'. A Lhln
playboy lf lLs normal. When you see leslons susplclous of PCC/meLs, lf Lhey are on
one slde of Lhe CanLlle's llne, Lhere ls hope of Lumour resecLlon for Lhe paLlenL. lf lL
crosses boLh lobes, unforLunaLely we wlll have Lo prepare Lhe paLlenL for Lhe worsL.



4) CN 1nALASSLMIA
Dear y|n ||ng,

esterday a student to|d me that her mother has heavy menses and |s chron|ca||y
anaem|c. Low ferr|t|n conf|rmed. 1he student herse|f |ooked a b|t pa|e too.
I asked |f she has any fam||y h|story of 1ha|assem|a. And she rep||ed that Screen|ng
for 1ha|asaem|a for her mother was done at the same t|me. And |t |s 'norma|'.

What are your concerns as a consu|tant on know|ng th|s and what w||| you adv|se?
?L: 1halassemla cannoL be screened when Lhere ls concurrenL lron deflclency
anemla.. PbA2 wlll be lALSLL? nC8MAL. We have Lo correcL Lhe lron deflclency
flrsL. 8epeaL ferrlLln- normal range only Lhen we can do a Lhalassemla screenlng.
rof : lron deflclency ls common ln adulL women. lL ls a serlous poLenLlal
compllcaLlng facLor when LesLlng for a Lhalassaemla carrler sLaLe. 8oLh lron
deflclency and a Lhalassaemla carrler sLaLe may resulL ln a low MCv and MCP. 8uL
Lhe MCv ln Lhalasaemla ls generally very low. LryLhrocyLosls ls more llkely Lo be
caused by Lhalassaemla, buL lL ls noL a dlagnosLlc flndlng.
1he dlagnosLlc crlLerlon for beLa Lhalassemla LralL (811) ls elevaLed Pb-A2 levels.
Iron def|c|ency anem|a (IDA) reduces the synthes|s of nb-A2, resu|t|ng |n reduced
nb-A2 |eve|s, so pat|ents w|th co-patho|og|ca| cond|t|ons 811 w|th IDA, may have a
norma| |eve| of nb-A2.
Many soclo-economlc facLors llke worm lnfesLaLlon, poor dleL, mulLlple pregnancles,
docLor unawareness resulL ln lnLerpreLaLlon of Lhese sub[ecLs as slmply lron
deflclency anaemla or worse as normal.

kCI : What |s the danger of [ust g|v|ng |ron to pat|ents und|agnosed or
m|sd|agnosed as |ron def|c|ency? 1e|| me about nepc|d|n and |ts ro|e |n |ron
phys|o|ogy. What happens |n 1ha|asaem|a carr|ers?
?L : Pepcldln regulaLes Lhe lron absorpLlon ln our body. nepc|d|n |nh|b|ts |ron
absorpt|on. Low hepcldln encourage lron absorpLlon and vlce versa. When Lhere ls
lncrease eryLhropolesls.. hepcldln wlll be low so LhaL absorpLlon of lron ls lncreased,
and vlce versa. uurlng lnflammaLlon, hepcldln also an acuLe phase reacLanL ls hlgh,
lron absorpLlon ls less so conLrlbuLlng furLher Lo anemla of chronlc dlseases.


8eLa Lhal carrlers do noL have severe anemla buL Lhey have lncrease ln
eryLhropolesls and low hepcldln levels. 1hey can have lron overload from all Lhe
lncreased lron absorpLlon.
When we have noL dlagnosed lron deflclency anemla, glvlng lron Lo pL who has
oLher dlseases such as beLa Lhal LralL may cause lron overload! More so wlLh Lhelr
Lendency Lo have an lncreased lron absorpLlon. We are dolng more harm Lhan good
Lo Lhem
8Cl : lL ls uncommon Lo Lransfuse paLlenLs wlLh 811 unless Lhelr Pb ls
unaccepLably low. MosL of Lhem adapL very well Lo Lhe chronlc anaemla.
lurLhermore blood Lransfuslon also Lransfuses lron besldes Lhe rlsk of blood borne
dlseases. Pavlng sald LhaL l am aware of some 811 female paLlenLs who requlre
blood Lransfuslon. 1hey llkely have beLa Lhalasaemla lnLermedla
1he Lerm "Lhalassemla" ls derlved from Lhe Creek rooL words for "anemla" and
"sea" because Lhe Lhalassemla syndromes were lnlLlally belleved Lo be resLrlcLed Lo
populaLlons around Lhe MedlLerranean Sea
ln mosL adulLs, 97 of the hemog|ob|n produced |s hemog|ob|n A (nbA), wh|ch has
two a|pha-g|ob|n cha|ns and two beta-g|ob|n cha|ns. 1he rema|n|ng 2 to 3 of
adu|t hemog|ob|n |s hemog|ob|n A2, wh|ch |s composed of a pa|r of a|pha-g|ob|n
cha|ns and a pa|r of de|ta-g|ob|n cha|ns. In some adu|ts, feta| hemog|ob|n nbI,
wh|ch |s composed of two a|pha- and two gamma-g|ob|ns, may cont|nue to be
produced, but |t does not typ|ca||y exceed 2 of the hemog|ob|n product|on

1halassemla lnLermedla ls a Lerm Lo descrlbe paLlenLs wlLh beLa-Lhalassemla ln
whom Lhe cllnlcal severlLy falls beLween Lhe mlnor and ma[or forms. 1he mlnor
forms, Lend Lo be cllnlcally mlld, lf noL asympLomaLlc

1here are Lwo beLa-globln genes conLrolllng Lhe producLlon of beLa-globln, one on
each copy of chromosome 11. 1he beLa-globln gene may have a muLaLlon LhaL
resulLs ln Lhe producLlon of no beLa-globln, noLed as [beLa]0, or lL may have a
muLaLlon LhaL resulLs ln reduced producLlon of beLa-globln, noLed as [beLa]+. 8eLa-
Lhalassemla LralL occurs when a person acqulres a normal beLa-globln gene and a
Lhalassemlc beLa-globln gene, or Lwo Lhalassemlc beLa-globln genes LhaL sLlll
produce mlnlmal Lo moderaLe amounLs of beLa-globln chalns

Survlval advanLage
1he 88C ln a paLlenL wlLh beLa-Lhalassemla LralL ls more rlgld and dehydraLed Lhan a
normal 88C.

uue Lo slmllarlLles ln Lhe dlsLrlbuLlons of malarla and Lhe Lhalassemlas, |t was
hypothes|zed that the deve|opment of tha|assem|a tra|ts offered some protect|on
|n ma|ar|a| |nfect|on. Alpha-Lhalassemla may offer some general proLecLlon agalnsL
severe malarla. 8eLa-Lhalassemlc paLlenLs may be proLecLed from malarla by an
enhanced phagocyLosls of Lhe early lnLraeryLhrocyLlc form of malarla, called rlngs, ln
beLa-Lhalassemlc cells.

1halassemla LralL may be manlfesLed by pallor, faLlgue, or oLher nonspeclflc
complalnLs assoclaLed wlLh anemla. 1here may be a famlly hlsLory of anemla, ofLen
lL has been mlsLakenly dlagnosed as lron deflclency. 1he famlly's eLhnlc orlgln may
be suggesLlve of a Lhalassemla LralL lf Lhey are from Lhe MedlLerranean reglon, or
SouLheasL Asla. 1here ls frequenLly a marked mlcrocyLosls, wlLh a LCW mean
corpuscular volume, and mlld Lo moderaLe hypochromla of Lhe 88Cs. 1he
character|st|c k8C count |ndex f|nd|ngs for beta-tha|assem|a tra|t are a h|gh k8C
count, m||d anem|a, and m|crocyt|c, hypochrom|c ce||s. 1he mean corpuscu|ar
hemog|ob|n concentrat|on (MCnC) tends to rema|n |n the norma| range of va|ues.
M||d sp|enomega|y may be found |n peop|e w|th beta-tha|assem|a tra|t

ulagnoslng Lhe Lhalassemla LralLs can be dlfflculL because Lhe lab values may mlmlc
lron deflclency, Lhere may even be concurrenL lron deflclency. If a pat|ent has a |ow
MCV, a serum ferr|t|n |eve| shou|d be obta|ned.

If the ferr|t|n |s |ow, the |ron def|c|ency shou|d be corrected, and the MCV
re|nterpreted afterward. lf Lhe ferrlLln ls normal, a hemoglobln elecLrophoresls wlll
ldenLlfy hemogloblns A, l, and a number of oLher hemoglobln varlanLs, along wlLh
Lhe esLlmaLlon of Lhe PbA2 level. eop|e w|th an e|evated |eve| of nbA2 a|ong w|th
hypochrom|c, m|crocyt|c k8Cs have a beta-tha|assem|a tra|t . If the nbA2 |s
border||ne h|gh to norma|, |t |s ||ke|y that they have a|pha-tha|assem|a or a
comb|nat|on of a|pha-beta tha|assem|a. A|pha-tha|assem|a tra|t |s often regarded
as a d|agnos|s of exc|us|on because the hemog|ob|n e|ectrophores|s does not
def|n|t|ve|y prove |t |s an a|pha-tha|assem|a tra|t. 1he def|n|t|ve test|ng for a|pha-
tha|assem|a tra|ts wou|d be genet|c test|ng that can determ|ne the exact number
of de|et|ons of the a|pha-g|ob|n genes. 1hese tests, however, are expens|ve and
not read||y ava||ab|e.

|ease a|ways remember that Iron def|c|ency may obscure the resu|ts of the
hemog|ob|n e|ectrophores|s |f tha|assem|a tra|t |s present as |t fa|se|y norma||ze
the |eve| of nbA2
uear ?ln Llng

are you aware of experlmenLal LreaLmenLs ln 1halassaemla offerlng a posslble cure.
1he experlmenLal LreaLmenLs lnclude lnduclng Lhe body Lo produce feLal
hemoglobln agaln as opposed Lo adulL hemoglobln, and Lhe lnLroducLlon of gene
Lherapy. 1he LreaLmenLs currenLly belng Lrled are bone marrow or umblllcal sLem
cell LransplanLs.

leLal hemoglobln changes Lo adulL hemoglobln laLer ln chlldhood. lL was noLed LhaL
lnfanLs born wlLh slckle cell anemla showed no slgns of slckllng unLll Lhe feLal
hemoglobln was replaced. lL was exLrapolaLed LhaL lf a chlld wlLh Lhalassemla could
have Lhelr adulL hemoglobln replaced by feLal hemoglobln once agaln, Lhls would be
beneflclal. A search began Lo flnd a drug LhaL could reverse Lhe neonaLal swlLch ln
hemogloblns. 1hls would need Lo be a drug LhaL changed gene regulaLlon called a
hypomeLhylaLor.

A drug was found (3-azacyldlne) LhaL worked well buL caused severe slde effecLs. We
awalL new drugs.

lL ls hoped LhaL evenLually Lhalassemla wlll be LreaLed by replaclng Lhe defecLlve
globln gene wlLh a normally worklng gene

resenLly Lhe LreaLmenL of cholce ls sLem cell LransplanL. PealLhy sLem cells sources
lnclude bone marrow and umblllcal cord blood from healLhy donors. umblllcal cord
blood ls a more readlly avallable source of sLem cells. 1he recenL movemenL of
umblllcal sLem cell collecLlon aL blrLhs ls bulldlng up banks of posslble Llssue
maLches. 1he goal of sLem cell LransplanLaLlon ls slmllar Lo gene Lherapy, le replace
Lhe defecLlve blood cells found ln Lhalassemla wlLh healLhy normal blood cells.

As far as exams ls concerned, no dlscusslon wlll be compleLe wlLhouL menLlon of
LreaLmenL 8LlC8L concepLlon. 1hls ls parLlcularly lmporLanL ln hlgh prevalence
reglons.

8oLh parenLal geneLlc screenlng and prelmplanLaLlon dlagnosls from a slngle
blasLomere ln ln-vlLro ferLlllzaLlon have LoLally changed Lhe way of llfe ln some
counLrles wlLh prevlously hlgh numbers of chlldren wlLh Lhalassemla. 1hroughouL
Lhe MedlLerranean, educaLlon campalgns have Laken place for enLlre counLrles,
especlally LargeLlng secondary school Leens. LducaLlon and free Lhalassemla cllnlcs
provlde cholces abouL blrLh conLrol, maLe selecLlon, adopLlon, feLal LesLlng, arLlflclal
lnsemlnaLlon by donor, and aborLlon. Lven Lhe conservaLlve Creek CrLhodox Church
agreed Lo requlre LhaL all couples applylng for a marrlage cerLlflcaLe be preLesLed for
Lhalassemla carrler LralL. AborLlon, whlch was prevlously lllegal, has become legal ln
pregnancles dlagnosed wlLh Lhalassemla.

needless Lo say such sLeps have Lhelr proponenLs and opponenLs.

3) |n L|ng,
A 2S-year-o|d Ch|nese woman was referred for rev|ew of her anaem|a. She |s
pregnant - about 12 weeks gestat|on at the t|me of presentat|on. G10
Asymptomat|c. |anned pregnancy.

She was noted by her G to be pa|e when she went for her U1. She does not
reca|| any fam||y members who are pa|e or requ|re regu|ar transfus|on. ner
menses pr|or to pregnancy was unremarkab|e. She eats ||ke a true Ma|ays|an w|th
a "see food, eat food" d|et. No b|eed|ng noted.

C||n|ca||y she appears pa|e but no ko||onych|a or g|oss|t|s |s noted. She |s not
[aund|ced or sa||or or have any abnorma| fac|es. No sp|enomega|y.

ner |n|t|a| fu|| b|ood count from her G showed a m|crocyt|c, hypochrom|c
anaem|a (MCn, 2S.6 pg]ce||, MCV 68) w|th a haemog|ob|n of 10.2 g]dL. 1he G had
started ferrous su|phate tab|ets at 200 mg three t|mes da||y for 4 weeks and asked
for a repeat fu|| b|ood count when the tab|ets had f|n|shed. 1he repeat fu|| b|ood
count resu|ts show a deter|orat|on of the anaem|a as be|ow.

naemog|ob|n 9.8: |ate|ets: 384
Wh|te ce|| count: 10100 MCn: 26 MCV 6S

At th|s po|nt the G asked for a consu|t.

uest|ons
- Why d|d the |ron tab|ets not he|p?
- What |s the s|gn|f|cance of th|s resu|t?
- now m|ght you exp|a|n the d|fferent resu|ts for the two fu|| b|ood counts?

What w||| you do now for th|s pat|ent?
rof : uear yln llng,
dleLary lron comes ln dlfferenL forms, Lhe percenLage of dleLary lron absorbed
depends on Lhe Lype of food we eaL and whaL oLher foods are belng eaLen aL Lhe
same Llme. lor example, lron from meaL ls easler for Lhe body Lo absorb Lhan lron
from vegeLable.
ln addlLlon, lron absorpLlon can be greaLly lncreased or decreased by varlous facLors.
Chemlcals called polyphenols ln Lea, coffee, cocoa, splnach lnhlblL lron absorpLlon as
well. LaLlng more ascorblc acld, whlch ls common ln frulLs, vegeLables and forLlfled
foods, can lmprove lron absorpLlon. 8uL Calclum lnhlblLs Lhe absorpLlon of lron by an
unknown mechanlsm. 1hls ls probably why Lhere ls a correlaLlon beLween hlgh mllk
lnLake and lron deflclency.

lf lndeed Lhls paLlenL or any paLlenL has le def, Lhen Lhey should have lron
supplemenLaLlon boLh Lo correcL anaemla and replenlsh body sLores. 1hls ls
achleved mosL slmply and cheaply wlLh ferrous su|phate 200 mg three t|mes da||y
a|though ferrous g|uconate and ferrous fumarate are as effect|ve.

LlemenLal lron ls Lhe lron avallable ln Lhe supplemenL for absorpLlon

Ascorblc acld enhances lron absorpLlon and can be glven LogeLher.
aLlenLs ofLen ask for ln[ecLlons lnsLead! 8uL arenLeral lron should only be used
when Lhere ls Lrue lnLolerance Lo oral preparaLlons. lL ls palnful (when glven
lnLramuscularly), expenslve, cause Lhe bum Lo have a 8LACk spoL and may cause
anaphylacLlc reacLlons. Anu 1he rlse ln haemoglobln ls no qulcker Lhan wlLh oral
preparaLlons!!! So why Lake Lhe rlsk! 1he haemog|ob|n concentrat|on shou|d r|se by
2 g]d| after 3-4 weeks.
lron from meaL, poulLry, and flsh (l.e., heme lron) ls absorbed Lwo Lo Lhree Llmes
more efflclenLly Lhan lron from planLs (l.e., non-heme lron).
1he amounL of lron absorbed from planL foods (non-heme lron) depends on Lhe
oLher Lypes of foods eaLen aL Lhe same meal. 1haLs why we eaL a mlxLure of
dlshes.loods conLalnlng heme lron (meaL, poulLry, and flsh) enhance lron absorpLlon
from foods LhaL conLaln non-heme lron (e.g., forLlfled bread, splnach).

loods conLalnlng vlLamln C also enhance non-heme lron absorpLlon when eaLen aL
Lhe same meal. lrulLs aL end of meal ls lmporLanL.
SubsLances (such as polyphenols, phyLaLes, or calclum) LhaL are parL of some foods
or drlnks such as Lea, coffee, whole gralns, legumes and mllk or dalry producLs can
decrease Lhe amounL of non-heme lron absorbed aL a meal. urlnk Chlnese Lea ln
small amounLs durlng your meal, good Lea ls slpped rlghL?! noL gulped.
Calclum decrease Lhe amounL heme-lron absorbed aL a meal. Powever, for healLhy
lndlvlduals who consume a varleLy of food, Lhe amounL of lron lnhlblLlon from Lhese
subsLances ls usually noL of concern.

vegeLarlan dleLs are low ln heme lron.

Medlclnes for pepLlc ulcer dlsease and acld reflux Laken long Lerm llke some poor
Leachers here for chronlc sLress lnduced gasLrlLls reduce Lhe amounL of acld ln Lhe
sLomach and Lhe lron absorbed and cause lron deflclency. 1haLs Lhe prlce we pay for
Leachlng!
1hls case scenarlo ls compllcaLed by Lhe facLs LhaL

1. She ls pregnanL
2. She ls noL mensLruaLlng

8ecause of rapld growLh, lnfanLs and Loddlers need more lron Lhan older chlldren. A
sLudenL above ls worrled abouL Lhe paraslLe called AncylosLoma duodenale. l am
more concerned abouL a MuCP2 blgger paraslLe called lCL1uS! Women who are
pregnanL have hlgher lron needs because of Lhls. 1o geL enough, mosL women musL
Lake an lron supplemenL ln pregnancy.

Serum lron. 1hls LesL measures Lhe amounL of lron ln Lhe blood. 8u1 1he level of
lron ln Lhe blood may be normal even lf Lhe LoLal amounL of lron ln Lhe body ls low.
lor Lhls reason, a serum lron LesL ls noL adequaLe.

Serum ferrlLln. lerrlLln ls a proLeln LhaL helps sLore lron ln Lhe body. lLs a 8lC magneL
LhaL sLlcks many le molecules buL lLs also an lnflammaLlon assoclaLed molecule.
8emember CyLoklne sLorm ln uengue and whaL we musL measure? Se lL88l1ln!!!!
A measure of Lhls proLeln ln Lhe serum helps flnd ouL how much of Lhe body's sLored
lron has been used or lefL. Se ferrlLln reflecLs Lhe LoLal body ferrlLln values.

1ransferrln level, and LoLal lron-blndlng capaclLy. 1ransferrln ls a proLeln LhaL carrles
lron ln Lhe blood. lLs llke Lhe lorrles LhaL carry Lhls heavy meLal round and round
wlLhouL lL falllng off and damaglng all Lhe roads. 1oLal lron-blndlng capaclLy
measures how much ls Lhe LoLal capaclLy of Lhe Lransferrln ln Lhe blood ls Lhere Lo
carry lron. lf Lhe paLlenL has lron-deflclency anemla, he/she wlll have a hlgh level of
Lransferrln, a hlgh 1oLal le carrylng capaclLy aka 1l8C LhaL has lronlcally no lron.
(hehe l8Cnlcally)

So whaL should we use for screenlng, and whaL do we use when Lrylng Lo dlagnose a
cause of anaemla?
Ior G screen|ng, se ferr|t|n |s eas||y ava||ab|e and affordab|e. Ior d|agnost|c work
up, the |ron stud|es LUS Io||c ac|d |eve|s LUS V|t 812 and 1Sn |s needed. 1he
most usefu| Ix at workup |s actua||y a 8I read by a competent haemato|og|st. 1he
answer |s a|most a|ways there.
Pemoslderln ls an abnormal mlcroscoplc plgmenL composed of lron oxlde and can
accumulaLe ln dlfferenL organs ln varlous dlseases. lron ls Loxlc when noL properly
sLored. Pumans sLore lron wlLhln ferrlLln. 1he form of lron ln ferrlLln ls lron(lll) oxlde-
hydroxlde. 8y complexlng wlLh ferrlLln, Lhe lron ls made waLer soluble!

Several dlseases resulL ln deposlLlon of lron(lll) oxlde-hydroxlde ln Llssues ln an
lnsoluble form. 1hese deposlLs of lron ls hemoslderln! 1hese deposlLs ofLen cause no
sympLoms, buL Lhey lead Lo organ damage.

Pemoslderln ofLen forms afLer bleedlng lnLo an organ. When blood leaves a
rupLured blood vessel, Lhe hemoglobln of Lhe red blood cells ls released lnLo Lhe
exLracellular space. 1he macrophages phagocyLose Lhe hemoglobln Lo degrade lL,
produclng hemoslderln and porphyrln. 1he lron ln haemoslderln cannoL be released
for use. lLs sLuck!

?L: afLer a monLh's LreaLmenL wlLh lron supplemenL and assumlng she ls Laklng her
lron LableLs, she ls sLlll havlng mlcrocyLlc hypochromlc anemla wlLh an MCv of 63,
MCP of 26, low normal MCPC, normal 88C and normal 8uW! We don'L know Lhe Se
lerrlLln and 1l8C nor serum lron so far.

8uW ls a quanLlLaLlve measuremenL of anlsocyLosls on 8l. lL Lells us LhaL Lhe 88C
producLlon ls haywlred and a hlgh 8uW reflecLs a nuLrlLlonal anemla. 8uW helps us
dlfferenLlaLe Lhalassemla and luA for mlcrocyLlc anemla, and vlLamln 812/folaLe
deflclency (megaloblasLlc anemla) from oLher macrocyLlc buL nCn megaloblasLlc
anemla, hence lLs lmporLance. ln Lhalassemla Lhe producLlon of 88C ls generally sLlll
CkA?, alLhough Lhey are ablL small, hence Lhe normal 8uW.

ln Lhls paLlenL, a normal 88C and low normal MCPC, coupled on wlLh a normal 8uW,
we really couldn'L sLrlke Lhalasemla off, moreover she's pregnanL!

So ln vlew of a mlcrocyLlc hypochromlc anemla LhaL ls noL correcLable and also a l8C
componenLs whlch suggesL someLhlng oLher Lhan luA, l would run lron panel LesLs
Lo correcL whaLever lron deflclency anemla Lhere ls, and proceed Lo work her up for
Lhalasemla. 8eLa 1halassemla LralL can be easlly plck up by Pb elecLrophoresls, whlle
alpha Lhal needs a molecular dlagnosls (as all Pb has an alpha componenL, on
elecLrophoresls one low all low!)
lL ls lmporLanL Lo plck up alpha Lhal, a dlsease LhaL ls caused by gene deleLlon. lf Lhls
paLlenL happened Lo be a carrler/ mlnor, lL ls even more lmporLanL Lo screen her
husband Loo! Lhe scarlesL Lhlng abouL alpha Lhal ls for Lhe moLher Lo have an aa/- -
gene makeup whlch have Lhe llkellhood Lo couple up wlLh a slmllar aa/- - gene
makeup carrled by her husband.............and produce a hydrops ln her pregnancy.

rof : 1he normal physlologlcal lncrease ln plasma volume ln pregnancy causes
haemodlluLlon and can glve an arLlflclally low haemoglobln level. Powever,
haemog|ob|n |eve|s shou|d not fa|| be|ow 11.0g]dL and |ess than 10.Sg]dL |s
abnorma|.

We ofLen ASSuML LhaL a mlcrocyLlc, hypochromlc anaemla esp ln pregnancy ls
caused by a lack of lron. Powever, Lhls paLlenL ls noL lron deflclenL. Per se ferrlLln
when LesLed ls normal. 1halassaemla carrlers are well, normal looklng people buL ln
females wlLh heavy menses or durlng pregnancy are ofLen anaemlc, sharlng Lhe
feaLures of lron deflclency of mlcrocyLosls and hypochromla. A carefu| |ook beyond
the I8C at the 8I w||| te|| us the answer because the 8I |s very character|st|c.
Another d|st|ngu|sh|ng e|ement |s the erythrocyte count wh|ch |s reduced w|th
|ron def|c|t, but often |ncreased |n tha|assaem|a carr|ers.

Per parLner/husband/boyfrlend needs urgenL LesLlng for haemogloblnopaLhles ln
order Lo esLlmaLe Lhe rlsk Lo Lhe feLus. lf Lhe parLner LesLs poslLlve Lhe couple can be
offered feLal LesLlng Lo deLermlne how Lhe chlld mlghL be affecLed, as for Lhe feLus
Lhere ls a one ln Lwo chance of belng a carrler of haemogloblnopaLhy and a one ln
four chance of belng elLher affecLed by Lhe dlsease or free of Lhe geneLlc dlsposlLlon.
Lxcludlng Lhe posslblllLy LhaL Lhe baby's faLher ls a carrler of a haemogloblnopaLhy
allows everyone Lo relax.

A very |ow MCV]MCn must tr|gger test|ng for haemog|ob|nopath|es.




kL? Cln1S
- WaLch ouL: noL all mlcrocyLlc, hypochromlc anaemlas as seen ln Lhe l8C ls caused
by lron deflclency.

- 1esL resulLs ln pregnancy have a dlfferenL slgnlflcance compared wlLh LesLs for
Lhose noL pregnanL.
lor one you Lhe docLor ls deallng wlLh a few llves!

rof : 1he paLhogenesls of anemla of chronlc dlsease ls mulLlfacLorlal and ls relaLed
Lo hypo-act|v|ty of the bone marrow, w|th re|at|ve|y |nadequate product|on of
erythropo|et|n or a poor response to erythropo|et|n, as we|| as s||ght|y shortened
red b|ood ce|| surv|va|.

1he hallmark ferroklneLlc proflle of anem|a of chron|c d|sease |s decreased serum
|ron |eve|, decreased transferr|n |eve|, or norma| or e|evated ferr|t|n |eve|s, a|| of
wh|ch resu|t |n |ron be|ng present but |naccess|b|e for use.

uo noL forgeL Lndocrlne deflclency sLaLes, lncludlng hypothyro|d|sm, adrena| or
p|tu|tary |nsuff|c|ency, and hypogonad|sm, wh|ch may cause secondary bone
marrow fa||ure because of reduced st|mu|at|on of erythropo|et|n secret|on.
nyperthyro|d|sm may a|so cause normocyt|c anem|a.

Anemla occurs ln acuLe and chronlc renal fallure. 1he anem|a |s usua||y normocyt|c
but may be m|crocyt|c. In rena| fa||ure, anem|a occurs |n part because urem|c
metabo||tes decrease the ||fespan of c|rcu|at|ng red b|ood ce||s and reduce
erythropo|es|s.

Anemla secondary Lo uremla ls characLerlzed by |nappropr|ate|y |ow erythropo|et|n
levels, ln conLrasL Lo Lhe normal or hlgh levels LhaL occur wlLh mosL oLher causes of
anemla. 1o furLher confuse Lhe presenLaLlon, serum lron levels and Lhe percenLage
of lron saLuraLlon are ofLen low. lurLhermore, Lhe serum creaLlnlne level and Lhe
degree of anemla may noL correlaLe well.

And never forget abt kL1ICULCC1LS! ! 1hey fa|se|y |ncrease mcv.

8emember LhaL Lhe role of Lhe consulLanL ls 1C 8L CCnSuL1Lu WPLn C1PL8S
PAvL ullllCuL1? SCLvlnC A uZZLL. So one musL Lhlnk laLerally. When Lhe PC or
MC ls sLuck lL ls usually because Lhey are Lhlnklng along one llne and nC1 SLLlnC
1PL lC8LS1. !uS1 1PL 18LL
rof: ?ln Llng,

ou know that |n tha|assem|a m|nor]tra|t, pat|ents tend to have e|evated k8C
count (>S.S) w|th |ow mcv and mch.

What |s the pathophys|o|ogy beh|nd th|s? What does th|s |ead to c||n|ca||y?
When a pat|ent has a type of tha|assem|a, there |s an excess product|on and
accumu|at|on of g|ob|n cha|ns produced by genes that are not effected by the
tha|assem|a de|et|on. 1h|s |s a compensat|on mechan|sm that the body ut|||zes to
ma|nta|n hemog|ob|n product|on.

Ior eg In a|pha tha|assem|a, the body can produce excess gamma cha|ns as a
compensatory mechan|sm. 1h|s can |ead to the product|on of gamma cha|n
tetramers (hemog|ob|n 8art's) |n the unborn ch||d and as beta cha|n tetramers
(hemog|ob|n n) |n adu|ts. 1h|s subsequent tetramer accumu|at|on |n response to
tha|assem|a often |eads to red b|ood ce|| damage and hemo|yt|c anem|a.
1he norma| or h|gh k8C count resu|ts from MASSIVL IAC1CkILS |n bone marrow
produc|ng k8Cs desperate|y |n response to chron|c anaem|a.
1ogeLher wlLh Lhe decreased MCv Lhls are lndlcaLors of lneffecLlve eryLhropoelsls.

1he k8C morpho|ogy shows hypochrom|c m|crocytos|s w|th sch|stocytes, target
ce||s, an|sopo|k||ocytos|s and basoph|||c st|pp||ng. Sch|stocytes form by severa|
mechan|sms, one be|ng the remova| of k8C |nc|us|ons.

1he splenomegaly ls conslsLenL wlLh lncreased 88C desLrucLlon.
|n ||ng,
|s remember the fo||ow|ng ru|es:
(1) 1ha| tra|t rare|y causes anem|a of |ess than 10 g]dL.

(2) 1he k8C count |n 11 |s more than S.0 x 106]L (S.0 x 1012]L) and |n IDA |s |ess
than S.0 x 106]L (S.0 x 1012]L).

(3) 1he kDW |n IDA |s more than 17 and |n 1ha|assaem|a 1ra|t |s |ess than 17.

8U1 1nL MCS1 IM1 AND SIMLL 1LS1 IS A 8I!

In 1ha|assaem|a 1ra|t |t |ooks ||ke a 2CC w|th a|| the var|ous ce||s noted above. In
IDA the k8Cs are ||ke M|n|ons.... ALL SMALL ALL AND CU1L. As |ron-def|c|ency
anem|a progresses, and the pat|ent's serum |ron drops |ower and |ower, each
success|ve wave of new red ce||s gets sma||er and sma||er.

So there are some k|nd of sma|| ce||s, and some rea||y sma|| ce||s! Sma||er and
sma||er m|n|ons as each batch |s re|eased. 1he red ce|| d|str|but|on w|dth (kDW) |s
h|gh |n |ron def|c|ency anem|a because there |s now a w|de var|at|on |n red ce||
s|ze.

In m||d tha|assem|a (a|pha or beta), the red ce||s are a|| about the same s|ze, wh||e
they are we|rd |ook|ng they are |n every batch s|m||ar|y we|rd! ! nence there |s
v|rtua||y m|n|ma| var|at|on. So the kDW |s norma|.

1h|s d|fference |n kDW |s he|pfu| when you're try|ng to d|fferent|ate IDA and
tha|assem|a, |f you have a m|crocyt|c, hypochrom|c anem|a, the next th|ng you'd
do |s |ook at the kDW (and p|s3 |ook at the b|ood smear).

If the kDW |s norma| (the ce||s are most|y the same s|ze), then |t's probab|y
tha|assem|a. If the kDW |s h|gh (the ce||s vary a |ot |n s|ze), then |t's probab|y |ron
def|c|ency anem|a.
6) on GkCSSL DAMAGLD SMALL ICIN1S CI 1nL nANDS
Dear y|n ||ng,

1here |s an e|der|y |ady who came to me w|th gross|y damaged sma|| [o|nts of both
hands. Symmetr|ca|. Mark ventra| sub|uxat|on of both hands at the wr|st [o|nts |s
seen. 1here |s a|so prom|nent u|nar dev|at|on |n both hands and her f|ngers |ook
sma|| and f|a||.

1here |s no warmth or swe|||ng by the t|me I saw her.
ner f|ngerna||s have onycho|ys|s. 1he rest of her sk|n |s norma|.
ner knees, feet and h|ps are norma|. ner e|bows cannot be fu||y extended.
ner b|ood tests do not show any ev|dence of |nf|ammat|on. kA factor negat|ve.
What are your thoughts?
uoes 8CAuS mean anyLhlng?
rof : sorlaLlc arLhrlLls usually occurs wlLh skln psorlasls. eople wlLh psorlasls may
also have changes ln Lhelr flngernalls and Loenalls, such as nalls LhaL become plLLed
or rldged, crumble, or separaLe from Lhe nall beds. Slgns and sympLoms of psorlaLlc
arLhrlLls lnclude sLlff, palnful [olnLs wlLh redness, heaL, and swelllng ln Lhe
surroundlng Llssues. When Lhe hands and feeL are affecLed, swelllng and redness
may resulL ln a "sausage-llke" appearance of Lhe flngers or Loes (dacLyllLls). In most
peop|e w|th psor|at|c arthr|t|s, psor|as|s appears before [o|nt prob|ems deve|op.
sor|as|s typ|ca||y beg|ns dur|ng ado|escence or young adu|thood, and psor|at|c
arthr|t|s usua||y occurs between the ages of 30 and S0. Powever, boLh condlLlons
may occur aL any age.
ln a small number of cases, psorlaLlc arLhrlLls develops ln Lhe absence of noLlceable
skln changes.

sorlaLlc arLhrlLls may be dlfflculL Lo dlsLlngulsh from oLher forms of arLhrlLls,
parLlcularly when skln changes are mlnlmal or absenL. Na|| changes and dacty||t|s
are two features that are character|st|c of psor|at|c arthr|t|s, a|though they do not
occur |n a|| cases.

sor|at|c arthr|t|s |s categor|zed |nto f|ve types:
(D)d|sta| |nterpha|angea| predom|nant,
(C)asymmetr|c o||goart|cu|ar,
(k)symmetr|c po|yarthr|t|s,
(S)spondy||t|s, and
(A)arthr|t|s mut||ans.
now yln llng pls makes a word wlLh Lhese caplLal leLLers llke how nLlS ls made lnLo
SlnL.
kCADS!

1he d|sta| |nterpha|angea| predom|nant type affecLs malnly Lhe ends of Lhe flngers
and Loes llke SLL. Na|| changes are espec|a||y frequent wlLh Lhls form of psorlaLlc
arLhrlLls.

1he asymmetr|c o||goart|cu|ar and symmetr|c po|yarthr|t|s types are the most
common forms of psor|at|c arthr|t|s. 1he asymmeLrlc ollgoarLlcular Lype of psorlaLlc
arLhrlLls lnvolves dlfferenL [olnLs on each slde of Lhe body, whlle Lhe symmeLrlc
polyarLhrlLls form affecLs Lhe same [olnLs on each slde llke 8A. Any [olnL ln Lhe body
may be affecLed ln Lhese forms of Lhe dlsorder, and sympLoms range from mlld Lo
severe.

Some lndlvlduals wlLh psorlaLlc arLhrlLls have [olnL lnvolvemenL LhaL prlmarlly
lnvolves spondyllLls. SympLoms of Lhls form of Lhe dlsorder lnvolve paln and sLlffness
ln Lhe back or neck, and movemenL ls ofLen lmpalred. !olnLs ln Lhe arms, legs, hands,
and feeL may also be lnvolved.

1he mosL severe and leasL common Lype of psorlaLlc arLhrlLls ls called arthr|t|s
mut||ans. Iewer than S percent of |nd|v|dua|s w|th psor|at|c arthr|t|s have th|s
form of the d|sorder, UNICk1UNA1LL th|s pat|ent has th|s. ner c|ue was |n her
extens|ve na|| changes not seen |n kA.
ArLhrlLls muLllans lnvolves severe lnflammaLlon LhaL damages Lhe [olnLs ln Lhe hands
and feeL, resulLlng ln deformaLlon and movemenL problems. 8one loss (osLeolysls) aL
Lhe [olnLs may lead Lo shorLenlng (Lelescoplng) of Lhe flngers and Loes. neck and
back paln may also occur buL Lhankfully she was spared.

Pow common ls psorlaLlc arLhrlLls?

8etween S and 20 percent of peop|e w|th psor|as|s deve|op psor|at|c arthr|t|s.
Some suggesL a flgure as hlgh as 30 percenL. sorlasls lLself ls a common dlsorder,
affecLlng approxlmaLely 2 Lo 3 percenL of Lhe populaLlon worldwlde.

Lxam C.... WhaL genes are relaLed Lo psorlaLlc arLhrlLls?

1he speclflc cause of psorlaLlc arLhrlLls ls unknown. lnflammaLlon occurs when Lhe
lmmune sysLem sends slgnallng molecules and whlLe blood cells Lo a slLe of ln[ury or
dlsease Lo flghL mlcroblal lnvaders and faclllLaLe Llssue repalr. When Lhls has been
accompllshed, Lhe body ordlnarlly sLops Lhe lnflammaLory response Lo prevenL
damage Lo lLs own cells and Llssues. Mechanlcal sLress on Lhe [olnLs, such as occurs
ln movemenL, may resulL ln an excesslve lnflammaLory response ln people wlLh
psorlaLlc arLhrlLls. 1he reasons for Lhls excesslve lnflammaLory response are unclear.
Changes ln several genes LhaL may lnfluence Lhe rlsk of developlng psorlaLlc arLhrlLls.
1he mosL well-sLudled of Lhese genes belong Lo a famlly of genes called Lhe human
leukocyLe anLlgen (PLA) complex. 1he PLA complex helps Lhe lmmune sysLem
dlsLlngulsh Lhe body's own proLelns from proLelns made by forelgn lnvaders. Lach
PLA gene has many dlfferenL normal varlaLlons, allowlng each person's lmmune
sysLem Lo reacL Lo a wlde range of forelgn proLelns. varlaLlons of several PLA genes
seem Lo affecL Lhe rlsk of developlng psorlaLlc arLhrlLls, as well as Lhe Lype, severlLy,
and progresslon of Lhe condlLlon.

now ln Lhe CSCL slLuaLlon, afLer you had dlagnosed whaL assessmenL musL follow?
1hls ls Lhe crlLlcal parL. Any docLor worLh hls her salL can dlagnose buL Lhe M8C
wlnner musL have Lhls cruclal nexL sLep. l wlll fall Lhe candldaLe lf Lhls ls noL done
properly.
When the MC I and DI are a|| |nvo|ved th|nk of psor|at|c arthropathy
When there |s arthr|t|s and funny na||s th|nk of |t too.
When the hands are ||tera||y destroyed th|nk of |t too. kA destruct|on has the
c|ass|c features. 1h|s |ooks ||ke |ts nuked.

uear yln llng
?our answer ls good for membershlp exam buL sLlll lncompleLe.
8emember l Lrled so very hard Lo Leach Lhe 4 aspecLs of dlagnosls. WhaL are Lhey?
uncle klan seng added Lhe 3Lh aspecL whlch ls C8uClAL Lo flylng aL M8C exams!

1hls ls Lhe emoLlonal Loll of psorlaLlc arLhrlLls! Cn Lop of evaluaLlon of funcLlon.

Whlle mosL chronlc lllnesses lncrease sLress, Lhe emoLlonal Loll of psorlaLlc arLhrlLls
can very hlgh. noL only do paLlenLs wlLh psorlaLlc arLhrlLls feel embarrassed because
of Lhe skln psorlasls, buL Lhe [olnL paln, sLlffness, and faLlgue make lL near lmposslble
Lo feel poslLlve and be acLlve.
nPS guldance on psorlaLlc arLhrlLls Lells docLors Lo screen paLlenLs for emoLlonal
problems! !! never forgeL Lhese 2 Lhlngs, IUNC1ICN AND LMC1ICN. ln Lhe ldeal
world Lhls of course would apply for all paLlenLs of all lllnesses.
?L : 4 aspecLs of dlagnosls ls Anatom|ca|, patho|og|ca|, aet|o|og|ca| and funct|ona|.
Sth one wou|d be emot|ona|.
rof: Dr Dav|d kL uek reporLs a paLlenL worLh a lesson Lo all of us
A few years ago a 74 yr old man wlLh exLenslve psorlasls buL moderaLe polyarLhrlLls
presenLed wlLh S1LMl and acuLe pulmonary edema. We LreaLed hls acuLe hearL
fallure Lhen sLenLed Lhe culprlL arLery of hls 3 vessel CAu. 1hen we goL on Lo Lalklng
abouL hls skln and [olnL dlsease and was shocked Lo hear LhaL he'd noL venLured ouL
of hls home for 3 years because of shame over hls prevlously unLreaLable and 'ugly'
skln condlLlon! We goL a dermaLologlsL ln who flnally managed Lo geL hls psorlasls
under conLrol!
Pere for M8C candldaLes Lo remember ls LhaL someone wlLh a chronlc
lnflammaLory dlsorder can be predlsposed Lo a hlgher rlsk of CAu. MeLhoLrexaLe
when used ln LreaLlng psorlasls also predlsposes Lhe paLlenL Lo hlgher LhromboLlc
evenLs. So you absoluLely rlghL LhaL we need Lo more rouLlnely gauge assess Lhe
emoLlonal and psychologlcal componenLs and needs lf our paLlenLs!


7) on 8AD 1CNSILS!
Dear |n L|ng,

A 17-year-o|d schoo| g|r| came w|th her mother. Cne week prev|ous|y she had
been seen by a G and was d|agnosed w|th acute tons||||t|s. 1he doctor noted a
h|story of sore throat, ma|a|se, musc|e aches a|| over the body, sh|ver|ng, swe|||ng
around the eyes and headaches. ner mother was very anx|ous as she wants her
we|| asap to study!

1he exam|nat|on then revea|ed a temperature of 39.6C, pharyng|t|s, red, puru|ent
and en|arged tons||s, and cerv|ca| |ymphadenopathy. 1he doctor prescr|bed a S-
day course of amp|c||||n and adv|sed the pat|ent to |ncrease her f|u|d |ntake, rest
and take regu|ar panado|.

1he mother |s concerned because her daughter has not recovered. She angr||y
re|ated that at f|rst the ant|b|ot|cs seemed to he|p and the temperature, sore
throat and headaches |mproved. 8ut after 4 days a fa|nt non-|tchy red rash
deve|oped.
Wh||e the pa|n |n the throat |s better, the pat|ent comp|a|ns of more pa|ns |n her
neck and the recurrence of headaches. She fee|s tota| |ack of energy and mother |s
concerned that her daughter s|eeps 18 hours a day. Mother |s concerned about not
hav|ng the energy to study for her upcom|ng exams.

Cn exam|nat|on she |ooks pa|e, unwe|| w|th a s||ght|y ye||ow sc|era. ner
temperature |s 37.6C. 1here are mu|t|p|e swo||en and tender |ymph nodes |n the
anter|or and poster|or cerv|ca| reg|ons, b||atera||y. ner throat |s st||| |nf|amed, and
the tons||s en|arged, but w|thout wh|te patches. Some petech|ae |s seen on the
soft pa|ate. 1here |s a fa|nt red macu|ar rash a|| over her trunk spread|ng to the
||mbs. 1he t|p of the sp|een |s pa|pab|e on deep |nsp|rat|on, the ||ver 2 I8 pa|pab|e.


- What |s the ||ke|y d|agnos|s and d|fferent|a| d|agnos|s?
- What tests wou|d you order?
What w||| you do wh||e awa|t|ng the b|ood tests?
rof: CfLen Lhe cervlcal Lns ls 8lC and parenLs worry abouL a mallgnancy. lf Lhe
Lonslls look as Lhough a madman had palnLed whlLewash on lL, l am reasonably
confldenL but |f tons||s are m||d|y |nf|amed and w|th LNs and hepatosp|enomega|y,
I too worry about an Acute naemato|og|ca| patho|ogy. A 8I |s very usefu|, often
an exper|enced atho|og|st w||| p|ck up Infect|ous Mononuc|eos|s.
lM aka Clandular fever ls Lhe mosL llkely cllnlcal dlagnosls as many of you all
reallsed. AcuLe LonsllllLls ls seen far more commonly ln prlmary care and would have
been a dlsease suscepLlble Lo anLlbloLlc LreaLmenL alLhough the rash may have been
tr|ggered by the ant|b|ot|c or may be from the |||ness |tse|f. 1he furLher llsL of
poLenLlal dlagnoses lncludes acute numan |mmunodef|c|ency v|rus (nIV) |nfect|on,
o|d fr|end d|phther|a, cytomega|ov|rus and |eukaem|a.


1he au|-8unne|| react|on (Monospot) - heLerophlle lmmunoglobulln M (lgM)
anLlbodles aggluLlnaLlng sheep eryLhrocyLes - ls Lhe mosL commonly used screenlng
LesL for glandular fever. It can be fa|se|y negat|ve, espec|a||y |n young pat|ents, or
fa|se|y pos|t|ve, for examp|e ow|ng to cytomega|ov|rus, so lLs noL very good.

A fu|| b|ood count shou|d show a |eucocytos|s between 10000 and 20000
ce||s]mm3, thrombocytopen|a (often), and on the b|ood f||m many atyp|ca|
act|vated 1-|ymphocytes (mononuc|eos|s ce||s). More than 20 per cent atyp|ca|
|ymphocytes or more than S0 per cent |ymphocytes w|th at |east 10 per cent
atyp|ca| |ymphocytes on b|ood f||m make the d|agnos|s very ||ke|y.


1here are more speclflc lmmunologlcal LesLs for LpsLeln-8arr vlrus avallable whlch
can be useful lf Lhe aul-8unnell LesL ls negaLlve and we sLlll suspecL Lhe dlsease buL
lLs academlc because by Lhe Llme Lhe resulLs are back lLs already recovery Llme.

Clandular fever (lnfecLlous mononucleosls, or klsslng dlsease) ls an lnfecLlon of Lhe
8-lymphocyLes by Lhe LpsLeln-8arr vlrus. lL ls a self-llmlLlng dlsease. 1he vlrus ls
secreLed ln Lhe sallva and can be LransmlLLed Lhrough klsslng or sharlng uLenslls
(cups, cuLlery, Lowels).

1he organlsm may also be shed from Lhe uLerlne cervlx, lmpllcaLlng Lhe role of
genlLal Lransmlsslon ln some cases and posslbly Cral Sex! Cn rare occaslon, L8v ls
spread vla blood Lransfuslon.

1he lncubaLlon perlod ls 4-8 weeks. Most pat|ent recover w|th|n 2 weeks w|th
some res|dua| t|redness for another week. nowever, a s|gn|f|cant m|nor|ty go on to
suffer w|th t|redness for much |onger.

lL ls reassurlng Lo Lhe docLor, paLlenL and relaLlves Lo have Lhe dlagnosls conflrmed.
She needs to avo|d contact sport because of the potent|a| for damage to her
swo||en sp|een, for 1-2months. She shou|d see herse|f as |nfect|ous wh||e she |s
fee||ng unwe||, avo|d|ng shar|ng utens||s and c|ose bod||y contact.

kL? Cln1S
- Larly presenLaLlons of dlsease can be decepLlve, wlLh Lhe correcL dlagnosls
emerglng laLer ln lLs progresslon.
- roper dlagnosls and senslble advlce are reassurlng for Lhe paLlenL and Lhelr
famlly, wheLher or noL Lhere ls effecLlve medlcal LreaLmenL as Lhe dlfferenLlals are
noL Loo nlce folks.

uear ?ln Llng,

ClrculaLlng 8 cells spread Lhe lnfecLlon LhroughouL Lhe enLlre reLlcular endoLhellal
sysLem (8LS), le, llver, spleen, and perlpheral lymph nodes. 1haLs why Lhey are
Lnlarged!! Lasy Lo remember.

L8v lnfecLlon of 8 lymphocyLes resulLs ln a humora| and ce||u|ar response Lo Lhe
vlrus. 1he humoral lmmune response dlrecLed agalnsL L8v sLrucLural proLelns ls Lhe
basls for Lhe LesL used Lo dlagnose L8v lnfecLlous mononucleosls. Powever, Lhe 1-
lymphocyLe response ls essenLlal ln Lhe conLrol of L8v lnfecLlon, natura| k|||er (Nk)
ce||s and predom|nant|y CD8+ cytotox|c 1 ce||s contro| pro||ferat|ng 8 |ymphocytes
|nfected w|th L8V.

In nIV pat|ents we can we|| understand why the L8V goes berserk!

1he 1-lymphocyLe cellular response ls crlLlcal ln deLermlnlng Lhe cllnlcal expresslon
of L8v vlral lnfecLlon. A rapld and efflclenL 1-cell response resulLs ln conLrol of Lhe
prlmary L8v lnfecLlon and llfelong suppresslon of L8v.

Ineffect|ve 1-ce|| response may resu|t |n excess|ve and uncontro||ed 8-ce||
pro||ferat|on, resu|t|ng |n 8-|ymphocyte ma||gnanc|es (eg, 8-ce|| |ymphomas).

1he |mmune response to L8V |nfect|on |s fever, wh|ch occurs because of cytok|ne
re|ease consequent to 8-|ymphocyte |nvas|on by L8V. Lymphocytos|s observed |n
the kLS |s caused by a pro||ferat|on of L8V-|nfected 8 |ymphocytes. 1hats why the
|ymphocyte count goes up and you have funny |ook|ng ce||s. At |east to me |a)

harynglLls observed ln L8v lnfecLlous mononucleosls ls caused by Lhe prollferaLlon
of L8v-lnfecLed 8 lymphocyLes ln Lhe lymphaLlc Llssue of Lhe oropharynx. now you
know why Lhe Lonslls whlch ls effecLlvely 2 8lg Lns look llke a warzone.

earls:
fat|gue |s a|most |nvar|ab|e! |s note th|s symptom.

u|monary |nvo|vement |s not a prom|nent feature of L8V |nfect|ous
mononuc|eos|s. If the pat|ent |s bad|y hack|ng h|s] her |ungs away, I1S NC1 IM!

Iaund|ce occurs because of the hepat|t|s.

|s note y|n ||ng that a CSI1IVL 1nkCA1 C&S for Strep may mean NC1nING! as
approx|mate|y 30 of pat|ents w|th L8V |nfect|ous mononuc|eos|s have group A
streptococca| carr|age of the oropharynx. 1he unwary phys|c|an may |ncorrect|y
conc|ude that a throat cu|ture for group A streptococc| |n a pat|ent w|th |nfect|ous
mononuc|eos|s represents streptococca| pharyng|t|s.

L8V |nfect|ous mononuc|eos|s |s character|zed by ear|y and trans|ent b||atera|
upper-||d edema but th|s |s not a common s|gn. 1he externa| eye |nvo|vement of
L8V |nfect|ous mononuc|eos|s |s character|zed by b||atera| upper-||d edema. 1h|s |s
referred to as noag|and s|gn.
Poagland slgn may be deLecLed when paLlenLs look ln Lhe mlrror early ln Lhe course
of Lhelr lllness or when Lhe asLuLe physlclan noLlces Lhls early ln Lhe cllnlcal
presenLaLlon. noag|and s|gn |s present for on|y the f|rst few days of |||ness and
shou|d not be sought |ater |n the course of the |nfect|ous process.

L8V |s the ma|n cause of ma||gnant 8-ce|| |ymphomas |n pat|ents rece|v|ng organ
transp|ants. 1he Immunosuppress|on |s neaven for the v|rus!
uependlng on Lhe lnLenslLy, rapldlLy, and compleLeness of Lhe 1-lymphocyLe
response, mallgnancy may resulL lf L8v-lnduced 8-lymphocyLe prollferaLlon ls
unconLrolled. Podgkln dlsease and non-Podgkln lymphoma (nPL) may resulL. CLher
L8v-relaLed mallgnancles lnclude oral halry leukoplakla ln paLlenLs wlLh Plv
lnfecLlon.
Lelomyomas and lelomyosarcomas ln lmmunocompromlsed chlldren,
nasopharyngeal carclnoma, and 8urklLL lymphoma are among oLher neoplasms
caused by L8v.



8) on ML1ICkMIN
uear yln llng,

you asked me yesLerday Lo vlva you on MeLformln and lLs usage ln varlous cllnlcal
scenarlos. l posL here a few common Cs on MeLformln.


1hls charL ls lmpL as lL shows Lhe relaLlonshlp beLween sLress causlng PlCP Clucose
whlch cannoL be cleared by low lnsulln!! and wlLh lncrease of shunLlng Lo lacLaLe
now made worse by poor clearance.


uear ?L,

We no longer use henformln. 8uL lL has un[usLlflably glven MeLformln a bad name.
MeLformln ls acLually a very safe drug when used mlndfully.

under whaL condlLlons does LacLlc acldosls occur? ?ou run maraLhons, lL ls lmpL LhaL
you undersLand Lhls. Can you descrlbe how you felL llke when lacLlc acldosls
occured?
uo you recall noL havlng much appeLlLe desplLe runnlng such a long dlsLance,
anorexla ls common. Were you nauseaLed, perhaps even vomlLlng? ?ou felL
dellrlously happy when you flnlshed buL Lhls alLered level of consclousness could be
due Lo meLabollc cause!!! ?es you had hyperpnoea, abdomlnal paln and LhlrsL. And l
recall you Lelllng me LhaL you were anurlc and had uA8k urlne! lease dun do lL
agaln!!!

8ed blood cells produce lacLlc acld as a byproducL of Lhe regeneraLlon of A1 durlng
anaeroblc glycolysls buL cannoL use lacLlc acld
1ake home LhaL when you have a paLlenL wlLh Llssue underperfuslon and hypoxla
colncldlng because of lllness or surgery, avold MeLformln!

LacLlc acldosls ls a broad-anlon gap meLabollc acldosls caused by lacLlc acld
overproducLlon or underuLlllzaLlon. 1he A8C and slmple maLhs wlll Lell you Lhls.

CverproducLlon of lacLlc acld occurs when Lhe body musL regeneraLe A1 wlLhouL
oxygen (Llssue hypoxla). ClrculaLory, and pulmonary dlsorders are commonly
responslble.

underuLlllzaLlon lnvolves removal of lacLlc acld by oxldaLlon or converslon Lo
glucose. L|ver d|sease, |nh|b|t|on of g|uconeogenes|s by metform|n!! are common
causes. oor rena| funct|on a|so makes excret|on poor.

ApproxlmaLely 1400 mmol of lacLlc acld are produced dally, whlch are buffered by
1400 mmol of PCC3 Lo form sodlum lacLaLe. 1he ||ver |s respons|b|e for ox|d|z|ng
|actate to restore th|s amount of nCC3. 1he role of Lhe llver ln lacLaLe homeosLasls
ls conslderable.

1he k|dneys contr|bute to |actate remova| |n three ways: excret|on,
g|uconeogenes|s, and ox|dat|on.
Ma||gnant ce||s produce more |actate than norma| ce||s, even under aeroblc
condlLlons. 1hls phenomenon ls enhanced lf Lhe Lumor ouLsLrlps Lhe blood supply!!


?ln llng,

ls noLe Lhe word S1A8LL! roblem sLarLs when 8enal funcLlon ls deLerloraLlng or ls
expecLed Lo deLerloraLe buL nC1 ln Lhe awareness of Lhe PC.

No one w||| use |t when eGIk |s |ess than 30 or you are wa|k|ng a th|n ||ne.

1ell me whaL common condlLlons can lead Lo a cllnlcal deLerloraLlon of renal
funcLlon?
N|nety percent of metform|n |s excreted unchanged by the k|dneys and lacLlc
acldosls Lyplcally occurs ln paLlenLs wlLh renal lnsufflclency. Lven mlld renal dlsease
lncreases Lhe rlsk of lacLlc acldosls.
rof: A metform|n dosage of 8S0mg tw|ce a day, or S00mg three t|mes a day,
usua||y g|ves good d|abet|c contro|. 1here |s not much po|nt g|v|ng beyond 2000mg
a day.

CauLlon ls needed when lncreaslng Lhe dally dosage beyond Lhls, especlally ln Lhe
elderly and Lhose wlLh mlld renal dlsease.

SlgnlflcanL morLallLy ( as hlgh as 30) ls assoclaLed wlLh blguanlde-lnduced lacLlc
acldosls and aLLenLlon should be focused on prevenLlon Lhrough awareness of Lhe
rlsk facLors.

PearL fallure and meLformln remalns a blL confuslng. l have seen papers whlch
propose LhaL lL ls noL anymore dangerous Lhan usual. Agaln Lhe word ls S1A8LL vs
unS1A8LL.

A paLlenL who comes ln wlLh fluld overload and low C2 saL ls dlfferenL from one who
ls comforLable aL home well malnLalned on medlclne and sLable.

Someone who comes ln wlLh mlld lllnesses llke a u81l ls obvlously dlfferenL from
anoLher wlLh severe pneumonla.

Someone comlng for exclslon of an ln grown Loenall ls dlfferenL from an elderly
woman golng for a LoLal hlp replacemenL.

WhaL wlll you do lf you are refered such dlabeLlc paLlenLs as above?

?L: lor Lhe shorL Lerm sLay ln hosplLal for unsLable paLlenLs, slldlng scale wlll be a
good cholce. unLll we know paLlenL ls more sLable and Laklng orally well, we wlll
keep Lhem on elLher slldlng scale or regular lnsulln flrsL

8Cl: Can you pls elaboraLe on Lhe Slldlng Scale used here?

?L: We glve pL subcuL shorL acLlng lnsulln ln[ecLlon based on Lhelr blood glucose
level every 4 hourly. 1he ranges can be 2 unlLs of lnsulln lf glucose ls 3 Lo 10, 4 unlLs
for 10 Lo 13 and so on. Slldlng scale can be augmenLed lf glucose ls hard Lo conLrol.

LacLlc acldosls ls an uncommon buL poLenLlally faLal adverse effecL. 1he reporLed
frequency of lacLlc acldosls ls 0.06 per 1000 paLlenL-years, mosLly ln paLlenLs wlLh
predlsposlng facLors.

Lxamples of meLformln-lnduced lacLlc acldosls scenarlos lnclude:

A 69-year-old man, wlLh renal lmpalrmenL and cardlac fallure, was prescrlbed
meLformln due Lo falllng glycaemlc conLrol on gllbenclamlde monoLherapy. Pe was
well for slx weeks, Lhen developed lacLlc acldosls and dled wlLhln 3 days.
1ell me whaL should have been done lf we can Lurn back Lhe clock?

An elderly man had a LoLal hlp replacemenL. osL-surglcal lacLlc acldosls caused Lhe
deaLh of Lhls 70-year-old man whose meLformln was noL wlLhdrawn aL Lhe Llme of
surgery.
lf you are Lhe resldenL, whaL would you have done lnsLead?

A 36-year-old woman, wlLh no predlsposlng dlsease, dled from lacLlc acldosls
followlng ma[or abdomlnal surgery for Ca Colon. MeLformln was wlLhdrawn only for
Lhe day of surgery.
WhaL should you have done lnsLead lf asked Lo see Lhls paLlenL?
1he r|sk factors for metform|n-assoc|ated |act|c ac|dos|s |nc|ude seps|s, h|gh
dosage, |ncreas|ng age, and DLnDkA1ICN. 1he |ast |s often forgotten! In
s|tuat|ons pred|spos|ng to dehydrat|on such as IAS1ING for surgery, or contrast
rad|ography, metform|n shou|d be ceased at |east 48 hours pr|or to the procedure
(or on adm|ss|on for an emergency procedure). It |s not restarted unt|| the pat|ent
has fu||y recovered and |s eat|ng and dr|nk|ng norma||y. 1he g|ucose |eve|s of
pat|ents |n CA1A8CLIC states, e.g. seps|s or |n the post-operat|ve per|od, shou|d be
mon|tored and Short-term |nsu||n therapy |s strong|y adv|sed for Mx.
1ry not to use above 70 years o|d, and |f us|ng be very carefu| w|th rena| funct|on.
remember that by the t|me b|ochem|stry |s abnorma|, the rena| funct|on |s a|ready
s|gn|f|cant|y affected bec of rena| reserve
?L: lor Lhe flrsL scenarlo, hls renal lmpalrmenL already sLop us fr uslng meLformln.
alrlng up wlLh a hearL fallure causlng lncrease Llssue hypoxla, lacLlc acldosls ls llkely.
Cllbenclamlde ls such a long acLlng Su, hypo eplsodes ls rlsky. And gllbenclamlde
whlch shouldnL be use ln renal lmpalrmenL. We can use gllclazlde.. a newer gen Su,
lesser hypo eplsodes, lssser welghL galn and can be used ln mlld renal lmpalrmenL
wlLh cauLlon. Pe wlll also be a good candldaLe Lo sLarL lnsulln. When he ls belng
admlLLed for hearL fallure, Lemporary use of slldlng scale ls warranLed lf hes
unsLable.
8Cl: AS a ru|e, p|s do NC1 use g||benc|am|de |n the e|der|y. Its |ong act|ng and
even |ts metabo||tes are AC1IVL. G||caz|de |s excreted by the ||ver so |ts re|at|ve|y
safer even |n rena| |mpa|rment.
uesplLe Lhe presence of many unlque classes of drugs Lo LreaL hyperglycemla ln
paLlenLs wlLh Lype 2 dlabeLes, meLformln remalns Lhe urug of Cholce.
MeLformln caused less welghL galn compared wlLh elLher Lhe Lhlazolldlnedlones or
sulfonylureas. Metform|n decreased |ow-dens|ty ||poprote|n |eve|s compared wlLh
plogllLazone, sulfonylureas, and u-4 lnhlblLors.

aLlenLs Laklng sulfonylureas had a fourfold hlgher rlsk of mlld or moderaLe
hypoglycemla compared wlLh meLformln alone. 1hls ls a Lremendous advanLage of
Lhe drug.

MosL lmporLanLly as far as evldenced based medlclne ls concerned, MeLformln ls
unlque ln belng noL only as effecLlve as any oLher oral anLldlabeLlc Lherapy ln
conLrolllng blood glucose, but a|so hav|ng an unpara||e|ed c||n|ca| database re|at|ng
to |mproved c||n|ca| outcomes |n pre-d|abet|c sub[ects, and pat|ents w|th
estab||shed type 2 d|abetes.


9) on DIA8L1LS!
y|n ||ng has asked that I cont|nue w|th her V|va voce throughout the CN per|od.

Wh||e |t |s very |mportant that we keep the A1c |eve| as c|ose to norma| as we
safe|y can, th|s MUS1 vary accord|ng to the pat|ent's c||n|ca| c|rcumstances, age,
r|sk for hypog|ycem|a, soc|a| background and many other factors.

Wh|ch pat|ents w||| you be happy to have A1c |eve|s at 10, wh|ch, for
comp||cated reasons, you can't get them |ower or do not want |t |ower?

And who w||| you want at target of < 7 and even |n some < 6.S?

Ior a pat|ent who |s symptomat|c and has a b|ood sugar |eve| of >11.1mmo|]| he
c|ear|y has d|abetes. nowever can you d|agnose w|th

- Measurement of the hemog|ob|n A1c |eve|,
- Measurement of the fast|ng g|ucose |eve|,
and what are |ts ||m|tat|ons?

Whlch ls MC8L 8ellable, MC11 or Lhe hemoglobln A1c level?

lease noLe LhaL blood glucose levels llke any laboraLory assay can vary even ln
perfecLly normal people.
We do one LesL Lo see wheLher a person has dlabeLes, and Lhen unless Lhe values
are clearly abnormal, we need Lo repeaL Lhe same LesL Lo verlfy wheLher LhaL value
ls Lrue. 8ecause lab errors can occur, lLs lmpL Lo repeaL Lhe same LesL.

1he LreaLmenL of uM ls more Lhan conLrolllng blood sugars, ln any real llfe and exam
slLuaLlon, a global evaluaLlon ls essenLlal. 8lood pressure: whaL ls Lhe presenL
LargeLs?

Lvery pat|ent who has d|abetes and who |s o|der than age 40 years |s somebody
who w||| need to be on stat|n therapy! 1he occaslonal man who swears LhaL Lhe
sLaLln had caused Lu ls also a dlfflculL slLuaLlon as l am noL sure lLs Lhe uM or Lhe
drug. WhaL ls Lhe role of fenoflbraLe lf any?

1he role of ACLl and A88s ls anoLher common exam C. Wlll you use angloLensln-
converLlng enzyme lnhlblLors or angloLensln recepLor blockers for Lhe prevenLlon of
nephropaLhy ln paLlenLs who do noL have elevaLed blood pressure levels?
Pow wlll you advlse your paLlenL regardlng alcohol lnLake?
?L : we should lndlvlduallsed our PbA1c LargeL accordlng Lo a paLlenL's age,
comorbldlLls and general condlLlon. Ior a young pat|ent say 40-S0 years o|d hav|ng
12DM, we wou|d ||ke h|s nbA1c to be t|ght|y contro|, target|ng a 6.S-7 to de|ay
the onset of m|crovascu|ar and macrovascu|ar d|sease.
Powever lf we are looklng aL an e|der|y, fra||, 70 year o|d d|abet|c pat|ent, we
wou|d be happy |f h|s nbA1c |s around 8-10, LlghLenlng Lhe glucose conLrol equals
expecLlng more hypoglycemlc evenLs whlch ls deLrlmenLal Lo Lhe old.
uM can be dlagnosed when a paLlenL has a PbA1c of >6.3. PbA1c of 6-6.3 ls
consldered re ulabeLes. we can also dlagnose uM by fasLlng blood glucose of >7.0
lf Lhere ls sympLoms. 2 readlngs ls needed lf Lhere ls no sympLoms. IIG |s when I8G
rang|ng S.6-7 and IG1 when 2 hours post CG11 8G 7.8-11.0

8e careful when uslng PbA1c Lo dlagnose ln paLlenLs who have h|gh k8C turnover
eg tha|asem|a, any hem|g|ob|nopath|es, rena| d|sease and eLc.
l would llke Lo Lhlnk LhaL PbA1c ls more rellable as lL measures glucose conLrol for
over a longer perlod of Llme.



8 LargeL ls aL 130/80 for paLlenLs wlLh uM, we no longer use Lhe 123/73 LargeL
anymore. Lhere ls no beneflL ln lowerlng 8 Lo such level ln Lhls group of paLlenLs.

Anyone above 40 who has uM deserves a sLaLln. afLer sLarLlng sLaLlns and
conLrolllng Lhe blood sugar, lf 1C ls sLlll hlgh, fenoflbraLe ls warranLed. lenoflbraLe
can also be used ln paLlenLs who cannoL LoleraLe sLaLlns eg from Lhe myopaLhy.

ACL-l and A88 ls beneflclal for uM paLlenL and we are LaughL Lo use Lhem as flrsL
llne ln all uM paLlenL due Lo Lhe renal proLecLlve effecL. ACL can help prevenL
nephropaLhy and reduce proLelnurla. Lhese paLlenLs commonly have deranged renal
funcLlon from dlabeLes, lL ls noL enLlrely conLralndlcaLed Lo use ACL/A88 as long as
renal proflle are monlLored, sLop lf Lhere ls >30 ralsed of creaLlnlne durlng a repeaL
renal proflle ln more Lhan 2 weeks. we would noL use ACL - l once creaLlnlne ls >200.

We are commonly LaughL Lo use ACL-l as flrsL llne and lf paLlenL cannoL LoleraLe ACLl
mosLly due Lo an ACL lnduced cough we would use an A88 lnsLead.
Alcohol : cuL off unlLs for men ls 21 and women 14 per week. buL of course Laklng
many unlLs ln one seLLlng ls bad. encourage moderaLe alcohol lnLake.
uear yln llng
Pba1c ls beLLer Lhan MCC1. A1C capLures chronlc hyperglycemla beLLer Lhan Lwo
assessmenLs of fasLlng or 2-h oral glucose Lolerance LesL of plasma glucose

ulabeLes has been dlagnosed for decades wlLh fasLlng plasma glucose or, wlLh an
oral glucose Lolerance LesL (CC11). Pyperglycemla as Lhe blochemlcal hallmark of
dlabeLes ls unquesLlonable. Powever, fasLlng and 2-h MC11 gauge [usL a momenL of
a slngle day. Many2 facLors affecL Lhls sample whlch Pba1c overcomes.

8u1 Pba1c LesLlng lacks sLandardlzaLlon and dlfferenL labs provlde dlfferenL values
for even a same sample. 1h|s on top of haemo|yt|c anaem|a or |ack of LC or bone
marrow prob|ems. So we need Lo lnLerpreLe mlndful of Lhese.

When there |s InD, hypog|ycaem|a |s DANGLkCUS. |t can ppt arrthym|as and even
ACS. nence |n proven DM CnD, the target shd NC1 be |ower than 7.

Serum frucLosamlne was someLhlng l used Lo LesL buL lLs unrellable. ln Lhalassaemla
LralL paLlenLs bld sugar proflles remaln our bedrock. Same for renal fallure paLlenLs.

1op secreLs:

Ibs, nba1c and 2n va|ues are a|| corre|ated to ret|nopathy the most spec|f|c
comp||cat|on of dm

Ibs |s poor|y corre|ated to CnD
8U1 2hpp and nba1c |s we|| assoc|ated.

8ld sugars sLarL dropplng ln value by 3 every hour afLer venesecLlon
So lf Lhe speclmen slLs on a bench whlle Lhe Lechnlclan resLs, you are noL golng Lo
geL anyLhlng close Lo reallLy. Worse ln PC1 WLA1PL8.

Pba1c ls noL affecLed ln Lhls way.



uear ?L,

Ak8 vs ACLI

ln chooslng beLween ACLl and A88 Lherapy for paLlenLs wlLh Lype 2 dlabeLes
dlabeLlc nephropaLhy, you have Lo conslder ev|dence of proven rena| protect|ve
benef|t for Ak8 treatment versus ev|dence of a morta||ty benef|t for ACLI
treatment shown |n pat|ents w|thout estab||shed d|abet|c nephropathy.

Ak8 appears super|or to de|ay|ng progress|on to rena| fa||ure.
8ut IN NCN kC1LINUkIC A1ILN1S, ACLI has better resu|ts w|th regards to
morta||ty.

ACLI |n genera| n1 pat|ents has better outcome for CnD.

1here ls no rouLlne role for comblnlng boLh
ou reca|| Cn1arget tr|a|. It was a huge tr|a| test|ng 1e|m|sartan vs kam|pr|| and |ts
comb|nat|on. 1he ang|otens|n receptor b|ocker te|m|sartan was "non|nfer|or" to
the ACL |nh|b|tor ram|pr|| |n pat|ents w|th vascu|ar d|sease or h|gh-r|sk d|abetes |n
th|s |andmark tr|a|

Powever, Lhe comblnaLlon of Lhe Lwo drugs was assoclaLed wlLh more adverse
evenLs wlLhouL an lncrease ln beneflL.



10) on Dyspnoea
Dear L,

A S6 years o|d |ady was brought by her daughter to see you. She has many years of
breath|essness and wheez|ng.
She used to smoke when she was young. She |s now hypertens|ve and d|abet|c for
10 years. She has been cough|ng bad|y w|th puru|ent sputum the |ast 2 weeks. She
wakes up at Sam cough|ng and breath|ess.

She |s on g||caz|de and metform|n. She Is on an ACLI for n1.
SnL USL A LADA LUS Stero|d INnALLk And takes theophy|||ne tab|ets.
ner dr gave her a macro|yte ant|b|ot|c for ' bronch|t|s' .
What w||| you do now?
|n L|ng: 1hanks rof. 1hls lady ls havlng an exacerbaLlon of her obsLrucLlve alrway
dlsease evldenL from Lhe lncrease breaLhlessness/purulenL spuLum and cough.

WhaL sLrlkes me flrsL ls Lhe macrollde anLlbloLlc belng glven Lo her when she's Laklng
Lheophylllne. l wonder whlch macrollde ls lL. dld she brlng lL wlLh her? We wouldnL
wanL Lo glve her any eryLhromycln/cllndamycln for Lhe fear of Lheophylllne LoxlclLy
whlch wlll cause arrhyLhmla and selzure. AzlLhromycln ls sald Lo lnLeracL less wlLh
Lheophylllne and we commonly see Lhls comblnaLlon ln CP.

8eLake a Lhorough hlsLory Lo dlagnose asLhma, CCu and rule ouL slnlsLer problems.
ensure no sx showlng Lheophylllne LoxlclLy- Cl problems, palplLaLlons. assess her
recenL conLrol of her dlsease. ls Lhe LA8A and lnhaled sLerold enough?

Lxamlne her properly. ls Lhere any clubblng, cyanosls, her oxygen saLuraLlons, Lhe
lungs. Any slgns of pneumonla on examlnaLlon, creplLaLlons, wheezlng. any slgns of
hearL fallure. does she needs Lo be admlLLed.

A Cx8 ls warranLed. C8C and u&L would be helpful. LCC as well.

1ake off her meLformln for Lhe Llme belng and sLarL her on a shorL acLlng 82 agonlsL,
a comblnaLlon of 82 agonlsL and anLlchollnerglcs would be besL lf l dlagnosed her as
havlng CCu. She can Lake lL every 6 hourly for Lhe Llme belng.

She ls on a LA8A and lnhaled sLerolds. l assumed she was belng LreaLed as asLhma by
her docLor, based on her dlagnosls and conLrol, Lhls prevenLer reglme can be
augmenLed wlLh a LAAC lf her she ls havlng CCu lnsLead of asLhma. A small dose of
Lheophylllne wlll be helpful Loo.

A shorL course of oral sLerolds wlll be helpful. AbouL 3 days.

As for anLlbloLlcs a resplraLory qulnolone would be beLLer. noL clprofloxacln. l would
use augmenLln buL why rlsk Lhe Cl slde effecLs.

l wlll ask her Lo come back ln 3-3 days or earller ls she's dolng worse.

uear ?ln llng,

8e sure lLs noL chronlc hearL fallure Llpped CvL8 wlLh a L81l. She's uM and P1 so
rlsk ls hlgh. ls noLe she ls nC1 on a sLaLln, does lL maLLer whaL her value ls?
She may noL have chesL paln bec of uM and yeL have crlLlcal chd. A basellne LCC ls
needed and furLher lnvesLlgaLlons for CPu may be needed..

orLable C2 saL measuremenL ls avallable aL abL 8m400. lL shd be measured lf
avallable. Ask her Lo blow ouL a maLch aL 1 feeL.

Cld people may nC1 have fever so LhaL ls nC1 A CCCu lndlcaLor of sepsls. ASk lC8
8LMC88lu S1A1L l8CM 1PL uAuCP1L8!

It |s often forgotten that smok|ng |nduces cytochrome 4S0 (C) 1A2, resu|t|ng |n
a|tered concentrat|ons and requ|red doses of drugs metabo||zed by th|s route. ls
name me some common drugs meLabollzed by Lhls.

Converse|y, upon cessat|on of smok|ng, concentrat|ons of these drugs can r|se to
tox|c |eve|s un|ess appropr|ate dose ad[ustments are made.

uocLors ln lnLernal Medlclne need Lo be aware of Lhls, lf poLenLlal laLrogenlc harm Lo
paLlenLs ls Lo be avolded.

1he Inducers of 4S0
Carbemazep|nes
k|famp|c|n
A|coho| (chron|c)
henyto|n
Gr|seofu|v|n
henobarb|tone
Su|phony|ureas
1heophy|||ne |s metabo||sed by cyp 2a1.
Smok|ng |nduces cyp 2a1 wh||e drugs ||ke c|met|d|ne, c|prof|oxac|n, erythromyc|n
and c|ar|thromyc|n |nh|b|ts |t and cause |ncrease r|sk of tox|c|ty
1he cyLochrome 430 enzymes are found prlmarlly ln Lhe llver, alLhough some (eg,
C?3A4) are also found ln subsLanLlal amounLs ln Lhe lnLesLlne. 1hey are lnvolved ln
Lhe meLabollsm of mosL medlcaLlons and are Lhe mechanlsm by whlch mosL
pharmacoklneLlc drug lnLeracLlons occur. Cytochrome 4S0 3A4 (C3A4) |s the
superstar, lL geLs aLLenLlon because a ma[orlLy of drugs are meLabollzed by C?3A4.

11) on GkAVLS IN kLGNANC
uear yln llng
Pappy Cn? Lo my 'llver' daughLer.
A young lady of 23 has Craves ulsease. She ls newly marrled and noL on
conLracepLlon. resenLly she ls on carblmazole 10mg dally and ls euLhyrold. She has
been on LreaLmenL for Lhe lasL 1 year. She has mlld propLosls and a moderaLe slze
golLre.

AL follow up you aLLend Lo her. WhaL wlll you do for her?
When hyperLhyroldlsm ls noL conLrolled ln pregnancy, compllcaLlons lnclude
mlscarrlage, pregnancy-lnduced hyperLenslon, premaLure blrLh, low blrLh welghL,
lnLrauLerlne growLh resLrlcLlon, sLlllblrLh, Lhyrold sLorm, and maLernal congesLlve
hearL fallure. 1herefore, proper dlagnosls and LreaLmenL ofCraves' dlsease and
hyperLhyroldlsm durlng pregnancy ls essenLlal. ?our answer MuS1 sLarL wlLh pre
pregnancy LreaLmenL of women who have Craves' dlsease, they shou|d conce|ve
on|y after they are euthyro|d. ls sLrongly recommend conLracepLlon unLll Lhls ls
achleved, and recommend LhaL physlclans offer counsellng Lo women regardlng Lhe
lmpllcaLlons of LreaLmenL on concepLlon plans.

1kAb |eve|s tend to r|se after kad|od|ne and rema|n e|evated. Ior th|s reason Mx
on pregnancy post kAI |s more mahfan and |n Ms|a we do not usua||y use th|s |n
young women. Cur follow up LreaLmenL ls noL so greaL and paLlenLs ofLen defaulL. lf
8Al ls performed, a pregnancy LesL should be done 48 hours prlor Lo Lhe 8Al
admlnlsLraLlon. When she says nC1 8LCnAn1, beLLer 1LS1!
lor anLlLhyrold drugs, women should be lnformed abouL Lhe rlsks assoclaLed wlLh
propylLhlouracll (1u) and Carblmazole, and lf Lhese drugs are used, 1U shou|d be
used |n the f|rst tr|mester of pregnancy. Carblmazole poses rlsks Lo Lhe feLus lf used
ln Lhe flrsL LrlmesLer as you noLed.
k|v d|scont|nuat|on of 1U after the f|rst tr|mester and sw|tch|ng to carb|mazo|e,
to decrease the r|sk of ||ver d|sease assoc|ated w|th 1U.

Pence, 1he prlmary LreaLmenL for hyperLhyroldlsm durlng pregnancy ls anLlLhyrold
drugs. 8ecause anLlLhyrold drugs cross Lhe placenLa, care needs Lo be Laken wlLh Lhe
use of anLlLhyrold drugs durlng pregnancy. ln parLlcular, Lhe maln concern ls Lhe
ablllLy of carblmazole Lo cause congenlLal malformaLlons - Lhese compllcaLlons are
noL assoclaLed wlLh Lhe use of 1u.

1u, however, carrles a rlsk of llver LoxlclLy, and hence leL 1u be used ln Lhe flrsL
LrlmesLer, and LhaL paLlenLs swlLch Lo carblmazole ln second semesLer.
1u crosses Lhe placenLa and breasL mllk less.

8eLa blockers are noL Lyplcally recommended durlng pregnancy, as Lhey are
assoclaLed wlLh lnLrauLerlne growLh resLrlcLlon, low feLal hearL raLe, and
hypoglycemla ln newborns.

All woman Laklng anLlLhyrold drugs durlng pregnancy MuS1 undergo regular
monlLorlng of lree 14 and 1SP, so LhaL Lhe Iree 14 va|ues rema|n at, or [ust above
the upper ||m|t of norma|, wh||e tak|ng the |owest poss|b|e dose of ant|thyro|d
drugs. Iree 14 and 1Sn shou|d be measured every two to four weeks at the start of
treatment, and every four to s|x weeks after, to ach|eve the target b|ood |eve|s.
LS remember the ||m|tat|ons of 1Sn tests on pregnancy.

1yp|ca||y, because hyperthyro|d|sm often norma||zes dur|ng pregnancy bec of
h|gher requ|rements and vo|ume of d||ut|on, ant|thyro|d drugs can be d|scont|nued
|n the th|rd tr|mester |n as many as 20 to 30 of pat|ents.

Ior women who have h|gh 1Sn receptor ant|body (1kAb) |eve|s, they may need to
cont|nue w|th ant|thyro|d drug treatment unt|| de||very bec these Abs may cause
feta| hyperthyro|d|sm as you po|nted out.

1hyroldecLomy for Craves' ulsease uurlng regnancy
If a woman |s a||erg|c to ant|thyro|d drugs, requ|res h|gh doses to contro|
hyperthyro|d|sm, or |s not fo||ow|ng her drug therapy, thyro|dectomy -- |s needed,
the opt|ma| t|me |s dur|ng the second tr|mester of pregnancy.At the t|me of
surgery, the 1kAb |eve|s shou|d be measured to assess the potent|a| r|sk of
hyperthyro|d|sm |n the fetus.

1here are a number of rlsks Lo Lhe feLus lncludlng:
feLal hyperLhyroldlsm
neonaLal hyperLhyroldlsm
feLal hypoLhyroldlsm
neonaLal hypoLhyroldlsm

1he facLors LhaL can affecL feLal rlsk lnclude: poor contro| of hyperthyro|d|sm
throughout pregnancy, wh|ch can cause trans|ent centra| hypothyro|d|sm |n the
fetus, h|gh doses of ant|thyro|d drugs, wh|ch can cause feta| and neonata|
hypothyro|d|sm, h|gh |eve|s of serum 1kAb wh|ch can cause feta| or neonata|
hyperthyro|d|sm.
leLal and neonaLal hyperLhyroldlsm occurs ln beLween 1 and 3 of all pregnanL
women wlLh an acLlve or a pasL hlsLory of Craves' hyperLhyroldlsm.

In a pregnant woman who has an act|ve or past h|story of Graves' d|sease, 1kAb
shou|d be measured by 20 to 24 weeks of gestat|on. A va|ue that |s more than
three t|mes the upper ||m|t of norma| |s cons|dered a marker of r|sk to the fetus.
keypolnLs:
aLlenLs who are recelvlng LreaLmenL should recelve pre-concepLual advlce wlLh a
vlew Lo opLlmal preparaLlon prlor Lo pregnancy. 1hls lncludes ensurlng Lhey are
euLhyrold prlor Lo concepLlon and alLerlng medlcaLlon Lo 1u whlch ls felL Lo be
superlor Lo carblmazole durlng pregnancy, especlally ln Lhe flrsL LrlmesLer due Lo
reduced lncldenL of aplasla cuLls.

CurrenL evldence suggesLs LhaL followlng organogenesls, carblmazole or
meLhlmazole should be re-lnLroduced due Lo a posslble lncreased rlsk of hepaLlLls
wlLh 1u.

1hose on a block and replace reglme should also be swapped Lo 1u alone as
Lhlonamldes wlll cross Lhe placenLa buL levoLhyroxlne wlll noL, Lhus lncreaslng Lhe
rlsk of foeLal golLre and hypoLhyroldlsm.

regnanL paLlenLs on LreaLmenL should have frequenL 1l1's LhroughouL pregnancy
(monLhly) and Lhe dose reduced Lo Lhe lowesL posslble Lo malnLaln euLhyroldlsm
wlLh 14 aL Lhe upper llmlL of Lhe reference range.
uoses are reduced ln Lhe laLLer sLages of pregnancy, and noL lnfrequenLly sLopped
alLogeLher as Lhe condlLlon undergoes remlsslon. lf hyperLhyroldlsm ls secondary Lo
Crave's ulsease (or paLlenL has had prevlous deflnlLlve LreaLmenL such as surgery or
8Al) Lhen 1SP recepLor anLlbodles should be measured as hlgh LlLres can lndlcaLe
lnLrauLerlne or neonaLal LhyroLoxlcosls.


WlLh ur uonald Alexander, 8eader ln Medlclne, unlverslLy of Clasgow. 1hls ls Lhe
ClanL who dld much research on Lhe radlo assays of Lhe 1hyrold and who advocaLed
Lhe 8lock and 8eplace meLhod of LreaLmenL. Pe Look me under hls wlngs as a osL
CraduaLe lellow ln lnLernal Medlclne.

12) on 8ASICS
uear ?ln Chok,
& 1o lan my nephew readlng Medlclne ln Canberra,

lf l were Leachlng you lan, l would had been vL8? Pard on you. l would have ZL8C
1olerance for errors and omlsslons. l would have been doubly demandlng of you
compared Lo oLher sLudenLs bec you are my nephew.

l have been hard on yln llng Loo for my wlfe and l LreaL her llke a daughLer. As for my
oLher sLudenLs, Modern proprleLy demands LhaL l Lone down 3 gears.

A generaLlon ago when Mslan candldaLes saL for Lhe M8C exams ln uk, we were
noL afrald of Lhe cllnlcal cases as we were well exposed Lo many cllnlcal problems ln
our dally work. 8uL LheoreLlcal quesLlonlng can be a problem as we may noL be
famlllar wlLh Lhe lASPlCn of quesLlons ln voque.

A good frlend was asked. 'WhaL ls Lhe chemlcal LesL used Lo deLermlne Lhe Pb level?'
for hls vlva. ?r1 blochem. uld Lhe LesL ourselves buL Cood heavens whaL's Lhe name
of Lhe damn chemlcal? Pe falled.

l dld Lhls experlmenL ln year1 blochem and ln yr4 obs posLlng we Lhe mlnlon med
sLudenL had Lo check Lhe paLlenLs Pb before Lhey can be dlscharged. So lL's lasered
lnLo our bralnsLems.

1he paLlenL's blood ls mlxed wlLh urabkln's soluLlon, a soluLlon LhaL conLalns
ferrlcyanlde and cyanlde. (8lsked my llfe sLudylng medlclne!) 1he ferrlcyanlde
oxldlzes Lhe lron ln Lhe hemoglobln, Lhereby changlng hemoglobln Lo
meLhemoglobln. MeLhemoglobln Lhen unlLes wlLh Lhe cyanlde Lo form
cyanmeLhemoglobln. CyanmeLhemoglobln produces a color whlch ls measured ln a
specLrophoLomeLer. 1he color relaLes Lo Lhe concenLraLlon of hemoglobln ln Lhe
blood whlch we obLaln by comparlng wlLh a sLandard charL.

1oday l am golng Lo ask you a serles of baslc quesLlons.

1. our pat|ent has LSk 11S. What are your thoughts?
?L: 1here's only a few causes for Lhree dlglLs esr. MulLlple myeloma, CCA(Lemporal
arLerlLls), advanced mallgnancy, 18 and SLL (connecLlve Llssue dlsease) and also ln
severe sepsls.
rof : And we musL noL lC8CL1 causes of a LCW LS8 Loo!

Lower-Lhan-normal levels can occur wlLh:

Congest|ve heart fa||ure
nyperv|scos|ty
nypof|br|nogenem|a
Low p|asma prote|n (due to ||ver or k|dney d|sease)
o|ycythem|a
S|ck|e ce|| anem|a
1he raLe of fall of red cells ln anLl-coagulaLed plasma ls lnfluenced by a number of
facLors. SedlmenLaLlon ls lnfluenced greaLly by Lhe exLenL Lo whlch Lhe red cells form
rouleaux or large clumps of cells. 1hls rouleaux formaLlon ls relaLed Lo Lhe plasma
proLelns whlch overcome Lhe negaLlve surface charge on red cells.

1he haemaLocrlL also lnfluences Lhe LS8. Anaem|a acce|erates sed|mentat|on and
po|ycythaem|a retards |t.

Are you all aware LhaL Aglng alone elevaLes lL? erhaps some low grade
lnflammaLlon kllls us all evenLually. upper llmlL of normal for males ls Age dlvlde by
2 and for lemales ls Age LuS 10 dlvlde by 2!

Are you aware LhaL merely belng ulabeLlc also lncreases lL? Maybe Lhe same reasons
cause LhaL.
WlLh lncreaslng age afLer 30 years, Lhe LS8 rlses and, ln Lhe elderly, many apparenLly
normal sub[ecLs have lncreased readlngs. 8uL lL ls nC1 3 flgure values.

hyslologlcal lncreases ln Lhe LS8 occur ln pregnancy and Lhe puerperlum.
1he LS8 ls a measure of Lhe presence and severlLy of lnflammaLory, auLo lmmune
and oLher morbld processes.

nC1L 1PA1 a normal LS8 cannoL be Laken Lo exclude dlsease

MosL acuLe or chronlc lnfecLlons, neoplasLlc dlseases, collagen dlseases, renal or
oLher dlseases assoclaLed wlLh changes ln plasma proLelns lead Lo acceleraLlon of
sedlmenLaLlon. lL ls also useful ln monlLorlng dlsease acLlvlLy ln cerLaln dlsorders. lL
has been used for Lhls purpose ln Luberculosls, rheumaLlc fever, rheumaLold
arLhrlLls, Podgkln's dlsease and non-Podgkln's lymphomas, myeloma and
macroglobullnaemla.

1he lnvesLlgaLlon of a very hlgh LS8 lnvolves full cllnlcal assessmenL of Lhe paLlenL
whlch wlll usually reveal Lhe cause. 1here are a number of well known assoclaLlons
wlLh a hlgh LS8 whlch lnclude whaL had been sLaLed and Lhe followlng:

kecent resp|ratory tract |nfect|on and anaem|a due to mycop|asma |nfect|on
Card|ac bacter|a| endocard|t|s |s |mpt as |t may be |ow grade and m|ssed. 8e
carefu| |n drug add|cts.
Mu|t|p|e mye|oma |s 1nL CLASSIC cause never to be m|ssed when gr|||ed. Cr come
back next year.
2. 1he LI1 came back. As nC you rev|ew the resu|ts. AS1 more than AL1 by 3 t|mes.
1houghts and why?

AL1 more than AS1 2 t|mes. 1houghts and why?

AS1 equa| to AL1. 1houghts?
?L: AS1 ls malnly ln Lhe mlLochondrla whlle AL1 ls cyLosollc. lnflammaLlon Lo
hepaLocyLes LhaL break down cell membrane wlll release much more AL1 compare
Lo AS1. Lg hepaLlLls, drug lnduced lnflammaLlon. Clrrhosls wlll cause hepaLocyLes
deaLh whlch release more AS1 llkewlse wlLh Ml.

AS1 2 Llmes more Lhan AL1 ls speclflc for alcohollc llver dlsease as alcohol lnduces
AS1.

AS1 and AL1 equlvalenL can mean llver cell deaLh or can be seen ln v chronlc llver
dlsease when Lhere ls noL much lncrease ln boLh Lransamlnases.


3. our pat|ents Urea |s e|evated but Creat|n|ne |s norma|. 1houghts and why? ?

4. Se ca|c|um |s tested be|ow norma|. at|ent Is we|| w|th norma| LCG. What are
your thoughts?
S. Se A|k phos h|gh and se ca|c|um h|gh

6. Se A|k phos norma| and Se ca|c|um h|gh

7. Se ca|c|um norma| and se A|k phos h|gh
uear yln llng,

Lhere are some unlque aspecLs of elevaLed ALkALlnL PCSPA1ASL

8ody sources of alkallne phosphaLase lnclude neo-osLeogenesls of bone, (nLW
8CnL lC8MA1lCn lS nLLuLu) lnLesLlnes, llver, placenLa, and whlLe blood cells.

CfLen elevaLed levels are assoclaLed wlLh compllcaLlons of Lhe llver or gallbladder.
Gamma g|utamy| transferase (GG1) w||| determ|ne hepat|c versus other or|g|ns of
a|ka||ne phosphatase e|evat|on.

ln Lhe presence of llver dlsease, lncreased levels of Camma gluLamyl Lransferase ls
seen buL ln persons who have recenLly lngesLed even mlnuLe amounLs of alcohol lL ls
elevaLed and ls Lherefore a less speclflc LesL. Isoenzyme test|ng ls also an opLlon Lo
deLermlne Lhe source of alkallne phosphaLase elevaLlon.

An elevaLlon of hepaLlc alkallne phosphaLase usually lmplles blllary LracL paLhology
wlLh resulLanL cholesLasls, buL Lhls elevaLlon also occurs wlLh |nf||trat|ve d|seases of
the ||ver, masses or abscesses of the ||ver,pr|mary b|||ary c|rrhos|s and pr|mary
sc|eros|ng cho|ang|t|s.

Where alkallne phosphaLase elevaLlon ls secondary Lo bone dlsease, lLs elevaLlon ls a
marker of osteob|ast|c act|v|ty. ln bony dlsease, Lhe alkallne phosphaLase elevaLlon
ls usually assoclaLed wlLh hypercalcemla. Common bone dlseases lnclude meLasLaLlc
bony leslons, ageLs dlsease, secondary hyperparaLhyroldlsm of renal dlsease,
osLeomalacla, rlckeLs, prlmary hyperparaLhyroldlsm, and even hyperLhyroldlsm. l
had paLlenLs wlLh Craves who presenLed wlLh hlgh Alk phos whlch normallsed on
LreaLmenL.

8u1 Lhe excepLlon ls mu|t|p|e mye|oma where hyperca|cem|a |s secondary to
osteoc|ast|c bone d|sease and the a|ka||ne phosphatase |eve| |s norma|. I found th|s
fasc|nat|ng as a student.

Cllnlcally, patho|og|c fractures of the sternum are cons|dered pathognomon|c of
mu|t|p|e mye|oma, and bone pa|n of the r|bs or back that |s exacerbated by
movement |s cons|dered character|st|c. Add ralsed se calclum, hlgh esr, normal alk
phos and ralsed globullns and l wlll knock your head lf you cannoL dlagnose.

Dur|ng pregnancy, materna| a|ka||ne phosphatase |ncreases. 1h|s |s the resu|t of
p|acenta| a|ka||ne phosphatase product|on, and the e|evat|on reso|ves
puerper|um.
uear ?ln llng,

l had only seen 1 paLlenL wlLh very hlgh ulrecL 8lllrubln and normal Alk phos.
1hls ls ln a paLlenL wlLh a leaklng 1 Lube. ulrecL con[ugaLed blllrubln leaked lnLo Lhe
perlLoneum and was absorbed back lnLo Lhe clrculaLlon


8. at|ent |s c||n|ca||y suspected to have ma|ar|a. Consu|tant asked for 8IM k 3
1he nC dut|fu||y on 3 days took 3 samp|es and a|| 3 were negat|ve. What cou|d be
wrong?
uear ?ln llng,

1aklng blood fllms for malarla paraslLes shd be done when paraslLaemla ls hlghesL.
1hls ls when fever ls rlslng. So lL ls noL Lhe PC merely Laklng blood from a veln when
lL ls convenlenL Lo hlm.

up Lo 3 speclmens can be Laken ln Lhe same day lf fever ls noLed Lo be rlslng. Pence
for slmpllclLy Lhls ls done vla a flnger prlck.

A Lhlck fllm for screenlng and a Lhln fllm for ldenLlflcaLlon ls made each Llme. PCs
musL know Lhese Lechnlques as malarla screenlng ls common ln Msla.

|s make sure that the a|coho| used to c|ean the f|nger has DkILD before you pr|ck
the f|nger at the s|de of the d|sta| pha|anx. 1o ensure that the th|ck f||m |s not too
th|ck p|s app|y the b|ood to the s||de from 8LLCW |e the unders|de of the g|ass
s||de. ?ou can conLrol lL easler Lhls way lnsLead of dropplng Lhe blood.



1he usual horror sLory when 8lM x 3 ls ordered ls LhaL Lhe PC Lakes a syrlnge and
draws a venous speclmen aL end of ward rounds and proceed Lo make 3 seLs of
slldes.


9. at|ent had features of f|||ar|as|s. Consu|tant asked for b|ood f||ms for the
paras|te. 1he nC took 3 spec|mens on h|s sh|fts. What |s wrong?
uear ?ln llng,

WhaL ls Lhe brand of Lhe waLch you wear on your wrlsL?
8ecause l wlll llke Lo know how Lhe flllarla worm Lells Llme!

8ancroft|an and brug|an f||ar|as|s tend to show nocturna| per|od|c|ty, so |t |s
recommended that samp|es be co||ected between 10:00 pm and 2:00 am. up |ts a
m|dn|ght show.

So Lhe dear PC who pokes a veln afLer rounds ls noL golng Lo flnd anyLhlng.

Its a|so a f|ngerpr|ck cap|||ary spec|men and s|m||ar 1h|ck and th|n f||ms buL done
llLerally by a vamplre PC aL Lhe sLroke of mldnlghL.

13) on ILVLk
Dear L,

What |s fever?
What |s the mechan|sm beh|nd fever?
Why can some peop|e w|th no obv|ous |||ness have fever?
Why do some peop|e w|th |||ness have NC fever?
I want to LMnASI2L strong|y that the e|der|y may not have the ab|||ty to deve|op
Iever when |||. Absence of fever does not mean anyth|ng
Chee ?ong Chuan: lever ls deflned as Lhe elevaLlon of core body LemperaLure above
normal. ln normal adulLs, Lhe average oral LemperaLure ls 37 degrees Celslus.

1he febrlle response ls a complex physlologlc reacLlon Lo dlsease lnvolvlng a
cyLoklne-medlaLed rlse ln body LemperaLure and generaLlon of varlous acuLe phase
reacLanLs. lever ls Lhus consldered a hallmark of lMMunL S?S1LM AC1lvA1lCn,
resulLlng ln a regulaLed rlse ln body LemperaLure. So whaL happens ls LhaL
exogenous pyrogens from lnfecLlous agenLs, Loxlns, Lumours lnduce producLlon of
pro-lnflammaLory cyLoklnes, such as lnLerleuklns, 1nl whlch subsequenLly enLer Lhe
hypoLhalamlc clrculaLlon and sLlmulaLe release of local prosLaglandlns(Lhls ls where
our anLlpyreLlcs and nSAlu exerL Lhelr effecLs). 1he body wlll Lhen reacL Lo rlse Lhe
LemperaLure Lo Lhls new Lhermal seL polnL(manlfesLed by chllls and shlverlng).

Why do some people wlLh lllness have no fever? l can observe LhaL response Lo
fever varles wlLh age. Llderly paLlenLs especlally are unable Lo regulaLe Lhelr body
LemperaLure Lo Lhe same degree as young adulLs. rof Wong had relLeraLed many
Llmes LhaL older paLlenLs wlLh serlous lnfecLlons have subsLanLlal prevalence of a
pyrexla or LCWL8 febrlle responses! uon'L be surprlsed Lo see hypoLhermla lnsLead
ln full blown sepsls ln Lhls group of paLlenLs. lever ls also consldered Lo be an
lmporLanL hosL defence mechanlsm, hence ln Lhose who are lmmunocompromlsed
l.e Plv, paLlenLs recelvlng sLerold Lherapy, neuLropenlc paLlenLs, due Lo Lhe lnablllLy
Lo mounL an adequaLe lmmune response, mlghL noL glve you Lhe LexLbook febrlle
response LhaL you would have expecLed. l can Lhlnk of a few examples where
paLlenLs who are well buL developlng fever.

1) 1ransfuslon assoclaLed fever. Agaln, due Lo acLlvaLlon of Lhe lmmune sysLem
agalnsL anLlgen on Lhe donor blood
2) urug lnduced, probably affecLs Lhe ablllLy of Lhe body Lo dlsslpaLe heaL, or
Lhrough lmmune sysLem acLlvaLlon, serum slckness, allergy
3) lacLlLlous fever

rof : dlfference beLween fever and hyperLhermla


rof : uear ?ln Llng,

l haLe all Lhese deflnlLlons as my 8AM ls slmply Loo small Lo process Lhem. l Lhlnk of
lLvL8 as a problem buL you are slLLlng for exams and hence sLuck ln Lhe sysLem.

DLIINI1ICNS
IUC>38.3C [>101.8I], durat|on >3 weeks, d|agnos|s uncerta|n after 3 days |n
hosp|ta| or "three outpat|ent v|s|ts"!! 1hls ls close Lo our old deflnlLlon.

nCSCCCMlAL luC-hosplLallzed paLlenLs, >38.3C [>101.8l], dlagnosls uncerLaln
afLer 3 days and lnfecLlon noL presenL or lncubaLlng on admlsslon

lMMunL-uLllClLn1 (nLu18CLnlC) luC- >38.3C [>101.8l], >3 days, neuLrophll
counL <300/mm3.

Plv-8LLA1Lu luC-Plv paLlenLs, >38.3C [>101.8l], duraLlon >3 weeks for
ouLpaLlenLs or ">3 days for lnpaLlenLs"
1he era of hlgh Lechnology has changed Lhe goalposLs conslderably, noLe lnpaLlenLs
now are 1P8LL days Lo a dlagnosls. WlLh every scan Lhrown ln from L1 C1 Lo M8l, 3
days ln Lhe luLAL hosplLal appears enough.

lLvL8, n?u-perslsLenL fever LhaL has noL yeL meL Lhe deflnlLlon for luC.

ln Lhe PlS1C8?
-Lhe paLLern and duraLlon of fever,
-Lhe assoclaLed sympLoms (cough, dyspnea, hemopLysls, chesL paln, dlarrhea,
abdomlnal paln, dysurla, ureLhral dlscharge, hemaLurla, neck sLlffness, headache),
-any rash (palpable purpura, exanLhem),
-any exposure (food, waLer, planLs, anlmals, lnsecLs, lnfecLed human secreLlons),
-welghL loss, nlghL sweaLs,
-Lravel hlsLory, sexual hlsLory, Plv rlsk facLors, lmmunlzaLlons,
-pasL medlcal hlsLory (rheumaLologlc dlsorders, mallgnancy, alcohol),
-medlcaLlons
are ALL C8uClAL.

P?SlCAL exam-
vlLals (Lachycardla, Lachypnea, hypoLenslon, fever, hypoxemla),
oral ulcers, lymphadenopaLhy,
nuchal rlgldlLy,
resplraLory and cardlac examlnaLlon (murmurs),
Lemporal arLery,
abdomlnal examlnaLlon (hepaLosplenomegaly),
prosLaLe examlnaLlon,
skln leslons (morphology, dlsLrlbuLlon), lnsecL blLe marks,
[olnL examlnaLlon

Always Lhlnk of:

lnlLC1lCnS-18 (pulmonary, exLrapulmonary, mlllary),
abscess (llver, splenlc, perlnephrlc, psoas, dlverLlcular, pelvls), osLeomyellLls,
endocardlLls

nLCLAS1lC-hemaLologlc (lymphoma, leukemla, mulLlple myeloma,
myelodysplasLlc syndrome), solld Lumors (renal cell, hepaLoma)

CCLLACLn-vASCuLA8-vascullLls (glanL cell arLerlLls, SLlll's dlsease, polyarLerlLls
nodosa, 1akayasu's arLerlLls, Wegener's granulomaLosls, mlxed cryoglobullnemla),
lupus, rheumaLold arLhrlLls

u8uCS-anLlmlcroblals (sulfonamldes, penlcllllns, nlLrofuranLoln, anLlmalarlals),
anLlhlsLamlnes, anLlepllepLlcs (barblLuraLe, phenyLoln), nSAlus/ ASA,
anLlhyperLenslves (hydralazlne, meLhyldopa), anLlarrhyLhmlcs (qulnldlne,
procalnamlde), anLlLhyrold, lodldes, qulnlne, llllclL (cocalne)

unCCMMCn CAuSLS Cl luC-
endocrlne (hypoLhalamlc dysfuncLlon, hyperLhyroldlsm, pheochromocyLoma,
adrenal lnsufflclency),
lnfecLlons (denLal abscess, lepLosplrosls, pslLLacosls, melloldosls, syphllls,
gonococcemla, heredlLary perlodlc fever syndromes (famlllal MedlLerranean fever,
alcohollc hepaLlLls, hemaLoma, facLlLlous fever

ls do noL forgeL Lhe good old CLASSlC uLllnl1lCn (1961)->38.3C [>101.8l],
duraLlon >3 weeks, dlagnosls uncerLaln afLer 7 days of lnvesLlgaLlon ln hosplLal

rof : Mallgnancles have now superseded lnfecLlons as Lhe mosL common cause of
fever of unknown orlgln (luC). uld you know Lhls?
ln Lhe pasL lnfecLlous dlseases were Lhe mosL common eLlology of luC, and
neoplasms consLlLuLed Lhe second mosL frequenL caLegory. 1hls shlfL from lnfecLlous
Lo mallgnanL eLlology as Lhe mosL frequenL cause of luC ls relaLed Lo several
facLors.

llrsLly, due Lo Lhe wldespread lnLroducLlon of compuLed Lomography (C1) and
magneLlc resonance lmaglng (M8l), many lnLra-abdomlnal causes of lnfecLlon are
dlagnosed early and Lherefore do noL meeL Lhe deflnlLlon of luC. Sub phrenlc
abscesses, pelvlc paLhologles and even slnus lnfecLlons well hldden from Lhe
cllnlclan ls noL exposed clearly.

Secondly, radlonucleoLlde lmaglng sLudles, LhaL ls, lndlum scans, galllum scans, and
bone scans, have been useful ln ldenLlfylng occulL mallgnancles undeLecLable by
oLher means.

now L1 C1 has made deLecLlon of boLh well hldden lnfecLlons and mallgnancles
much easler.
rof : lymphoma ls Lhe mosL common eLlology of neoplasLlc fever of
underdeLermlned orlgln. 1he paLhophyslology of Lumor-lnduced fever may be due
Lo several mechanlsms of whlch release of cyLoklnes from Lumor cells or Lumor
necrosls facLor and lnLerleukln-1, necrosls of Lumoral Llssue, all conLrlbuLe.
l cannoL reslsL asklng you, WhaL ls Lhe Naproxen cha||enge ln luC? ?

1PL nSAlu naproxen ls very effecLlve ln suppresslng Lumor fever and Lhls properLy
may be useful ln elucldaLlng susplclon of cancer ln paLlenLs wlLh prolonged,
undlagnosed fever.

Naproxen IS 1nL c|ass|ca||y touted agent for suppress|ng tumor fever due to |ts
un|que ab|||ty to suppress tumora| cytok|nes |n preference over |nfect|ous
cytok|nes.

Whlle Lhe naproxen challenge" may be useful ln evaluaLlng prolonged fever
suspecLed Lo be of neoplasLlc orlgln, lL musL be uLlllzed ln Lhe conLexL of a Lhorough,
cllnlcally-drlven assessmenL.

14) NMS

A 66-year-old male was hosplLallzed for lncreaslngly aggresslve behavlor. Pe had no
prlor psychlaLrlc admlsslons. Cn Lhe day of admlsslon afLer he susLalned a fall, a C1
scan of Lhe braln revealed a subarachnold hemorrhage aL Lhe rlghL superlor sulcus
and a posslble hemorrhaglc conLuslon aL Lhe lefL fronLal lobe.

Cver Lhe course of hosplLallzaLlon, Lhe paLlenL had a serles of C1 scans showlng
resoluLlon of Lhe hemorrhage.

Pe was sLarLed on olanzaplne for lnLermlLLenL aglLaLlon. Clanzaplne was LlLraLed Lo
7.3 mg dally.1en days laLer Lhe paLlenL became abrupLly somnolenL wlLh body
LemperaLure reachlng 39.7 C and severe muscle rlgldlLy ln boLh upper and lower
exLremlLles. Pe had severe dlaphoresls and flucLuaLlon of blood pressure and pulse.

LaboraLory daLa revealed elevaLlon of whlLe blood cells Lo 14800 k/L, creaLlne
phosphoklnase Lo 2800 u/L (normal < 174 u/L), and mlld elevaLlon of serum alanlne
and asparLaLe amlnoLransferase. M8l of Lhe braln, CSl sLudles, and chesL radlograph
were unremarkable.

WhaL ls Lhe dlagnosls?
WhaL wlll you do now?
aLhophyslology fr Medscape

'' 1he mosL wldely accepLed mechanlsm by whlch anLlpsychoLlcs cause neurolepLlc
mallgnanL syndrome ls LhaL of dopam|ne D2 receptor antagon|sm. ln Lhls wldely
accepLed model, cenLral u2 recepLor blockade ln Lhe hypoLhalamus, nlgrosLrlaLal
paLhways, and splnal cord leads Lo lncreased muscle rlgldlLy and Lremor vla
exLrapyramldal paLhways.

PypoLhalamlc u2 recepLor blockade resulLs ln an elevaLed LemperaLure seL polnL
and lmpalrmenL of heaL-dlsslpaLlng mechanlsms. erlpherally, anLlpsychoLlcs lead Lo
lncreased calclum release from Lhe sarcoplasmlc reLlculum, resulLlng ln lncreased
conLracLlllLy, whlch can conLrlbuLe Lo hyperLhermla, rlgldlLy, and muscle cell
breakdown.

8eyond Lhese dlrecL effecLs, u2 recepLor blockade mlghL cause neurolepLlc
mallgnanL syndrome by removlng Lonlc lnhlblLlon from Lhe sympaLheLlc nervous
sysLem. 1he resulLlng sympaLhoadrenal hyperacLlvlLy and dysregulaLlon leads Lo
auLonomlc dysfuncLlon. 1hls model suggesLs LhaL paLlenLs wlLh basellne hlgh levels
of sympaLhoadrenal acLlvlLy mlghL be aL lncreased rlsk. Whlle Lhls has noL been
proven ln conLrolled sLudles, several such sLaLes have been proposed as rlsk facLors
for neurolepLlc mallgnanL syndrome.''
D|agnost|c features of NMS:

neurolepLlcs wlLhln 1 Lo 4 weeks.
PyperLhermla (above 38).
Muscle rlgldlLy lead plpe.
llve of Lhe followlng:

Changed menLal sLaLus.1achycardla.PypoLenslon or
hyperLenslon.1remor.lnconLlnence.ulaphoresls (excesslve sweaLlng) or slalorrhoea.
lncreased creaLlne phosphoklnase (Ck) or urlnary myoglobln.
MeLabollc acldosls.LeukocyLosls.
Lxcluslon of oLher lllnesses (neuropsychlaLrlc, drug-lnduced, sysLemlc).

rof : Pave you heard of 'an exLreme arklnson's crlsls' ?

lL may be posslble LhaL nMS ls as an exLreme parklnsonlan crlsls resulLlng from
overwhelmlng blockade of dopamlne paLhways ln Lhe braln.

ln Lhls vlew, nMS resembles Lhe parklnsonlan-hyperLhermla syndrome LhaL can
occur ln arklnson's dlsease paLlenLs followlng abrupL dlsconLlnuaLlon
or loss of efflcacy of dopamlnerglc Lherapy, whlch can be LreaLed by relnsLlLuLlng
dopamlnerglc agenLs.

Lvldence Lo supporL Lhls vlew lncludes:

- arklnsonlan slgns are a cardlnal feaLure of nMS

.- WlLhdrawal of dopamlne agonlsLs preclplLaLes Lhe syndrome.

- All Lrlggerlng drugs are dopamlne recepLor anLagonlsLs.

- 8lsk of nMS correlaLes wlLh drugs' dopamlne recepLor afflnlLy.

- uopamlnerglc agonlsLs may be an effecLlve LreaLmenL.

- Leslons ln dopamlnerglc paLhways produce a slmllar syndrome.

- aLlenLs wlLh nMS have demonsLraLed low cerebrosplnal fluld concenLraLlons of
Lhe dopamlne meLabollLe homovanllllc acld.

?ln llng: Lhls paLlenL ls llkely havlng whaL we know as a neurolepLlc MallgnanL
Syndrome due Lo Lhe Clanzaplne LhaL was [usL sLarLed Len days ago.

neurolepLlc mallgnanL sydrome ls caused by drugs causlng uopamlne recepLor
anLagonlsLs (commonly anLlpsychoLlcs) and also wlLhdrawal of uopamlne agonlsLs
(commonly anLl arklnsonlan drugs). LemperaLure regulaLlon became haywlre and
paLlenL presenLs wlLh classlc LeLrad of hyperLhermla whlch ls unable Lo be broughL
down by anLlpyrogens, 8lClul1?, menLal confuslon/somnolence/coma, and
auLonomlc dysfuncLlon (perfused sweaLlng, Lachycardla, lablle 8 and eLc). lL can
occur afLer a few days of Laklng Lhe drugs up Lo years afLer LhaL. classlcally lL occurs
wlLhln a few weeks.

Labs wlse: lncrease LoLal whlLe and v hlgh Ck, deranged Lransamlnases and decrease
|n se |ron |s c|ass|ca| for NMS.

SLopplng Lhe culprlL drug ls flrsL and foremosL. Secondly brlng down Lhe paLlenLs
LemperaLure wlLh meLhods llke coollng blankeL, hydraLlon, and medlcal Lherapy wlLh
dopamlne agonlsLs llke bromocrlpLlne can help. uanLrolene a muscle relaxanL ls
used Loo buL noL avallable ln many hosplLals. SupporLlng paLlenL's A8C ls of course
vlLal

nMS has been clalmed Lo have some slmllar geneLlc proflle as MallgnanL
PyperLhermla LhaL occurs when anaesL drugs classlcally succlnylchollne ls
admlnlsLered. MP ls auLosomal domlnanL and a drug hlsLory wlll help us wlLh
dlagnosls.

lL ls ofLen dlfflculL Lo dlfferenLlaLe SeroLonln syndrome and nMS. even more so
when seroLonln conLalnlng drugs wlll also have dopamlne anLagonlsL effecL.

SeroLonln syndrome ls due Lo a hlgh level of seroLonln ln Lhe body caused by glvlng
Lwo seroLonln conLalnlng drugs concurrenLly, glvlng Lhese drugs LgL wlLh C? 2u6/
3A4 lnhlblLors C8 glvlng a Long AcLlng drugs whlch lncrease seroLonln eg
rozac(fluoxeLlne). classlcal drugs LhaL causes SS are anLldepressanLs llke SS8l, Sn8l,
MACl-A (MACl-8 LhaL we are glvlng Lo our parklnsons dlsease paLlenLs won'L cause
LhaL effecL. l don'L know why). oLher common drugs are Aln CCn18CL drugs eg
1ramadol, fenLanyl, meperldlne, An1lLML18lCS eg Maxolon, granlseLron(kyLrll),
ondanseLron, 18l1AnS, Ll1PluM.

aLhophyslology of nMS and SS ls dlfferenL because SS does not cause
hypertherm|a by a|ter|ng the hypotha|amus setpo|nt. |t |s due to the overa||
hyperexc|tab|||ty.

1he few ways Lo dlfferenLlaLe:
1) SeroLonln syndrome causes neuromuscular exclLaLlon : hyperreflexla, myclonus,
clonus, lncrease ln bowel sounds, puplls dllaLaLlon, as opposed Lo LLAu lL
8lClul1? ln nMS.

2) Lab reuslLs of lncrease LoLal whlLe and Ck and Lransmlnases and decrease se lron
wlll polnL Lo nMS. SS less llkely

3) SS can occur lmmedlaLely afLer seroLonln conLalnlng drugs ls glven whlle nMS
mlghL occur afLer a few weeks.

Mx of SS : dlazepam for Lhe hyperexclLablllLy, lnLubaLlon and sedaLlon may be
needed. anLl seroLonerglc drug llke cyprohepLadlne can be glven.

ur Pu : neurolepLlc mallgnanL-llke syndrome (nMLS)

WlLhdrawal or dose reducLlon of levodopa ln paLlenLs wlLh arklnson's dlsease (u)
has been reporLed Lo preclplLaLe a poLenLlally faLal syndrome closely resembllng
neurolepLlc mallgnanL syndrome (nMS). 1hls syndrome ls referred Lo as neurolepLlc
mallgnanL-llke syndrome (nMLS) and parklnsonlsm-hyperpyrexla syndrome by
some auLhors.

Cllnlcal feaLures of nMS and nMLS are very slmllar and lnclude hlgh fever, marked
rlgldlLy, alLered consclousness, leukocyLosls, auLonomlc dysfuncLlon, rhabdomyolysls
wlLh elevaLed serum creaLlne klnase (Ck) levels, and renal fallure. nMS and nMLS
share a slmllar paLhophyslologlc mechanlsm conslsLlng of an acuLe reducLlon ln
nlgrosLrlaLal and hypoLhalamlc cerebral dopamlnerglc Lransmlsslon. ln Lhe case of
nMS, Lhe prlmary mechanlsm occurs when neurolepLlcs block u2 dopamlne
recepLors, whlle Lhe cause of nMLS ls Lhe wlLhdrawal of exogenous dopamlne. 1hls
usually occurs ln Lhe form of lLs precursor, levodopa. Cllnlcal condlLlons LhaL may
conLrlbuLe Lo Lhe occurrence of nMLS lnclude dlsLurbance ln Lhe gasLrolnLesLlnal
LracL resulLlng ln poor absorpLlon of levodopa, lnLercurrenL lnfecLlon, dehydraLlon
due Lo heaL, and poor adherence Lo medlcaLlons.

lL ls well recognlzed LhaL hlgh dleLary proLeln" lnLake can lmpalr Lhe absorpLlon of
levodopa, leadlng Lo loss of efflcacy and u sympLom flucLuaLlons. 1he amlno aclds
of Lhe proLeln may compeLe wlLh levodopa for absorpLlon ln Lhe guL and for
LransporL Lhrough Lhe blood-braln barrler. (nea|th-care profess|ona|s shou|d be
aware of the |nteract|on between |evodopa and prote|n content of entera|
nutr|t|on to avo|d the occurrence of NMLS |n pat|ents w|th D.)

1he LreaLmenL of nMLS due Lo levodopa wlLhdrawal conslsLs of supporLlve
measures, hydraLlon, and Levodopa relnLroducLlon or lncrease ln dose can be
effecLlve.

(1he Annals of harmacoLherapy 2010 SepLember, volume 44)

1S) on Card|ac 1amponade
?ln Llng,
A aLlenL was sLabbed ln 4Lh lnLercosLal space, lefL Lo sLernal border, he appears
anxlous, has marked dlfflculLy breaLhlng, wlLh paln radlaLlng down lefL arm, and Lhe
velns ln hls neck dlsLend upon lnsplraLlon.

WhaL ls Lhe ulACnCSlS?
?L: kussmaul's slgn for Cardlac 1amponade
rof : ?es lL ls a Cardlac 1AMCnAuL
-Lhls 8esulLs from accumulaLlon of fluld/blood ln Lhe perlcardlal cavlLy-Lhls
compresses Lhe hearL chambers
8ecause of poor venous reLurn Lhe neck veln has dlsLenslon= 8esulLlng ln
kussmaul's slgn.
- uLC8LASLu venous reLurn and 8LuuCLu cardlac ouLpuL


16) on 1nL LLDLkL
uear ?ln llng,

Llderly paLlenLs ofLen come Lo Lhe hyslclan wlLh abd paln. Are you aware LhaL Lhe
Classlcal hlsLory and slgns are ofLen noL seen ln Lhe elderly? MulLlple facLors
conLrlbuLe Lo Lhe dlagnosLlc dlfflculLy and hlgh lncldence of compllcaLlons seen ln
elderly paLlenLs.

lmmune funcLlon Lends Lo decrease wlLh advanclng age. Many elderly paLlenLs have
underlylng condlLlons such as dlabeLes or mallgnancy, furLher suppresslng lmmunlLy.

1o make lL worse Llderly paLlenLs ofLen have underlylng cardlovascular and
pulmonary dlsease, whlch decreases physlologlc reserve and predlsposes Lhem Lo
condlLlons such as abdomlnal aorLlc aneurysm (AAA) and mesenLerlc lschemla.

1he exam paLlenL Lyplcally has mulLlple morbldlLles cuLLlng across many dlsclpllnes.
Llderly paLlenLs also have a hlgh lncldence of asympLomaLlc underlylng paLhology.

up Lo one half of elderly paLlenLs have underlylng cholellLhlasls someLhlng l see so
ofLen, one half have dlverLlcula, and 3-10 have AAA. 8emember you see me
screenlng for Lhls ln all over 30

undersLandlng LhaL elderly paLlenLs may presenL very dlfferenLly Lhan Lhelr younger
counLerparLs also ls lmporLanL. Llderly paLlenLs Lend Lo walL much longer Lo seek
medlcal aLLenLlon Lhan younger paLlenLs as Lhey are very money consclous, and Lhey
are much more llkely Lo presenL wlLh vague sympLoms and have nonspeclflc flndlngs
on examlnaLlon.

Many elderly paLlenLs have a dlmlnlshed sensorlum, allowlng paLhology Lo advance
Lo a dangerous polnL prlor Lo sympLom developmenL.

alnless lnfarcLs for eg ls common. Llderly paLlenLs wlLh acuLe perlLonlLls are much
less llkely Lo have Lhe classlc flndlngs of rebound Lenderness and local rlgldlLy. lf Lhey
come Lo see me 1PL? A8L SlCk.

1hey are |ess ||ke|y to have fever, |eukocytos|s, or e|evated C-react|ve prote|n
|eve|. In add|t|on, the|r pa|n |s ||ke|y to be much |ess severe than expected for a
part|cu|ar d|sease.

8ecause of Lhese facLors, many elderly paLlenLs wlLh serlous paLhology lnlLlally are
mlsdlagnosed wlLh benlgn condlLlons such as gasLroenLerlLls or consLlpaLlon.

Pave a hlgh degree of susplslon and a low Lreshold for lx when managlng Lhem



17) on 8 AND MA
uear ?ln Llng Chok

over dlnner [usL now you saL ln beLween as Lhe ConsulLanL AnaesLheLlsL and l
chaLLed. 1he dlscusslon was wheLher MA ls beLLer or equlvalenL Lo SysLollc dlasLollc
pressure ln monlLorlng paLlenLs?

?ou dld noL say anyLhlng buL whaL would you had sald lf Lhls was asked of you ln
your exam? ?ou wlll have recalled LhaL l conLrlbuLed my undersLandlng of lLs
physlology. Always Lhe baslc sclences.

MA ls consldered Lo be Lhe perfuslon pressure of Lhe organs ln Lhe body.
Pence l asked her ln whaL conLexL she was referlng Lo and when she replled ln
sepLlcaemla, lL ls Lhen obvlous LhaL MA would be excellenL as we are worrled abouL
mulLl organ fallure ln sepLlcaemla.

1yplcally when Lhe MA ls greaLer Lhan 60 mmPg, LhaL ls enough Lo susLaln Lhe
organs of Lhe paLlenL. 1haL ls why Lhe ConsulLanL referred Lo LhaL flgure and used 63
as her example.

1he MA ls normally beLween 70 Lo 110 mmPg

lf Lhe MA falls below Lhls for an appreclable Llme, Lhe organs wlll noL geL enough
Cxygen perfuslon, and wlll become lschemlc.
1he MA ls Lhe average over a cardlac cycle and glves us a sllghLly beLLer ldea of
perfuslon when compared Lo looklng aL Lhe sysLollc dlasLollc pressures alone.
8ecause dlasLollc pressure ls lmporLanL you wlll noLe LhaL ln our Lyplcal calculaLlon,
Lhe dlasLollc ls mulLlplled by 2.

l also explalned LhaL ln Lhe non lCu seLLlng, we look aL sysLollc dlasLollc pressures
lnsLead because Lhe clrcumsLances are dlfferenL. ln Lhe cllnlc followlng up P1
paLlenLs for example, we are concerned abouL CvS ouLcomes. We know LhaL Lhe S8
or predlcLs Cvu among older men. As l shared ln my Lalk, Lhe sLollc 8 and lLs
varlablllLy ls very lmporLanL. 8uL as for MA, we are unsure of lLs correlaLlon wlLh
ouLcomes unllke S8 and u8 whlch ls hlghly correlaLed and beLLer predlcLs Cvu.

MA ls an alLernaLlve and preferable measuremenL Lo sysLollc blood pressure ln
monlLorlng paLlenLs aL rlsk for hypoLenslon and Lhe deLecLlon of organ
hypoperfuslon. 1hls ls a fundamenLal cllnlcal use whlch dlffers. ln sepsls for eg,
Llssue hypoperfuslon ls Lhe paLhophyslologlc endpolnL of low blood pressure, and
MA, raLher Lhan S8, ls Lhe physlologlc drlvlng force behlnd blood flow Lo organs
and Llssues. 1hls dlscusslon over dlnner could well be crlLlcal Lo your undersLandlng
and hence l wroLe Lo ensure LhaL you do undersLand.

As 8 progress|ve|y drops, a S8 of 80 mmng or |ess becomes |ess sens|t|ve and
phys|o|og|ca||y |ess appropr|ate measurement of hypotens|on than MA. 1he MA
prov|des an ob[ect|ve assessment of hypotens|on that may precede hemodynam|c
decompensat|on.

18) on 8 Var|ab|||ty

1) ln Lhe cllnlc seLLlng we are [usL Laklng a snapshoL of Lhe paLlenLs overall 8 ln 24
hours. Pow accuraLely does Lhls reflecL Lhe 24hours 8? We are movlng Lowards
home 8 monlLorlng and ambulaLory 8 monlLorlng - esp Lo deLecL masked
hyperLenslon and whlLe coaL hyperLenslon

2) Masked hyperLenslon : group of paLlenLs wlLh normal 8 ln cllnlc buL ln Lhelr dally
llves Lhelr 8 are ln Lhe hlgh slde. - easlly mlssed group of paLlenLs hence hlgh CvS
rlsk!

3) normal healLhy person has a dlp of Lhelr 8 when Lhey are sleeplng aL nlghL.
When we lose Lhls dlpplng phenomena (paLlenL who are dlabeLlc, renal fallure,
auLonomlc neuropaLhy, Laklng cyclosporln eLc) C8 WC8SL, have an early mornlng
8 surge, have hlgher CvS rlsk!

4) 8oLhwell wanLed Lo answer a quesLlon : wheLher hlgh 8 or 8 varlablllLy poses
Lhe rlsk for sLroke. 8esulLs : 8v.

3) Pence we need a drug LhaL can conLrol 8 for over 24 hours. - a long acLlng
anLlhyperLenslve.

6) ASCC1 Lrlal compared a beLa blocker (aLenolol) and a CC8, ln whlch CC8 shows
greaLer beneflL ln lowerlng sLroke. Cf course, amlodlplne was a long acLlng drug
compared Lo aLenolol

7) !nC8 guldellnes : for all paLlenLs we alm for 8 LargeL of <140/90 (Lhls lncludlng
dlabeLlc and Cku paLlenLs more Lhan 18 years old) , excepL older paLlenLs >60 years
old, Lhreshold ls hlgher aL 130/90mmPg.

8) Clder ppl wlll ofLen has a hlgher sysLollc 8 and lower dlasLollc 8.

9) Clder Leachlng : ln Cku paLlenLs keeplng 8 <140/90 ls our LargeL, and for paLlenL
wlLh proLelnurla, <133/83.

10) MosL paLlenL requlre more Lhan 1 drug use Lo conLrol 8 : besL ls CC8 and an
ACLl.

11) Amlodlplne of 10mg Cu wlll ofLen cause ankle oedema, ACLl whlch causes
efferenL vessels vasodllaLaLlon can counLer Lhls effecL.

12) ACLl Lrumps A88 ln lowerlng all cause morLallLy for all dlseases LhaL requlres 8
lowerlng excepL ln nephropaLhy. Cn1A8CL1 Lrlal shows us A88 ls as good as ACLl. ln
nephropaLhy, A88 has more beneflL.

13) 8emember Lo keep 8 around 160-180 posL sLroke, and uo nC1 LCWL8 Lhe
ulAS1CLlC Lo <110mmPg. We need Lo save Lhe penumbra.

14) Larly mornlng 8 need Lo be monlLored before Lhe paLlenL Lakes Lhelr
medlcaLlon. Larly mornlng surges are assoclaLed wlLh ACS, CvA.

13) ALrlal flbrlllaLlon - we CAnnC1 measure Lhe 8 uslng dynamap, lnaccuraLe!!
even pulse raLe wlll show a wrong readlng.

16) WrlsL monlLorlng 8 ls noL as accuraLe as Lhe prox arm 8 monlroLlng because of
smaller vessels, excepL ln one slLuaLlon. - when Lhe elderly paLlenL has obvlous
sclerosed brachlal vessels.

1he P1 elderly has afLer some Llme a shlfL ln Lhe cerebral auLoregulaLlon Lo Lhe
rlghL. Pence when we LreaL Lhem for P1 we have Lo bear Lhls ln mlnd as
overzealous reducLlon wlll brlng Lhe 8 Lo Lhe lefL of Lhe auLo regulaLlon curve and
cerebral perfuslon drops. We ofLen hear Lhe LreaLed elderly complaln of llghL
headedness, unsLeadlness or confuslon: be careful LhaL we are noL dolng more harm
here.

Pence ln elderly paLlenLs, l am happy lf Lhelr 8 ls abL 130 or so and waLch for
sympLoms llke a hawk.
1he ASCC1-8LA arm shows that ant|hypertens|ve therapy based on a "newer"
reg|men of the ca|c|um channe| b|ocker am|od|p|ne and the ang|otens|n-
convert|ng enzyme (ACL) |nh|b|tor per|ndopr|| confer s|gn|f|cant advantages over a
"trad|t|ona|" reg|men of a beta-b|ocker, ateno|o|, and th|az|de d|uret|c,
bendrof|umeth|az|de (8I2), |n terms of effects on both card|ovascu|ar morta||ty
and a||-cause morta||ty. 1he am|od|p|ne]per|ndopr|| reg|men |s a|so assoc|ated
w|th s|gn|f|cant|y fewer heart attacks and strokes.



rof : l was asked

1. why ls Lhe 1 Lo 2pm 8 mosL represenLaLlve of MA?

2. 1o make sure paLlenLs donL geL lnLo Lrouble ls lL noL beLLer Lo check Lhe Mornlng
8 surge and Lo as lL were "LreaL" LhaL and malnLaln LhaL Lo near normal raLher Lo
malnLaln Lhe 1 Lo 2 pm 8 aL normal?

AmbulaLory blood pressure monlLorlng (A8M) has shown us LhaL 24-hour average
blood pressure values bear a llmlLed correspondence wlLh offlce 8 values. 1he
correlaLlon coefflclenLs beLween offlce sysLollc 8 or dlasLollc 8 and Lhe
correspondlng 24-hour average values are rarely >0.30

ls noLe LhaL Lhls ls Average 8 whlch dlffers from MA.
1he 1 Lo 2 pm measuremenL approxlmaLes Lo Lhe Average 8, Lhls has noLhlng Lo do
wlLh Lhe MA flgures.

1he organ damage accompanylng hyperLenslon ls more closely relaLed Lo 24-hour
average Lhan Lo offlce 8. 1hls ls Lhe case regardless of wheLher Lhe damage ls ln Lhe
hearL (lefL venLrlcular hyperLrophy or dysfuncLlon), ln Lhe kldney (proLelnurla), or ln
Lhe braln (cerebral lacunae or whlLe maLLer leslons.
1he end-organ damage of hyperLenslon ls slmllarly relaLed Lo dayLlme, nlghLLlme
and 24-hour average A8s.

?our second C ls someLhlng l wlshed no one would ask!! 1hls ls because Lhls ls
where L8C ls a headache.

8 falls durlng Lhe nlghL because of Lhe reducLlon of sympaLheLlc acLlvlLy (and Lhe
lncrease ln vagal drlve). 1he early mornlng surge ln 8 "MaLches" wlLh a peak
lncldence of myocardlal lnfarcLlon, sudden deaLh, and sLroke ln Lhe mornlng hours
whlch ls why an enhanced mornlng 8 rlse ls wldely regarded as an adverse
phenomenon LhaL needs Lo be counLeracLed by Lhe 8 lowerlng effecL of LreaLmenL.
Sounds raLlonal rlghL? l Lhlnk so Loo.

Powever, no oLher evldence exlsLs LhaL mornlng 8 rlse ls rlsky, nC lnLervenLlonal
18lALS Lo booL, Lherefore, aL presenL, lLs relevance for Lhe peak mornlng lncldence
of cardlac and cerebrovascular evenLs ls only of observaLlonal daLa and speculaLlve.

lurLhermore, several oLher phenomena poLenLlally dangerous for Lhe hearL and Lhe
braln (hearL raLe, flbrlnolyLlc acLlvlLy, plaLeleL aggregablllLy, clrculaLlng
caLecholamlnes, eLc), also show peaks ln Lhe mornlng LhaL may make Lhe mornlng
8 rlse a paLhophyslologlcal cofacLor.
Cur LreaLmenL hence ls Lo homogeneously lower Lhe whole 24-hour 8 proflle, and
Lhus also wlLhouL any adverse lnLerference wlLh Lhe physlologlcal mornlng 8 rlse
unless lL ls unaccepLably hlgh. erhaps naLure has lnLended a rlse for funcLlon.

1he nocLurnal fall ln 8 can vary wldely among lndlvlduals, whlch has led
hyperLenslve sub[ecLs Lo be classlfled lnLo 2 caLegorles, le, Lhose whose nlghLLlme
average 8 falls more Lhan 10 of Lhe average dayLlme value and Lhose ln whom lL
falls less.

WlLh Lhe use of Lhls classlflcaLlon, ln hyperLenslve sub[ecLs ln whom nocLurnal 8
falls less Lhan 10 (known as nondlppers"), organ damage ls much greaLer Lhan ln
Lhose ln whom lL falls more Lhan 10 (known as dlppers"), and LhaL Lhls ls Lhe case
also for Lhe organ damage progresslon.

19) on nIS1Ck 1ak|ng
uear ?ln Llng,

Lhe hlsLory Laklng skllls are besL learnL from repeaLedly Lalklng Lo paLlenLs wlLh
dlfferenL complalns and formlng well Lrodden Lhlnklng paLhs ln Lhe mlnd as we llsLen
and enqulre. l Lry so hard every year Lo Leach Lhls Lo my sLudenLs and someLlmes lL ls
exhausLlng.

A good hlsLory ls Lruly Lhe ConducLor of Lhe orchesLra of dlagnosls, Lhe many
physlcal slgns and lnvesLlgaLlons Lhe varlous players of varled lnsLrumenLs.
SomeLlmes lL ls a humble CuarLeL wlLh a few slgns and mlnlmal lnvesLlgaLlons Lo
reach a dlagnosls buL sLlll neverLheless beauLlful llke Lhe '4 seasons'.

SomeLlmes lL requlres a full orchesLra, wlLh many compllcaLed slgns and a long llsL of
hlgh Lech scans. neverLheless lL sLlll requlres Lhe ConducLor Lo ul8LC1 lL all or Lhe
many muslclans wlll be llke headless chlckens runnlng abouL ln no parLlcular
dlrecLlon. Many of Lhe lnnocenL nalve hlsLorles and hy LxamlnaLlons presenLed by
my year3s are llke LhaL, a hlsLory LhaL has nC Lhlnklng paLh and compleLely random
plus a hy LxamlnaLlon llke a wlld man shooLlng ln Lhe dark hoplng he wlll hlL
someLhlng! Lven Lhelr lnvesLlgaLlons do noL follow any Lhlnklng sequence for Lhe
ConducLor of Lhe PlsLory has gone schlzophrenlc!!

lor my klddles ouL Lhere pls read Lhls and undersLand well. 1he PlsLory when well
Laken ls a MasLer ConducLor llke PerberL von kara[an, Slr Ceorg SolLl, Leonard
8ernsLeln, who dlrecLs hls CrchesLra wlLh flnesse, nC1 A SlnCLL lnS18uMLn1 Cu1
Cl 1unL or 1lML!

1he PlsLory when poorly Laken leads Lo a whole sequence of laughable evenLs whlch
may have serlous consequences, 8es lpsa LoqulLur!!

20) on ANGINA
uear ?L,
Why ls paln of hearL aLLack percelved ln LLl1 arm as well as ln Lhorax?
Chee ?ong Chuan : Wllllam Peberden M.u was Lhe flrsL Lo descrlbe anglna pecLorls
and subsequenLly presenLed hls flndlngs Lo Lhe 8oyal College of hyslclan. lL was a
pleasure readlng Lhe orlglnal descrlpLlon of anglna, and many of hls asLuLe
observaLlons sLlll hold Lrue unLll Loday.

rof : lL ls lmpL Lo reallse LhaL anglna does noL have a unlformly bad prognosls, LhaL
Lhe percepLlon of Lhe degree of paln does noL correlaLe well wlLh paLhology.
1he young sLudenL mlghL Lhlnk LhaL he she LhaL Lells of mlnlmal paln on Lhe scale
could be dlsmlssed as mlnor buL Lhls ls cerLalnly noL so as descrlbed above. 8uL a
SLvL8L Aln SC 8Au 1PA1 1PL A1lLn1 C8ASS ?Cu8 A8M Anu nC1 LL1 CC
would make one conslder a dlssecLlon hlghly llkely.

C?C : 1he vlsceral afferenL flbers Lravel wlLhln Lhe sympaLheLlc cardlac nerves Lo Lhe
sympaLheLlc Lrunk on Lhelr way Lo Lhe splnal cord, whlch Lhey enLer Lhrough dorsal
rooLs aL levels 11-13. 1hese vlsceral afferenLs are Lhus ln Lhe same dorsal rooLs as
Lhe somaLlc afferenLs reLurnlng from Lhe medlal border of Lhe lefL upper llmb and
lefL slde of Lhe chesL wall (look aL any sLandard dermaLome charL). lor reasons noL
well-undersLood, Lhe vlsceral paln (orlglnaLlng ln Lhe hearL) ls referred Lo Lhe
cuLaneous reglon lnnervaLed by nerve flbers LhaL enLer Lhe splnal cord aL Lhe same
levels.
rof : uear ?L,

-1he AfferenL 'paln' sensaLlon l8CM Lhe hearL ls carrled Lo splnal cord vla
S?MA1PL1lC nerves. 1haL ls why ln condlLlons wlLh auLonomlc neuropaLhy, Lhere
may be nC paln percelved aL all.
- 1hese axons enter sp|na| cord at 11-14 (maybe 1S) on the |eft s|de.
-1he aln of anglna ls referred Lo lefL slde of Lhe chesL and arm (supplled by 11
nerve) because Lhese areas send sensory lmpulses Lo same segmenLs of splnal cord
LhaL recelve cardlac afferenL flbers.
ls noLe LhaL Lhere ls much varlaLlon ln Lhe area of paln.

rof : Whlch ls Lhe MosL common slLe of coronary arLery block?
Whlch ls Lhe 2nd mosL common slLe of coronary arLery block?
C?C : 1he ma[or vessels of coronary clrculaLlon are Lhe rlghL coronary arLery(8CA)
and Lhe lefL maln coronary arLery(LMCA). 1he LMCA branches lnLo Lhe lefL anLerlor
descendlng arLery(LAu) and lefL clrcumflex arLery(Lcx). 1he 8CA on Lhe oLher hand
branches lnLo Lhe marglnal branch and posLerlor lnLer venLrlcular branch. A qulck
walk ln Lhe CCu/Lu wlll reveal LhaL anLerlor and lnferlor S1LMls are by far Lhe mosL
common! (Makes sense as Lhey are Lhe ma[or source of blood supply Lo Lhe
myocardlum). S1LMl lnvolvlng Lhe hlgh laLeral wall, lsolaLed posLerlor S1LMl, lefL
maln occluslon are noL so common! 8eferrlng Lo Lhe CuS1C-1 Lrlal LhaL recrulLed
almosL 41 Lhousand paLlenLs wlLh S1LMl, anLerlor and lnferlor S1LMl consLlLuLe 97
of all S1LMl

rof : Well done. A Lrue son of Aesculaplus. now you reallse why Lhe LCC changes of
lnferlor Ml and v1 S1 abnormallLles, Lhe concepL of 8v lnfarcLs , and AnLerlor Ml
changes wlLh posslble Wellens precedlng lf hlgh ls SC much emphaslzed ln my
sesslons wlLh you all.
unrecognlzed myocardlal lnfarcLlon ln paLlenLs aged 33 and older ls noL uncommon.
A hlgh lncldence of unrecognlzed myocardlal lnfarcLlon ls due Lo 'aLyplcal' cllnlcal
presenLaLlon of Lhe lnfarcLlon wlLh lncreaslng age.

Such an aLyplcal presenLaLlon lncludes Lhe absence of chesL paln and Lhe presence
of non-chesL paln, parLlcularly locallzed ln Lhe neck, back, [aw, or head, followed by
non-paln sympLoms such as weakness, sweaLlng, nausea, dyspnoea, or cough.

Women are a subgroup wlLh a greaLer llkellhood of aLyplcal presenLaLlon.
1he sympLomaLology of myocardlal lnfarcLlon, lncludlng boLh paln and non-paln
sympLoms, may be affecLed by rlsk facLors, such as smoklng, hyperLenslon, dlabeLes,
and hypercholesLerolaemla.
1here ls also a lower frequency of chesL paln among Lhose evolvlng non-C Lhan
among Lhose evolvlng C-wave lnfarcLlon.
llnally, lsolaLed lnfarcLlons of lnferlor or laLeral slLe more ofLen have aLyplcal
presenLaLlon compared wlLh anLerlor lnfarcLlons.



rof : uear ?L

whaL ls Lhe SPCuLuL8-PAnu S?nu8CML ln relaLlon Lo CPu?
?L: "SPS ls a complex reglonal paln syndrome causlng a palnful uL due Lo Lhe
dlsLurbance of Lhe sympaLheLlc nerve supply,(reflex sLlmulaLlon) commonly seen
afLer hemlplegla / Ml. cllnlcally paLlenL wlll have palnful shoulder wlLh llmlLed
moLlon wlLh swelllng, colour changes and sLlffness.elbow ls rarely lnvolve. Lhere wlll
be colour changes of Lhe hands, followed by flexlon deformlLy,and Lrophlc changes
of Lhe skln"


21) on LIVLk DISLASL
uear ?L,
A 41-years-old man has a hlsLory of drlnklng 1 Lo 2 llLers of Loddy per day for Lhe
pasL 20 years. Llfe ls hard ln Lhe esLaLes.

Pe had numerous eplsodes of nausea and vomlLlng ln Lhe pasL 3 years. Pe now has
prolonged vomlLlng, followed by masslve hemaLemesls.

Cn physlcal examlnaLlon hls vlLal slgns are:
1 36.9C, 110/mln, 88 26/mln, and 8 80/40 mm Pg lylng down.

WhaL does Lhls baslc lnfo Lell you?
WhaL ls Lhe paLhophyslology behlnd Lhls?
WhaL wlll you lmmedlaLely do?

ulse ls regular and no murmurs noLed and hls lungs are clear Lo ausculLaLlon. 1here
ls no abdomlnal Lenderness or dlsLenslon and bowel sounds are presenL.

8 showed normal sLools

WhaL ls Lhe mosL llkely dlagnosls?
rof : ln llver dlsease Lhere ls uecreased acLlvaLlon of vlLamln k-dependenL enzymes:
vlLamln k ls faL-soluble requlrlng blle secreLlon (for faL emulslflcaLlon ln Lhe
lnLesLlne) for absorpLlon.

CholesLaLlc llver dlsease can resulL ln a lack of vlLamln k, wlLh decreased producLlon
of vlLamln k-dependenL enzymes (facLors ll, lvll, x and x) and a vlLamln k-
responslve coagulopaLhy. 8emember also LhaL lmporLanL lnhlblLors of Lhe
coagulaLlon cascade, roLeln C and proLeln S, are also vlLamln-k dependenL.

roducLlon of abnormal facLors: Abnormal flbrlnogen molecules (dysflbrlnogenemla)
ls a feaLure of some llver dlseases, such as hepaLomas and acuLe and chronlc llver
dlsease. 1he abnormal flbrlnogen cannoL form flbrln or cannoL polymerlze, resulLlng
ln lnadequaLe cloL formaLlon and hemorrhage
A LherapeuLlc Lrlal of vlL k ls ofLen glven afLer blood ls Laken for CoagulaLlon proflle.
8uL Lhere are no randomlsed cllnlcal Lrlals on Lhe beneflLs or harms of vlLamln k for
upper gasLrolnLesLlnal bleedlng ln paLlenLs wlLh llver dlseases. 1here ls no evldence
Lo recommend or refuLe Lhe use of vlLamln k for upper gasLrolnLesLlnal bleedlng ln
paLlenLs wlLh llver dlsease.
ur Pu : MosL emergency physlclans are less aware of Wernlcke encephalopaLhy",
and always mlsdlagnosls as posLerlor clrculaLlon sLroke".

Wernlcke encephalopaLhy, Lhe consequence of Lhlamlne deflclency, ls characLerlzed
by dlsorders of ocular moLlllLy, galL aLaxla, and dlsLurbances of consclousness. 1he
same Lrlad of slgns also encounLered commonly ln occluslon of Lhe rosLral basllar
arLery".


22 ) CN 8L1A 8LCCkLkS
uear ?ln LlnC,

A 73 year old porLly female has been on follow up for years wlLh mlld P1 and uM
conLrolled wlLh oral medlcaLlon. She has dyspnoea on exerLlon and lefL venLrlcular
sysLollc dysfuncLlon ls noLed on LCPC. Per anglo showed mlld non crlLlcal leslons.
She was progresslvely dyspnoelc on cllmblng sLalrs buL noL aL resL. Per renal
funcLlon ls normal.

1he paLlenL ls already on 8amlprll and lurosemlde.
Whlch drug/s may lmprove Lhe paLlenL's sympLoms and prognosls?

Amlodarone
dlgoxln
dllLlazem
8lsoprolol
lsosorblde dlnlLraLe
vasLeral
Coenzyme C10
?L : 1) 8eLa blocker ln hearL fallure. 1he sympaLheLlc paLhway and Lhe
neuroendocrlne paLhway are Lhe Lwo culprlLs ln Lhe cllnlcal course of hearL fallure.
1he neuroendocrlne paLhway can be halL by an ACL- l and beLa blockers can reduce
Lhe sympaLheLlc acLlvaLlon on Lhe hearL and slows down Lhe progresslon of hearL
fallure. Ma[or Lrlals are ML8l1-Pl and Cl8lS-ll Lrlal. 1he paLlenLs wlll ofLen feel worse
before Lhey feel beLLer. upLlLraLed durlng every follow up ls lmporLanL as long as
paLlenL ls able Lo LoleraLe.

2) beLa blockers are sLlll used ln raLe conLrol for aLrlal flbrlllaLlon/Sv1. lL can also
sLablllse a prolonged C1 prevenLlng 1orsades.

3) ropanolol commonly used as prophylaxls for esophageal varlces.

rof : uear ?ln Llng,

besldes whaL you had menLloned above, pls also remember

AnxleLy
Claucoma
Mlgralne
1hyroLoxlcosls and lLs assoclaLed erlodlc Pypokalaemlc paralysls


Can you Lell me Lhe conLralndlcaLlons?
A8CDLIGn
Asthma, AC, Ath|etes
8radycard|a, bronchospasm
C opd
DM, dys||p|d|m|a, Dreams
LD, extrem|t|es
Ietus, fat|gue
Ger|atr|cs
nypotens|on, heart b|ock, hypothyro|d, hypog|ycaem|a, hyperka|em|a

23) CN ALI1A1ICNS
uear ?ln llng,

A common cllnlcal problem LhaL we see ln cllnlcs ls Lhe young person presenLlng
wlLh complaln of 'palplLaLlons a few days ago' .

An 18 year old woman had repeaLed eplsodes of breaLhlessness and palplLaLlons, no
glddlness, buL lasLlng abouL 20 mlnuLes and resolvlng gradually.

Commonly on examlnaLlon Lhere are no abnormal physlcal slgns. noLhlng!
no cllck murmur, no long flngers. no vlLlllgo, no golLre.

Pow do you Lhlnk ouL as Lo Lhe mosL llkely cause of Lhese feaLures?

ls lL posslble drug abuse by young spolled adulLs?

WhaL abouL panlc dlsorders?

Ppw and when do we suspecL paroxysmal supravenLrlcular Lachycardla?

Cr lL posslble LhaL a personallLy dlsorder ls Lhe cause?

And how abouL LhyroLoxlcosls sans golLre?
?L : yes palplLaLlons ls a common complalnL we ofLen see durlng our dally work and
we also ofLen hear of our young frlends havlng appLs for a PolLer due Lo recurrenL
palplLaLlons Loo.

Cllck murmur wlll suggesL a MlLral valve prolapse, also know as 8arlow's dlsease,
occurs more ln young female ln whlch Lhe Lhere's domlng/ prolapse of usually Lhe
posLerlor cusp of Lhe Mv back lnLo Lhe aLrlum durlng sysLole. Lhe Lenslng of Lhe
mlLral valve durlng Lhls cycle caused Lhe Cllck! followed by a mld or laLe sysLollc
murmur. aLrlal flbrlllaLlon or oLher Sv1 can occur due Lo Lhls- causlng Lhe complalnL
of palplLaLlons Lhe ls uusally self llmlLlng.

Long flngers wlll suggesL Marfan's syndrome, whlch ls also assoclaLed wlLh Mv. A8
rarely causes arrhyLhmlas.

vlLlllgo ls due Lo an auLolmmune process, anoLher auLolmmune process l can Lhlnk
of LhaL causes palplLaLlons ls graves dlsease, common ln Lhe young. Lhey would
presenL wlLh or wlLhouL a golLer as well. Lhyrold anLlbodles, 14 and 1SP are
lmporLanL lnvesLlgaLlons as palplLaLlons cannoL be cure wlLhouL Laklng care of Lhe
LhyroLoxlc sLaLe.

urug abuse ls common, sLudenLs Laklng ampheLamlnes, caffelnaLed producLs Lo sLay
awake Lo sLudy, energy drlnks saLuraLed wlLh glucose and caffelne, sporLs or healLh
producL whlch promlses vlLallLy, Lhyroxlne LableLs Laken by young glrls for welghL
loss...v common, causlng LhyroLoxlc sans golLer l supposed?
8Cl : urug abuse can cause palplLaLlons buL Lhere wlll be oLher sympLoms. ?oung
glrls pop ampheLamlne llke drugs Lo lose welghL and palplLaLlons ls common buL
Lhere ls anorexla, lnsomnla as well. Look aL Lhe lC plcLure. Any mark change? urugs
of abuse slmllarly has oLher feaLures eg dehydraLlon ls common. Speak Lo parenLs.

ersonallLy dlsorders Lend Lo be chronlc llke me la and wlll noL have a shorL hlsLory.
Many aspecLs of llfe wlll be affecLed by personallLy dlsorders.

PyperLhyroldlsm ln young people Lyplcally have many feaLures unllke Lhe elderly
where Al may be Lhe only flndlng. WelghL loss, lncreased appeLlLe, mensLrual
abnormallLles wlll be expecLed.

SV1 has sudden starts and stops. 1hat's not seen here.

anlc dlsorder ls llkely and Lhls would be Lhe worklng dlagnosls whlle we exclude Lhe
oLher posslbllLles as noLed.


24) CN CLU88ING
uear ?ln Llng,

ls know LvL8?1PlnC abouL clubblng before your exams.

llnger clubblng may occur, wlLhouL evldenL underlylng dlsease, as an ldlopaLhlc form
or as a Mendellan domlnanL LralL. ulglLal clubblng may be symmeLrlc bllaLerally, or lL
may be unllaLeral or lnvolve only a slngle dlglL.

1he speclflc paLhophyslologlc mechanlsm of dlglLal clubblng remalns unknown!! 1he
common facLor ln mosL Lypes of clubblng ls dlsLal dlglLal vasodllaLlon, whlch resulLs
ln lncreased blood flow Lo Lhe dlsLal porLlon of Lhe dlglLs.
Serr|c Suthesh: CurrenLly Lhe mosL accepLed P?C1PLSlS ls LhaL lL ls caused by
laLeleL derlved growLh facLor, megakaryocyLes Lravel Lo Lhe lungs Lo fragmenL and
become plaLeleLs, lf Lhls process doesnL occur, Lhey geL Lrapped ln Lhe perlpheral
vessels, secreLe uCl and cause prollferaLlon of cells and flbroblasL leadlng Lo
clubblng,
1hls hypoLhesls acLually helps explaln why cyanoLlc hearL dlsease and lung dlsease
whlch dlsrupLs normal pulmonary clrculaLlon can lead Lo Lhls,
ln aLlenLs wlLh lung cancer however Lhey found vascular endoLhellum growLh
facLor LhaL ls lnvolved wlLh hyperLrophlc pulmonary osLeoaLropaLhy as well.
AlLeraLlons ln slze and conflguraLlon of Lhe clubbed dlglL resulL from changes ln Lhe
nall bed,
1. beglnnlng wlLh lncreased lnLersLlLlal edema early ln Lhe process. Look for nallfold
8ogglness.

2. As clubblng progresses, Lhe volume of Lhe Lermlnal porLlon of Lhe dlglL may
lncrease because of an lncrease ln Lhe vascular connecLlve Llssue and change ln
quallLy of Lhe vascular connecLlve Llssue, Lhls leads Lo SchamroLh's slgn

3. and subsequenLly an lncrease ln Lhe glrLh of Lhe flnger aL Lhe nallbed Llll Lhe cross
secLlonal measuremenL ls now more Lhan LhaL aL Lhe level of Lhe ul [olnL.

4. llnally Lhe classlc urumsLlck or arroL beak appearance ls seen.
(Cccaslonally Lhere are spurs of bone on Lhe Lermlnal phalanx.)


Clubblng usually develops flrsL ln Lhe Lhumb and foreflnger, and occurs ln Lhe oLher
flngers laLer. lL may be dlfflculL Lo recognlze unless Lhe sLudenL observes Lhe hands
(and feeL) carefully. 1wo slgns are characLerlsLlc of early clubblng: Lhe "floaLlng nall"
slgn and Lhe "proflle" slgn.

ln Crade 1 Lhe nall feels as lf lL ls floaLlng on a cushlon. l asked you all abouL Lhe
angle seen from Lhe slde many Llmes, wlLh clubblng, prollferaLlon of Llssue under Lhe
nall plaLe causes Lhls angle Lo lncrease Lo more Lhan 160 degrees. ln facL, Lhe angle
may be enLlrely losL and Lhe nall plaLe and skln lle ln a sLralghL llne (180-degree). As
clubblng progresses, Lhe angle exceeds 180 degrees. 8ecause Lhls can be easlly
deLecLed and preclsely deflned, Lhe sLudenL should rely on Lhls slgn when uncerLaln
lf a paLlenL's flngers are Lruly clubbed. We may debaLe over how 8oggy ls 8oggy!!!
nanSheng: MnLMCnlC for causes of CLu88lnC:

C.L.U.8.8.I.N.G, w|th the L hav|ng an extens|on of A.8.C.D.L.I

C - CyanoLlc hearL dlsease
L - Lung dlsease

Abscess
8ronchlecLasls
CysLlc llbrosls/ carclnoma
uonL say CCu
Lmpyema
llbrosls

u - ulceraLlve ColllLls + lnflammaLory 8owel ulsease(Crohn's ulsease)
8 - 8lllaLry clrrhosls
8 - 8lrLh uefecLs
l - lnfecLlve LndocardlLls
n - neoplasm(eg. Lung cancer or mesoLhelloma)
C - CasLrolnLesLlnal malabsorpLlon syndrome(Coellac dlsease)

Acropachy ls an alLernaLlve Lerm for clubblng. Acqulred clubblng ls ofLen reverslble
when Lhe assoclaLed condlLlon ls LreaLed successfully.


2S) AUSCUL1A1Ck LkCUSSICN
uear ?ln Llng,
1ell me whaL do you know abouL AusculLaLory ercusslon on phy exam?
ChesL and abdomlnal examlnaLlon ls greaLly clarlfled once you masLer Lhls
Lechnlque.

8Cl : AusculLaLory percusslon ls a meLhod of physlcal examlnaLlon whlch conslsLs
ln Lapplng llghLly Lhe manubrlum sLernl wlLh Lhe dlsLal phalanx of Lhe mlddle flnger
whlle llsLenlng over Lhe chesL wall posLerlorly wlLh a sLeLhoscope, a decrease ln
sound lnLenslLy ls usually aLLrlbuLed Lo lung abnormallLles. 1he baslc prlnclple ls LhaL
AusculLaLlon performed aL Lhe same Llme LhaL percusslon ls made, comblnlng boLh
cllnlcal meLhods.

AusculLaLory percusslon ls a senslLlve and speclflc way Lo deLecL pleural effuslon,
even when fluld amounLs are small. lL ls useful ln deLecLlng Lhe upper level of Lhe
effuslon before a Lap.
lL can also be used ln locallslng Lhe edges of Lhe abdomlnal organs.

lnLeresLlngly lL can be used ln deLecLlng fracLures of Lhe shafL of Lhe femur,
humerus, and clavlcle, Lelllng Lhe presence of a compleLe fracLure, Lhe relaLlve
poslLlon of Lhe fragmenLs, and, durlng Lhe posLoperaLlve course, Lhe developmenL of
bony unlon. 1he sLeLhoscope bell and Lhe percusslng flnger ls applled over bony
promlnences on elLher slde of Lhe fracLure and Lhe sound so ellclLed compared wlLh
LhaL produced by Lhe same procedure on Lhe normal slde. Sound alLeraLlon
consLlLuLes Lhe crlLerlon of Lhe LesL. lLch and quallLy changes resulL from free
vlbraLlon of Lhe separaLe fragmenLs and, accordlngly, slgnlfy compleLe fracLure or
lncompleLe unlon. Appreclable dlmlnuLlon ln sound lnLenslLy lndlcaLes poor
conducLlon and reflecLs absence of end-Lo-end conLacL.

ls see aLLached paper ln !AMA Aug2 1941


26) CN SnCCk
uear ?L,

l Lrled very hard Lo Leach you all Loday regardlng Lhe paLhophyslology of
Pypovolemlc shock and recognlslng lL early. lmpendlng shock ls characLerlzed by a
ralsed hearL raLe caused by caLecholamlne release ln an aLLempL Lo malnLaln cardlac
ouLpuL when sLroke volume decreases due Lo dlmlnlshed venous reLurn.

kemember the rap|d 8U1 thready u|se!! Look|ng and fee||ng the hands te||
vo|umes!
C o|our
C app||ary return
1 emperature
V o|ume of pu|se
k ate of pu|se
U r|ne output
Lveryone of Lhese slgns Lells of compensaLory mechanlsms Laklng place!
1he Skln changes are Lhere for all Lo see lf only you observe.
1here are slgns of decreased skln perfuslon ln early shock due Lo perlpheral
vasoconsLrlcLlon. !usL hold and feel Lhe hands, a cold clammy hand ls uAnCL8
manlfesLed by a prolonged caplllary reflll (>2 seconds), cool moLLled exLremlLles and
pallor.

(8radycardla ls however a preLermlnal slgn caused by hypoxla and acldosls. 1haL ls
near end game and Loo laLe! We see Lhls ln paLlenLs abouL Lo dle. )

PypoLenslon (sysLollc blood pressure less Lhan 80 or 90 mm Pg) ls a very laLe slgn of
shock. 1he body wlll do lLs besL Lo compensaLe Lo ensure LhaL cerebral and cardlac
perfuslon ls malnLalned.

A reducLlon ln sLroke volume may noL cause a decrease ln blood pressure lf Lhere ls
an adequaLe lncrease ln sysLemlc vascular reslsLance and hearL raLe LhaL can
compensaLe for Lhe blood loss. ln early shock and ln splLe of havlng a normal blood
pressure, organ and Llssue perfuslon may be compromlsed.

As shock advances, Lhe compensaLory mechanlsms fall and profound hypoLenslon
Lhen occurs. 1haL ls when Lhe nurse calls you!!
ls always remember Lhe formula for 8 and you wlll undersLand Lhe mechanlsm for
compensaLlon. ?ou musL also remember Lhe Shock lndex Lo plck up Lhe lmpendlng
shock early.

1he cllnlcal slgns are easy Lo recall once you have Lhe 8 formula ln your mlnd.




8ackground:
CompensaLory SLage of Shock
uurlng Lhe compensaLory sLage of shock, Lhe body Lrles Lo overcome Lhe effecLs of
blood loss. hyslologlcal, neural, hormonal, and blochemlcal reacLlons are used Lo
correcL Lhe lmbalances. Cne of Lhese mechanlsms ls hypervenLllaLlon Lo help
lmprove oxygen flow Lo Lhe cells ln order Lo neuLrallze Lhe newly acldlc condlLlons.

AnoLher mechanlsm used ls Lhe caLecholamlne response Lo lncrease Lhe body's
hearL raLe Lo lncrease blood pressure.

A Lhlrd mechanlsm ls Lhe renln-angloLensln response. uurlng Lhls response, a
hormone called vasopressln ls released lnLo Lhe bloodsLream Lo reLaln fluld and
Lrlggers vasoconsLrlcLlon.
AnoLher hormone parLlclpaLlng ln Lhls rescue mechanlsm ls vasopressln, lL ls
secreLed by Lhe posLerlor plLulLary gland ln response Lo 2 facLors, prlmarlly
osmolarlLy and secondly blood pressure. 1he plummeLlng blood pressure ls deLecLed
by Lhe pressure recepLor e.g caroLld slnus and aorLlc body whlch slgnal Lo Lhe
hypoLhalamus' paravenLrlcular nucleus and also Lhe supraopLlc nucleus Lo secreLe
AuP/vasopressln

1here ls 2 subLypes of vasopressln recepLors: v1 ls locaLed aL Lhe smooLh muscle
whlch cause vasoconsLrlcLlon (hence lncrease Lhe 18 and malnLaln Lhe 8) and v2
aL Lhe kldney dlsLal convoluLed Lubule and collecLlng Lubule whlch lncrease
reabsoprLlon of waLer. lL was flrsL named vasopressln because of lLs effecL ln
vasoconsLrlcLlon.



8enal funcLlon wlll be sacrlflced on Lhe alLar of cerebral perfuslon!
Cllgurla (urlne ouLpuL < 0.3 ml/kg/ h ln adulLs ) reflecLs a decreased glomerular
fllLraLlon raLe due Lo afferenL arLerlolar vasoconsLrlcLlon ln response Lo sympaLheLlc
sLlmulaLlon and renln-angloLensln sysLem acLlvaLlon when volume depleLlon occurs.
Make sure LhaL your paLlenL has aL leasL 1ml a mln of urlne ouLpuL.
urlne ouLpuL ls absenL ln severe shock. ZL8C!

1he 8raln ls klng. 1he braln, and hearL have Lhelr blood supply proLecLed aL Lhe
expense of decreased blood supply Lo oLher organs.

ln early sLages Lhere are no changes ln menLal sLaLus. 8uL as shock progresses, Lhe
compensaLory mechanlsms fall and slgns of decreased cerebral perfuslon such as
aglLaLlon, confuslon, drowslness and coma appear.

rogresslve SLage of Shock
lf shock progresses, damage Lo Lhe body ls more severe and may even be
lrreverslble. Cellular funcLlon deLerloraLes, anaeroblc meLabollsm leads Lo an
lncrease ln meLabollc acldosls, and Lhe compensaLory mechanlsms are noL able Lo
malnLaln Lhe balance requlred Lo proLecL Lhe organs.

8efracLory SLage of Shock
lf Lhe cause of shock cannoL be flxed, Lhe body wlll lnevlLably enLer Lhe lasL sLage of
shock. uurlng Lhls sLage, Lhe organs fall and lead Lo deaLh. Cne of Lhe mosL
lmporLanL facLors ln recognlzlng Lhe dlfferenL sLages of shock ls Lo prevenL
progresslon Lo Lhls flnal sLage.


27) CN C1 SCANS
uear ?ln Llng,

C1 scans have been a Lremendous advance ln our dlagnosLlc klL.
lL ls however noL enLlrely wlLhouL rlsks.

Can you elaboraLe on Lhe conLralndlcaLlons and rlsks lnvolved?
l wanL all sLudenLs Lo be aware of Lhls. ls see carefully Lhe Cx8 equlvalenLs. 1hen
we wlll be more mlndful when orderlng C1s. lf a paLlenL needs lL, by all means do lL!
8uL noL lf you are dolng lL for your own lnLeresL






Ask yourself honesLly, does your paLlenL requlre a C1 and ls Lhe ouLcome beneflclal
Lo hlm vs Lhe long Lerm rlsk? 1hen declde on Lhe lnvesLlgaLlon
AnoLher way of helplng us undersLand ls Lo see lL from Lhe equlvalenL of a year's
background radlaLlon.
8adlaLlon ls measured ln unlLs called mllllsleverLs (mSv). ulfferenL Lypes of C1 scan
lnvolve dlfferenL amounLs of radlaLlon:
C1 scan of Lhe head - 1.4 mSv, whlch corresponds Lo seven-and-a-half monLhs'
worLh of background radlaLlon
C1 scan of Lhe chesL - 6.6 mSv, or Lhree years' worLh of background radlaLlon
C1 scan of Lhe whole body - 10 mSv, whlch corresponds Lo four-and-a-half years'
worLh of background radlaLlon.

newer machlnes wlLh beLLer sofLware uses less radlaLlon Lo obLaln Lhe same lmage,
how old ls your hosplLals C1 scanner makes a dlfference
We are consLanLly exposed Lo radlaLlon from a number of sources, lncludlng
radloacLlve maLerlals ln our envlronmenL, radon gas, and cosmlc rays from ouLer
space. 1hls ls called background radlaLlon and lL varles across Lhe counLrles.

1he average man ls exposed Lo abouL 3 mSv (mllllsleverLs) of radlaLlon from naLural
sources over a year. Much of Lhls exposure ls from radon, a naLural gas.

1he earLh's aLmosphere blocks some cosmlc rays, Lhus llvlng aL a hlgh alLlLude
lncreases a person's exposure - a 10-hour alrllne fllghL lncreases cosmlc ray
exposure by abouL 0.03 mSv.

Smoklng a pack of clgareLLes a day exposes Lhe smoker Lo an exLra 33 mSv per
year!!!
ln summary, because radlaLlon exposure from all sources AuuS up over a llfeLlme,
and radlaLlon can lncrease cancer rlsk, lmaglng LesLs LhaL use radlaLlon should only
be done for a good reason.

ln many cases, non radlaLlon procedures llke ulLrasound or M8l may be used esp ln
Lhe younger paLlenLs. 8uL lf Lhere's a reason LhaL an x-ray or C1 scan ls Lhe besL lx,
Lhe paLlenL musL be helped more Lhan Lhe small dose of radlaLlon can hurL.


ur Pu : hLLp://www.ncbl.nlm.nlh.gov/pubmed/23048079
Mark Otto Baerlocher, MD, Murray Asch, MD, and Andy Myers, MDCM
Metform|n |s excreted by the k|dneys
MeLformln ls used ln Lype 2 dlabeLes melllLus Lo decrease Lhe amounL of glucose
produced by Lhe llver and Lo lncrease Lhe body's response Lo lnsulln. ln paLlenLs wlLh
renal fallure (acuLe or chronlc), Lhe renal clearance of meLformln ls decreased, and
Lhere ls an assoclaLed rlsk of lacLlc acldosls, whlch has a morLallLy raLe of up Lo
30.
1
Some paLlenLs who recelve lnLravenous conLrasL may experlence a
deLerloraLlon of renal funcLlon (conLrasL-lnduced nephropaLhy). AlLhough Lhe polnLs
ln Lhls arLlcle dlscuss Lhe use of lnLravenous conLrasL, Lhe same prlnclples apply Lo
lnLra-arLerlal conLrasL.
Use of metform|n |s not a contra|nd|cat|on to |ntravenous contrast adm|n|strat|on
MeLformln ln lsolaLlon ls noL consldered a rlsk facLor for conLrasL-lnduced
nephropaLhy,
2
buL parLlcular aLLenLlon musL be pald Lo paLlenLs Laklng meLformln
who are scheduled Lo undergo conLrasL-enhanced examlnaLlon (e.g., enhanced
compuLed Lomography [C1], anglography, venography).
3
Many physlclans are
parLlcularly cauLlous ln Lhe case of elderly paLlenLs aged greaLer Lhan 80 years.
Ior most pat|ents, metform|n shou|d be stopped at the t|me of contrast
adm|n|strat|on
1here ls some conLroversy abouL when Lo sLop and resLarL meLformln for paLlenLs
scheduled Lo undergo lnLravenous conLrasL-enhanced examlnaLlons.
4
1he guldellnes
from Lhe Canadlan AssoclaLlon of 8adlologlsLs
2
sLaLe LhaL paLlenLs Laklng meLformln
who have an esLlmaLed glomerular fllLraLlon raLe (eCl8) of less Lhan 60 mL/mln
should sLop Laklng meLformln aL Lhe Llme of conLrasL admlnlsLraLlon. 1he Luropean
SocleLy of urogenlLal 8adlology advocaLes sLopplng meLformln 48 hours before C1
for paLlenLs wlLh an eCl8 of less Lhan 43 mL/mln.
3

kestart|ng metform|n depends on rena| funct|on and the vo|ume of contrast used
Culdellnes from Lhe Canadlan AssoclaLlon of 8adlologlsLs
2
sLaLe LhaL paLlenLs Laklng
meLformln who have an eCl8 of less Lhan 60 mL/mln should resLarL Lhe drug no
sooner Lhan 48 hours afLer conLrasL admlnlsLraLlon and only lf renal funcLlon
remalns sLable (< 23 lncrease ln creaLlnlne above basellne). aLlenLs wlLh an eCl8
above 60 mL/mln who recelve a larger amounL of lnLravenous conLrasL (> 100 mL,
e.g., C1 of Lhe abdomen or pelvls, C1 anglography of Lhe aorLa or lower exLremlLles)
should resLarL meLformln no earller Lhan 48 hours afLer Lhe procedure.
3

Ior sma|| vo|umes of contrast, pat|ents w|th norma| rena| funct|on tak|ng
metform|n may not requ|re any changes |n care
lf paLlenLs wlLh normal renal funcLlon who are Laklng meLformln recelve less Lhan
100 mL of lnLravenous conLrasL (e.g., enhanced C1 of Lhe braln), sLopplng meLformln
and/or rechecklng creaLlnlne levels 48 hours afLer Lhe procedure may be
unnecessary, because Lhe rlsk of conLrasL-lnduced nephropaLhy ln paLlenLs wlLh
normal renal funcLlon ls very low.
3


rof : Why are Lhese rlsks dlfferenL for males and females?
ulfferenL body Llssues have dlfferenL senslLlvlLy Lo radlaLlon. Skln and bone are noL
very senslLlve, buL breasL Llssue, bone marrow, and Lhe llnlng of Lhe sLomach and
lnLesLlne are senslLlve Lo Lhe effecLs of lonlslng radlaLlon. Cn average, females are
more senslLlve Lo Lhe effecLs of lonlslng radlaLlon Lhan males.

Why are Lhese rlsks dlfferenL for chlldren?

1he prlnclpal rlsk for chlldren exposed Lo x-rays ls LhaL aL Lhe Llme of exposure, Lhelr
growLh means more cells are dlvldlng, provldlng a greaLer rlsk of radlaLlon dlsrupLlng
cell developmenL. Chlldren also have a longer llfe expecLancy, glvlng a longer Llme
for Lhe effecLs of any radlaLlon damage, lf presenL, Lo have an effecL on long-Lerm
healLh.


28) Cn 18
uear ?ln llng,

M. Luberculosls dlvldes every 13-20 hours, whlch ls exLremely slow compared Lo
oLher bacLerla, whlch Lend Lo have dlvlslon Llmes measured ln mlnuLes (Lscherlchla
coll can dlvlde roughly every 20 mlnuLes). lL ls a small baclllus LhaL can wlLhsLand
weak dlslnfecLanLs and can survlve ln a dry sLaLe for weeks. lLs unusual cell wall, rlch
ln llplds (e.g., mycollc acld), ls llkely responslble for Lhls reslsLance and ls a key
vlrulence facLor. When ln Lhe lungs, M. Luberculosls ls Laken up by alveolar
macrophages, buL Lhey are unable Lo dlgesL Lhe bacLerlum. lLs cell wall prevenLs Lhe
fuslon of Lhe phagosome wlLh a lysosome. SmarL rlghL! 1haL's why glanL cells and
granulomas form Lo conLaln lL.

Al8 dlrecL smears and culLurlng meLhod ls Lhe sLandard way of screenlng 18. ulrecL
smears ofLen fall when Lhe bacLerlal load ls low whlle culLure wlll plck lL up as lL
allows Lhe bacLerla Lo mulLlply for ldenLlflcaLlon.
MosL common medla(egg-based) used ln Malaysla ls Lhe LowensLeln-!ensen medla
(used before) and now Lhe CCAWA (replaclng L! medla)

M. Luberculosls ls grown on a selecLlve medlum known as LowensLeln-!ensen
medlum, whlch has LradlLlonally been used for Lhls purpose. Powever, Lhls meLhod
ls qulLe slow, as Lhls organlsm requlres 6-8 weeks Lo grow, whlch delays reporLlng of
resulLs. LwensLeln-!ensen (L!) medlum ls mosL wldely used for Luberculosls culLure.
L! medlum conLalnlng glycerol favours Lhe growLh of M. Luberculosls. A fasLer resulL
can now be obLalned uslng Mlddlebrook medlum or 8AC1LC.

8u1 WhaL ls 8AC1LC?

lL ls a broLh-based culLure sysLem deslgned Lo lmprove Lhe speed and senslLlvlLy of
deLecLlon. 1he 8AC1LC sysLem ls based upon Mlddlebrook 7P12 medlum conLalnlng
14C labelled palmlLlc acld wlLh a mlxLure of anLlbloLlcs (An1A) Lo suppress oLher
bacLerlal growLh. 1he addlLlon of nA (p-nlLro-alpha-aceLylamlno-beLa-
hydroxyproplophenone) ln Lhe medlum suppresses growLh of oLher M. Luberculosls
complex organlsms such as M. bovls buL does noL dlfferenLlaLe oLher
nonLuberculous mycobacLerla from M. Luberculosls.

8acLerlal growLh ls lndlcaLed by Lhe deLecLlon of 14C released by M. Luberculosls as
lL meLabollzes Lhe palmlLlc acld. ln Al8 smear-poslLlve speclmens, Lhe 8AC1LC
sysLem can deLecL M. Luberculosls ln approxlmaLely elghL days compared Lo
approxlmaLely 14 days for smear-negaLlve, culLure-poslLlve speclmens. Powever,
Lhe hlgh cosL of Lhe equlpmenL and Lhe need for radloacLlve maLerlal LhaL requlres
dlsposal exclude lLs use ln mosL 18 endemlc communlLles.
CrowLh deLecLed by Lhe lndlcaLor sysLem ln drug-conLalnlng broLh ls lnLerpreLed as
reslsLance Lo Lhe drug. 1he Lurnaround Llme for reslsLance LesLlng ls 10 days.

1hls meLhod ls very successful and rellable and LhaL conflrmaLory resulLs for M.
Luberculosls can be obLalned wlLhln Lwo weeks. Powever, Lhe 8AC1LC machlne ls
very expenslve Lo purchase and Lo operaLe.


WhaL ls CCAWA MLuluM?

lL ls an egg based medlum Lo culLure M. Luberculosls. CCAWA MLuluM
ls cheaper Lhan LwensLeln-!ensen because lL ls made wlLhouL asparaglne. L! need a
loL of lngredlenLs compared Lo Cgawa. 1hls ls why L! medla cosLs more. 1hls meLhod
ls much cheaper Lhan 8acLec.

1he ldeal medlum for lsolaLlon of Lubercle bacllll should (a) be economlcal and
slmple Lo prepare from readlly avallable lngredlenLs, (b) lnhlblL Lhe growLh of
conLamlnanLs, (c) supporL luxurlanL growLh of small numbers of bacllll and (d)
permlL prellmlnary dlfferenLlaLlon of lsolaLes on Lhe basls of colony morphology. 1he
Cgawa med|a |s better than LI |n terms of cost, growth rate and contam|nat|on
rate.

8U1 Speed |s k|ng w|th A prem|um to pay
1he mean detect|on t|me for M. tubercu|os|s comp|ex was 1S days w|th the
8AC1LC method, and 26 days w|th the Cgawa method.
29) CN S1kCkL
uear ?ln llng,
Why ls lL LhaL we refer Lo 7Lh and 12Lh Cns as elLher uMn or LMn buL noL when we
speak of Lhe oLher Cns?

AlmosL all of Lhe cranlal nerves recelve bllaLeral lnnervaLlon from Lhe flbers of Lhe
pyramldal LracL. 1hls means LhaL boLh Lhe lefL and rlghL members of a palr of cranlal
nerves are lnnervaLed by Lhe moLor sLrlp areas of boLh Lhe lefL and rlghL
hemlspheres. 1hls redundancy ls a safeLy mechanlsm. lf Lhere ls a unllaLeral leslon
on Lhe pyramldal LracL, boLh sldes of body areas connecLed Lo cranlal nerves wlll
conLlnue Lo recelve moLor messages from Lhe corLex. 1he message for movemenL
may noL be qulLe as sLrong as lL was prevlously buL paralysls wlll noL occur.

1he Lwo excepLlons Lo Lhls paLLern are Lhe porLlon of 12Lh Cn LhaL provldes
lnnervaLlon for Longue proLruslon and Lhe parL of 7Lh Cn LhaL lnnervaLes Lhe
muscles of Lhe lower face. 1hese only recelve conLralaLeral lnnervaLlon from Lhe
pyramldal LracL. 1hls means LhaL Lhey geL lnformaLlon only from flbers on Lhe
opposlLe slde of Lhe braln. 1herefore, a unllaLeral upper moLor neuron leslon could
cause a unllaLeral faclal droop or problems wlLh Longue proLruslon on Lhe opposlLe
slde of Lhe body. lor example, a leslon on Lhe lefL pyramldal LracL flbers may cause
Lhe rlghL slde of Lhe lower face Lo droop (8 uMn 7Lh Cn palsy) and lead Lo dlfflculLy
ln proLrudlng Lhe rlghL slde of Lhe Longue (8 uMn 12Lh Cn palsy).


8uL even Lhe 12Lh ofLen has a small supply from Lhe oLher slde, hence Lhe qulck
recovery of Lhe devlaLlon ln uMn leslons. Whlle mosL people have bllaLeral
lnnervaLlon of Lhe 12Lh Cn, Lhls ls nC1 seen ln oLhers. WhaLs Lhe boLLom llne Lhen...
conLralaLeral lnnervaLlon ls domlnanL whlle Lhere ls bllaLeral lnnervaLlon ln some.
Pence ln a uMn leslon, Lhe Longue devlaLlon ls seen early and Lhen may lmprove
wlLh Llme, ln Lhose wlLh very slgnlflcanL bllaLeral lnnervaLlon, ln a uMn leslon Lhe
devlaLlon ls mlnlmal or noL seen aL all.

1he oLher cranlal nerves lnvolved ln speech and swallowlng would conLlnue Lo
funcLlon almosL normally as boLh members of each palr of nuclel sLlll recelves
messages from Lhe moLor sLrlp.

8ecause mosL cranlal nerves recelve bllaLeral lnnervaLlon, leslons of Lhe upper
moLor neurons of Lhe pyramldal LracL musL be bllaLeral ln order Lo cause a serlous
speech problem. Pence seudo 8ulbar and 8ulbar palsles.

Cn Lhe oLher hand, unllaLeral leslons of Lhe lower moLor neurons may cause
paralysls. 1hls occurs because Lhe lower moLor neurons are Lhe flnal common
paLhway for neural messages Lravellng Lo Lhe muscles of Lhe body. AL Lhe level of
Lhe lower moLor neurons, Lhere ls no alLernaLlve rouLe whlch wlll allow messages
from Lhe braln Lo reach Lhe perlphery. Muscles on Lhe same slde of Lhe body as Lhe
leslon wlll be affecLed. When Lhere ls eg a 3rd Cn palsy lL ls undersLood Lo be a LMn
leslon.



ou have reached the MIDCIN1 of th|s book.
Why I am CRANKY when Teaching my medical students!

l belleve LhaL Lhls ls because my body and mlnd ls lrreverslbly damaged/dlsLorLed by
years of medlcal school Lralnlng. l belleve LhaL Lhe 8raln surgery LhaL was done on
my braln made lL non compllanL Lo any sLudenLs noL conformlng Lo Lhe unl culLure of
lasL cenLury.
LeL me recall some hlghllghLs...
ln year1, we had a rofessor of AnaLomy who was so flerce LhaL grown men wlll cry
when she walked ln. 1he 'name who musL noL be menLloned' wlll walk around wlLh a
forcep ln Lhe dlssecLlon hall, randomly plck up a sLrucLure and 8CCM "Why ls Lhls?
Crlgln? lnserLlon? luncLlon??"
MosL of us were menLally casLraLed by Lhe Llme we flnlshed anaLomy and any
survlvors would have been polsoned by Lhe all overwhelmlng lormalln anyway! 8y
Lhe way, we dlssecLed wlLh our 8A8L PAnuS! 1haL's Lhe 20Lh cenLury for you. 1hank
goodness ur 1an 1oo Moh my year one buddy was a surglcal genlus who falLhfully
dlssecLed every superflclal nerve and Lendon whlle l navlgaLed from Lhe dlssecLlon
manual. When rof "Who musL noL be named" walked near, l leap lnLo llfe and
burled my hands ln Lhe leaLhery body.
We had rof 8aman ln hyslology who recurrenLly LhreaLened Lo hang us on Lhe Lree
whenever we flunked hls MCCs. Many of us would have dled many Llmes! 8uL Lhls
was one greaL Leacher who LaughL us much3 hyslology. 1he rof 8aman physlology
qulz now held annually ls ln hls memory.
And rof Loke of 8lochemlsLry made us feel so so small when he wroLe on Lhe
8lackboard wlLh 8C1P PAnuS slmulLaneously and efforLlessly Lhe compllcaLed
formulas of 8lochemlsLry llke you and l wrlLlng a nursery rhyme. Ck we felL llke
CreLlns by 1sL year! And l haLed Lhe unA sLrucLures LhaL Lhey LaughL.... why oh why
dld Lhey LorLure us wlLh LhaL!
And each sub[ecL had lLs own Lssay quesLlon examlnaLlon, MCC and pracLlcal
exam!!! 9 exam sesslons!!
8y some unknown mlracle we survlved year1 only Lo plunge lnLo Lhe arms of rof
Chal ln year2, hls Mlcroblology ln no way made hls hands mlcro.. for he wlll wlLhouL
heslLaLlon plnch anyone of us squarely ln Lhe belly when we do noL know Lhe SLalns,
CulLures and lmmunology of all hls unseen frlends. CuCP3! 81W Lhls was before Lhe
days of measuremenL of abdomlnal skln fold Lhlckness, had Lhe good rofessor
known Lhen, he would have collecLed enough daLa for hls hu.
rof raLhap of aLhology was Lhe genLleman of genLlemen, ever so calm, cool and
collecLed. Ck he was probably Lhe only man ln medlcal school who dld noL scold us,
8LLSS Lhe man.
ln araslLology, we sLlrred shlL ln saLuraLed sallne llke how your mummy would beaL
flour Lo make a cake, Lhe dlfference belng LhaL Lhe cake wlll smell dellclous whlle we
smell ln a manner LhaL gave reason for Lhe medlcal faculLy Lo be placed ln Lhe far
flung corner of Lhe campus. lL also explalns why Lhe beauLlful glrls from Lhe ArLs
faculLy sLayed puL ln Lhelr dlagonally placed faculLy.
Some of Lhose paraslLes may well have enLered our bralns Loo for we also slepL,
sLudled and aLe ln Lhe very same 'mulLl-dlsclpllne' laboraLorles'.
harmacology was abouL harmacoklneLlcs and hamacodynamlcs, lL made our
mlnds as conLorLed as Lhe double hellx. 1he poor caLs from Lhe Cllnlcal PosLel
lnvolunLarlly gave Lhelr llves for us Lo undersLand "1herapeuLlc lndex" and "LeLhal
doses"! Alyo, l sLlll shudder when l Lhlnk of Lhe poor fellne on LhaL heaLed Lable
hooked up on monlLors. We waLched ln horror as adrenallne was slowly lnfused lnLo
lLs velns and Lhe cardlac monlLor wenL dlL, dlL, dlL Lhen a hundred Llmes fasLer when
a Lechnlclan whlpped ouL a scalpel and opened up lLs chesL ln llke 3 secs exposlng a
flbrlllaLlng caL hearL. Ck anoLher sychologlcal scar lasered lnLo my braln!
Whoople! We flnlshed Lhe 8aslc sclences and walked proudly lnLo unlverslLy
PosplLal wlLh our 8rand new sLeLhoscopes and Lendon hammers. 3 years of
Clerkshlp followed 8u1 walL!! Clerks slL down and work, we S1CCu for 3 years! now
l undersLand why my knees hurL whenever l sLand for long now.
SLudenLs nowadays do nC1 undersLand Lhe meanlng of Lhe word "1L88C8", nope
you do noL unLll you are selecLed by Lhe drawlng of sLraws Lo presenL Lhe Long Case
Lo rof uanara[. now LhaL's pure Lerror. 1he good rofessor's expecLaLlon of PlsLory
ls so deLalled LhaL War and eace would look llke a shorL sLory ln comparlson. Pls
expecLaLlon of our physlcal examlnaLlon ls so compleLe LhaL 1PL Ln1l8L 1ally's LhaL
you all use Loday wlll seem lnadequaLe ln hls eyes. 1PL A1lLn1 lS ALWA?S
CCMLL1LL? LxAMlnLu, a concepL Loday's sLudenLs slmply fall Lo grasp Lo my
eLernal lrrlLaLlon. And Lhe Lendon hammer wlll whlsk abouL freely llke a conducLor's
baLon, occaslonally landlng on our Lhlghs as a reward for a really lgnoranL answer!
My sLomach probably developed gasLrlLls from Lhe ward rounds and cllnlcs of rof
llorence Wang, lL was lnLermlnable as she paLlenLly spoke Lo LvL8? paLlenL ln Lhe
ward and cllnlc, examlned every paLlenL personally nC MA11L8 who dld so
beforehand and Lhen grllled Lhe Pouseman and sLudenLs ln Lhe enLourage. She
LaughL me LhaL whlle lL ls lmporLanL Lo LreaL Lhe paLlenL's physlcal lllness, lL ls even
more lmporLanL Lo LreaL Lhe paLlenL's mlnd and show hlm/her LhaL you care. 1reaL
Lhe Puman belng, noL [usL Lhe dlsease.
ln surgery, Lhe Leachers consLanLly remlnded me LhaL my knowledge of anaLomy ls
as low as "Lhe skln of a plg's belly"... aka nLx1 1C nu1Pln! Ck LhaLs one reason l
chose lnLernal Medlclne.
ln sychlaLry we had a lecLurer who wore a 8LuL shlrL for all Lhe years LhaL we were
aL unl! And rof ueva wlll ask and ask and ask "WP?". aLlenL cannoL sleep slr.......
WP??, 8ecause he feel sLressed slr..... WP??, because hls buslness has problems
slr.... WP??..... eL lnflnlLum.
And ln aedlaLrlcs rof Lam wlll llLerally !uM up and uown on Lhe spoL whenever
we do someLhlng or say someLhlng "S1ulu"!
"1hls chlld was apparenLly well unLll.".
"!usL because Lhe *+ PuLchlson says LhaL you sLarL Lhe presenLaLlon LhaL way,
you mlndlessly can CnL? do lL LhaL way!!!!" !uM3!
And rof SlnnaLhuray of CC wlll llLerally S1Anu aL Lhe enLrance Lo caLch all Lhe
sLudenLs who came laLe! Palf my sLudenLs Loday wlll be queulng aL Lhe uean's offlce
Loday Lo explaln lf we follow Lhe same meLhods! now we have a sweeL counsellor Lo
slowly Lalk sense lnLo Lhem.
So much for why your braln damaged LuLor Loday l8LAkS ouL when Lhe sLudenLs
come laLe, noL know Lhelr baslc sclences, or do a physlcal examlnaLlon so AnALMlC
LhaL ernlclous Anaemla seems more plnk! lL ls really because of Lhe sofLware fed
lnLo me LhaL refuses Lo move lnLo Lhe 21sL cenLury.

30) Cn kheumato|d Iactor
uear ?ln Llng,
ln 39 days you wlll slL for your exams. l wlll expedlLe all LhaL l can do Lo help you
revlse. l wlll even answer my own quesLlons!

8l ls a very common LesL.

8heumaLold facLor ls an lmmunoglobulln whlch can blnd Lo oLher anLlbodles.
8heumaLold facLor ls found ln about 1-2 of hea|thy peop|e. 1he lncldence of
rheumato|d factor |ncreases w|th age and abouL 20 of people over 63 years old
have an elevaLed rheumaLold facLor. 1haL ls why lL ls so commonly seen as poslLlve
ln screenlng blood LesLs ln Lhe elderly.

Plgh LlLers of rheumaLold facLor are assoclaLed wlLh more severe rheumaLold
arLhrlLls. 1he facLor also has been assoclaLed wlLh a hlgher Lendency Lo develop Lhe
non-[olnL compllcaLlons of Lhe dlsease such as rheumaLold nodules and rheumaLold
lung dlsease.

8heumaLold facLor ls presenL ln abouL 80 of adulLs (buL a much lower proporLlon
of chlldren) wlLh rheumaLold arLhrlLls. lL ls also presenL ln paLlenLs wlLh oLher
connecLlve Llssue dlseases such as sysLemlc lupus eryLhemaLosus and S[gren's
syndrome, and some wlLh lnfecLlons dlseases lncludlng lnfecLlous hepaLlLls.

1esL: Cne meLhod mlxes Lhe paLlenL's blood wlLh Llny laLex beads covered wlLh
human anLlbodles (lgC). 1he laLex beads clump or aggluLlnaLe lf rheumaLold facLor
(lgM 8l) ls presenL.

A rheumaLold facLor LlLer more than 1:80 ls lndlcaLlve of rheumaLold arLhrlLls buL
may also occur ln oLher condlLlons.
Ia|se pos|t|ve resu|ts can occur when the b|ood |s h|gh |n fats.

A negat|ve test resu|t for rheumato|d factor does not exc|ude the d|agnos|s of
rheumato|d arthr|t|s.

1he presence of Lhls marker ls noL, however, needed Lo make Lhe dlagnosls of
rheumaLold arLhrlLls. ln facL 13-23 percenL of all paLlenLs wlLh rheumaLold arLhrlLls
do noL have rheumaLold facLor ln Lhelr serum. 1here ls no concluslve laboraLory LesL
whlch conflrms Lhe dlagnosls of rheumaLold arLhrlLls.

aLlenLs are ofLen Llmes fearful, when Lhelr docLor Lells Lhem LhaL a rheumaLold
facLor (8l) was found on rouLlne laboraLory LesLlng. lmmedlaLely, Lhey assume LhaL
Lhey have developed rheumaLold arLhrlLls (8A). 1hls ls slmply noL Lhe case.

Ant|-c|tru|||nated prote|n ant|body (ACA) |s a better too| for |dent|fy|ng
rheumato|d arthr|t|s than rheumato|d factor |eve|s

now remember Lhe old 8rlLlsh car MC and you wlll remember lLs lgM agalnsL lgC!!!

ur Pu : WhaL ls seronegaLlve' sLand for ? WhaL ls seronegaLlve arLhrlLls ?
(lease Lake noLe, rheumaLold arLhrlLls (8A) ls noL lncluded as seronegaLlve arLhrlLls
even lL can be seronegaLlve.).

8heumaLold facLor (8l) & AnLlbodles agalnsL Cycllc ClLrulllnaLed epLldes (ACC)
have less senslLlvlLy ln Lhe dlagnosls of early dlsease phase of 8A."

AL presenL, 8A ls dlagnosed based on fulflllmenL of Lhe classlflcaLlon crlLerla seL by
Lhe Amerlcan College of 8heumaLology (AC8), whlch have recenLly been revlsed by a
[olnL AC8 and LuLA8 commlLLee. ln Lhe revlsed crlLerla, ob[ecLlve serologlcal LesLlng
for Lhe presence of 2 8A dlsease markers, rheumaLold facLor (8l) and anLlbodles
dlrecLed agalnsL cycllc clLrulllnaLed pepLldes (ACC), ls lncluded as an lmporLanL
crlLerlum.

Powever, accordlng Lo recenL meLa-analyses, approxlmaLely one-Lhlrd of esLabllshed
8A paLlenLs are seronegaLlve for Lhese 2 dlagnosLlcally applled dlsease markers.
Moreover, Lhe senslLlvlLles of boLh markers for 8A are reporLed Lo be even lower ln
Lhe dlagnosLlcally lmporLanL early dlsease phase.

LxLra-arLlcular/sysLemlc manlfesLaLlon can appear ln early sLage of 8A"

LxLra-arLlcular manlfesLaLlon usually develop ln paLlenLs wlLh long Lerm and severe
8A, however, ln some cases sysLemlc manlfesLaLlon such as lnLersLlLlal pulmonary
dlseases, pleurlLls or perlcardlLls can appear ln early" sLages of Lhe dlsease.

8A also can has poslLlve AnA/anLl-double-sLranded (anLl-ds) unA".

Ant|nuc|ear ant|bod|es (ANA) and ant|-doub|e-stranded (ant|-ds) DNA ant|bod|es
may be present |n pat|ent w|th kA, a|though, the phys|c|ans have to be aware that
treat|ng kA w|th ant|-1NI monoc|ona| ant|bod|es |nf||x|mab can |ncrease serum
|eve|s of ANA and ant|-ds DNA.

Ck more spec|f|c than LSk |n measure d|sease act|v|ty"

1yplcally, acuLe phase reacLanLs such as sedlmenLaLlon raLe (LS8) and reacLlve C
proLeln (C8) are used Lo measure Lhe dlsease acLlvlLy. 1hese are markers of Lhe
sysLemlc acuLe lnflammaLory response, however, C8 levels are more speclflc for 8A
compared wlLh Lhe eryLhrocyLe sedlmenLaLlon raLe (LS8) levels, slnce C8 are more
correlaLed wlLh hlgher levels of pro lnflammaLory cyLoklnes, such as lnLerleukln
(lL)6 and 1nl- and relaLed wlLh radlologlcal progresslon.

31) on WA1Lk AND LLLC1kCL1LS
uear ?ln Llng,

Lvery year l ask Lhe sLudenLs as Lo how much urlne Lhey produce ln a day.... and
every year l am AMAZLu LhaL noL a few have nC CLuL!

?ou know of course LhaL WaLer and na balance are closely lnLerdependenL.

1oLal body waLer (18W) ls abouL 60 of body welghL (ranglng from abouL 30 ln
obese people Lo 70 ln lean people, l keep Lelllng aunLle LhaL lL ls ok for me Lo run ln
Lhe raln Lo Lhe car as l am 70 waLer!).

A|most 2]3 of 18W |s |n the |ntrace||u|ar compartment (|ntrace||u|ar f|u|d), the
other 1]3 |s extrace||u|ar (extrace||u|ar f|u|d). Norma||y, about 2S of the LCI |s |n
the |ntravascu|ar compartment, the other 7S |s |nterst|t|a| f|u|d.

1oLal body waLer = 70 kg 0.60 = 42 L.

1he ma[or lnLracellular caLlon ls k, wlLh an average concenLraLlon of 140 mLq/L. (1o
remember Lhlnk of na concenLraLlon ln blood). 1he exLracellular k concenLraLlon ls
CnL? 3.3 Lo 3 mLq/L. uo reallse Lhe PuCL CradlenL!

1he ma[or exLracellular caLlon ls na, wlLh an average concenLraLlon of 140 mLq/L
and an lnLracellular na concenLraLlon of 12 mLq/L. 1he na-k exchange pump ls
super duper efflclenL Lo malnLaln Lhls gradlenL.

CsmoLlc forces: 1he concenLraLlon of comblned soluLes ln waLer ls osmolarlLy (lLs ln
slmple words Lhe amounL of soluLe per L of soluLlon la), whlch, ln body flulds, ls
slmllar Lo osmolallLy (amounL of soluLe per kg of soluLlon). Words words words... a
llLre of fluld ls abouL 1 kg ma!

Pence, lasma osmolallLy can be esLlmaLed accordlng Lo Lhe formula

|asma osmo|a||ty (mCsm]kg) = Na + G|ucose + Urea

where serum na ls expressed ln mLq/L and glucose and 8un are expressed ln
mg/dL. CLu unl1S. 1hese are Lhe 8lC 8C?s ma.

Whose Lhe number 1 badmlnLon player ln Lhe world? Chong Wel, everyone knows
rlghL! Whose no 2? Lln uan rlghL! now whose no 3?? Lrrrr Lrrrr. Cnly Lhe blg boys
are 8lC, Lhe resL cannoL remember! Same ln 8lood! 8emember Lhe 8lC 8C?s! ?our
blood when you blLe your Longue ls SAL1?! 1haLs Lhe Chong Wel! lf you are dlabeLlc
lL may be sweeL lorr. 1haLs Lln uan and of course as 8enal fallure comes, urea ls a
8lC player now.

Csmo|a||ty of body f|u|ds |s norma||y between 27S and 290 mCsm]kg.

na ls Lhe ma[or deLermlnanL of serum osmolallLy.

An osmo|ar gap |s present when measured osmo|a||ty exceeds est|mated
osmo|a||ty by z 10 mCsm]kg. When th|s happens, there |s a DAkk nCkSL!!
Someone has crept |n and upset the kANkING CkDLk! WnC IS 1nA1 you must ask!

lL ls caused by unmeasured osmoLlcally acLlve subsLances presenL ln Lhe plasma. 1he
mosL common are alcohols (ethano|, methano|, |sopropano|, ethy|ene g|yco|),
mann|to| and g|yc|ne.

lrom Lhe formula you can see how urea affecLs Lhe osmolallLy ln Lhe LS8l paLlenL.

WaLer crosses cell membranes freely from areas of low soluLe concenLraLlon Lo
areas of hlgh soluLe concenLraLlon. 1hus, osmolallLy Lends Lo equallze across Lhe
varlous body fluld comparLmenLs, resulLlng prlmarlly from movemenL of waLer, noL
soluLes. noLe LhaL SoluLes such as urea LhaL freely dlffuse across cell membranes
have llLLle or no effecL on waLer shlfLs (llLLle or no osmoLlc acLlvlLy), whereas soluLes
LhaL are resLrlcLed prlmarlly Lo one fluld comparLmenL, such as na and k, have Lhe
greaLesL osmoLlc acLlvlLy.

WaLer lnLake and excreLlon: 1he average dally fluld lnLake ls abouL 2.3 L. ( noLe Lhe
lvu reglmes we use when a paLlenL ls "nll by mouLh! Pow much fluld do we glve??)

ln Lhe normal resLlng sLaLe, lnpuL of waLer Lhrough lngesLed flulds ls approxlmaLely
1200 ml/day, from lngesLed foods 1000 ml/day and from meLabollsm 300 ml/day,
LoLallng 2300cc/day. noLe Lhe maglc number!

1he amounL needed Lo replace losses from Lhe urlne and oLher sources ls abouL 1 Lo
1.3 L/day ln healLhy adulLs. (MosL of you are smarL Lo carry a 1000cc boLLle!)
Powever, on a shorL-Lerm basls, an average young adulL wlLh normal kldney
funcLlon may survlve on as llLLle as 200 mL of waLer each day Lo excreLe Lhe
nlLrogenous and oLher wasLes generaLed by cellular meLabollsm. 1he urlne wlll be
very concenLraLed! More ls needed ln people wlLh any loss of renal concenLraLlng
capaclLy.

lf we are Lo use urlne ouLpuL as a means of [udglng adequaLe hydraLlon sLaLus, Lhls
flrsLly assumes LhaL Lhe renal funcLlon ls nC8MAL. If we see at |east 1-1.Scc of ur|ne
output a m|nute, th|s |s reassur|ng of adequate prov|s|on of f|u|ds. At 1cc a m|nute,
we expect 60cc an hour and about 1S00cc per day. 1h|s |s about the average ur|ne
output for an adu|t.

When we do noL drlnk or ls noL on lvu, Lhe kldneys wlll concenLraLe our urlne as you
wlll noLlce ln Lhe urlne LhaL you pass on waklng up, lLs concenLraLed afLer noL
drlnklng for 7-8 hours of sleep.

8enal concenLraLlng capaclLy ls losL ln
-1he elderly
-aLlenLs wlLh dlabeLes lnslpldus, cerLaln renal dlsorders, hypercalcemla, severe salL
resLrlcLlon, chronlc overhydraLlon, or hyperkalemla
-eople who lngesL eLhanol, phenyLoln, llLhlum, or amphoLerlcln 8
-eople wlLh osmoLlc dluresls (eg, due Lo hlgh-proLeln dleLs or hyperglycemla)

CLher obllgaLory waLer losses are mosLly lnsenslble losses from Lhe lungs (abouL
300cc) and skln (dependlng on amblenL LemperaLure and humldlLy, lL varles from
300 onwards), averaglng abouL 630 Lo 830 mL/day ln a 70-kg adulL. SweaL losses can
be slgnlflcanL durlng envlronmenLal heaL exposure (llke ln Lhe lasL few days, noLlce
my waLer boLLle empLles fasL Lo replace my sweaL ln Lhe wards) or excesslve
exerclse. WlLh fever, anoLher 30 Lo 73 mL/day may be losL for each degree C of
LemperaLure elevaLlon above normal.

Assum|ng a |oss of about 800cc from breath|ng and sweat|ng LUS whatever ||tt|e
ur|ne |s passed by the LSkI pat|ent on nD, that |s h|s a||owed water |ntake per day.

Cl losses are usually negllglble, excepL when vomlLlng, dlarrhoea, or boLh occur.

WaLer lnLake ls regulaLed by LhlrsL. 1hlrsL ls Lrlggered by recepLors ln Lhe
anLerolaLeral hypoLhalamus LhaL respond Lo lncreased serum osmolallLy (as llLLle as
2) or decreased body fluld volume. 8arely hypoLhalamlc dysfuncLlon decreases Lhe
capaclLy for LhlrsL.
WaLer excreLlon by Lhe kldneys ls regulaLed prlmarlly by AuP (vasopressln). AuP ls
released by Lhe posLerlor plLulLary and resulLs ln lncreased waLer reabsorpLlon ln Lhe
dlsLal nephron. ADn re|ease |s st|mu|ated by any of the fo||ow|ng:
Increased serum osmo|a||ty
Decreased b|ood vo|ume
Decreased 8
Stress!! 8emember Lhls! A paLlenL posL surgery, sepLlc or ln my Long Case class or
worse 8LuSluL Class wlll have lncreased AuP ouLpuL. (l cannoL undersLand why
some sLudenLs keep golng Lo Lhe LolleL, beLLer check your renal funcLlon!)

AuP release may be lmpalred by cerLaln subsLances (eg, eLhanol, phenyLoln) and
cenLral dlabeLes lnslpldus

WaLer lnLake decreases serum osmolallLy. Low serum osmolallLy lnhlblLs AuP
secreLlon, allowlng Lhe kldneys Lo produce dlluLe urlne.



32) CN 8ILIkU8IN ML1A8CLISM
uear ?ln Llng,

when we see a paLlenL wlLh [aundlce, Lhe physlology of 8lllrubln meLabollsm musL
be aL Lhe back of our mlnds ln order Lo Lhlnk of dlfferenLlal dlagnosls. 1hls separaLes
medlclne from quackery. noL all [aundlce ls due Lo llver dlseases and llver dlseases
are noL always accompanled wlLh [aundlce!!

8lllrubln, a physlologlcal producL of 88C, ls meLabollzed ln Lhe llver and excreLed lnLo
blle ducLs, an appearance of [aundlce means LhaL Lhere ls a breakdown of balance of
blllrubln meLabollsm and Lhe paLlenL may have a problem ln Lhe llver, or 88C
producLlon and desLrucLlon, or excreLlon of blllrubln. eg hemolyLlc dlseases: Always
keep lL ln mlnd when managlng a paLlenL wlLh [aundlce.

8lllrubln ls an end producL of heme meLabollsm, comlng malnly, 70 80 , from
hemoglobln of senescenL red blood cells, lL spllLs Lo heme and globln, Lhen furLher
spllL Lo lron and blllverdln, and Lhe blllverdln converLs Lo blllrubln.

8lllrubln comblnes wlLh albumln ln Lhe blood sLream, only separaLed [usL before
belng upLaken lnLo llver cells. 1he blllrubln ln Lhe hepaLocyLes con[ugaLes wlLh
glucuronlc acld Lo become con[ugaLed blllrubln, whlch ls excreLed Lo Lhe blllary LracL
and lnLesLlnes and flnally excreLed.
1he blllrubln from hemoglobln ls free uncon[ugaLed blllrubln ln Lhe blood sLream
and ls noL soluble ln waLer. AfLer belng Laken lnLo hepaLocyLes, lL ls converLed Lo
soluble con[ugaLed form and excreLed lnLo blle ducLs.

1he blllrubln ls dlvlded lnLo Lwo Lypes, dlrecL reacLlng blllrubln and lndlrecL reacLlng
blllrubln, accordlng Lo lLs mode of reacLlon durlng Lhe LesL process. lL can be
recognlzed LhaL dlrecL reacLlng blllrubln ls Lhe con[ugaLed blllrubln and Lhe lndlrecL
reacLlng blllrubln as uncon[ugaLed blllrubln.

Con[ugaLed blllrubln ls absorbed ln Lhe dlsLal porLlon of Lhe lleum afLer lLs
hydrolyzed and converLed Lo u8Cblllnogen by Lhe lnLesLlnal paLhogens.
AbouL 13 20 of Lhe uroblllnogen ls reabsorbed from Lhe lnLesLlne lnLo porLal
velns and flnally 90 of Lhem reLurn Lo Lhe llver and ls re-excreLed ln Lhe blle, Lhe
enLero-hepaLlc clrculaLlon of blllrubln. 1he remalnlng 10 geLs lnLo Lhe sysLemlc
clrculaLlon and flnally excreLed ln Lhe urlne Lhrough kldney. 1hus urlne uroblllnogen
lncreases ln hemolyLlc dlsease.

Pyperblllrublnemla -- [aundlce occurs when Lhe blllrubln balance beLween
producLlon and excreLlon breaks down.

Lhe posslble causes of hyperblllrublnemla:
1. over producLlon of blllrubln from hemolysls
2. Lhe lmpalrmenL ln blllrubln upLake and con[ugaLlon ln Lhe llver,
3. lmpalred excreLlon from Lhe llver cells or Lhe llver
4. Lhe uncon[ugaLed and con[ugaLed blllrubln LhaL ls leaked lnLo Lhe blood sLream
from damaged llver cells.

Plgh-uncon[ugaLed-blllrublnemla

(1) CverproducLlon:
normal llver can handle Lhe amounL of seven Llmes of normal dally blllrubln
producLlon.
When Lhe producLlon of blllrubln ls lncreased due Lo hemolysls and and lneffecLlve
eryLhropolesls beyond Lhe ablllLy of normal llver Lo handle, Lhe serum lndlrecL
blllrubln wlll lncrease and Lhls ls prehepaLlc [aundlce. AS1, AL1 and Alk-, LhaL reflecL
Lhe damage of hepaLocyLes wlll remaln normal and predomlnanLly lndlrecL blllrubln
ls lncreased. noLe LhaL 1he con[ugaLed blllrubln may lncrease sllghLly because of Lhe
hlgh Lurnover.

(2) AbnormallLy ln upLake and con[ugaLlon:

Serum lndlrecL blllrubln may lncrease when Lhere ls problems of upLake and
con[ugaLlon ln Lhe llver cells of blllrubln. 1hls ls non-hemolyLlc uncon[ugaLed
hyperblllrublnemla.
Crlgler-na[[ar syndrome (congenlLal non-hemolyLlc [aundlce) ls caused by Lhe
deflclency of glucuronyl Lransferase. 1he sympLoms wlll appear ln Lhe lnfanL sLage,
and Lhere are Lwo Lypes, 1ype l ls more severe Lhan 1ype ll, and may lnduce
kernlcLerus.

CllberL's syndrome or ldlopaLhlc uncon[ugaLed hyperblllrublnemla ls caused by Lhe
slmllar mechanlsm as Crlgler-na[[ar syndrome, and only dlfferenL ln degree.

Plgh-con[ugaLed-blllrublnemla:

uncon[ugaLed-blllrubln con[ugaLes wlLh glucuronlc acld Lo become con[ugaLed-
blllrubln.
When LransporLaLlon of con[ugaLed-blllrubln ls lmpalred ln Lhe llver durlng Lhe
excreLlon process from llver cells or durlng passage from blle ducLules, Lhe condlLlon
ls called cholesLaLlc [aundlce.

(1) lnLrahepaLlc causes of cholesLasls:

1he [aundlce ln drug-lnduced hepaLlLls and ln pregnancy ls lnLra-hepaLlc cholesLasls.

uubln-!ohnson Syndrome and 8oLor Syndrome are congenlLal causes of lnLrahepaLlc
cholesLasls. 1he lncrease of serum blllrubln ls malnly con[ugaLed-blllrubln, and 8oLor
syndrome ls consldered as a varlanL of uubln-!ohnson syndrome. Morphologlcally,
melanln plgmenLs deposlL ln Lhe llver cells are noLed ln uubln-!ohnson syndrome
buL noL ln 8oLor Syndrome.

rlmary blllary clrrhosls shows obsLrucLlon of blllary ducLules and lnLer-lobular blle
ducLules.
rlmary/secondary scleroslng cholanglLls wlll lnduce hyper-con[ugaLed-
blllrublnemla.

ln hepaLocyLe dlseases, l.e. acuLe and chronlc llver dlseases lncludlng clrrhosls, Lhe
upLake, con[ugaLlon and excreLlon of blllrubln ln Lhe hepaLocyLes are lmpalred and
lnduce an lnLra-hepaLlc cholesLasls. 1herefore, Lhe serum blllrubln elevaLlon ls a
mlxed Lype.

(2) LxLrahepaLlc cholesLasls:

SLones, paraslLes, Lumours ln Lhe blllary LracL, blllary obsLrucLlon due Lo exLernal
compresslon from Ca ancreas wlll lnduce elevaLlon ln serum con[ugaLed-blllrubln.

no con[ugaLed blllrubln ls presenL ln normal urlne. Cnly con[ugaLed-blllrubln wlll
pass Lhrough renal glomerull. Serum level of blllrubln does noL parallel Lo Lhe
amounL of urlnary blllrubln.

uroblllnogen- only a small parL of uroblllnogen absorbed from Lhe lnLesLlnal LracL ls
excreLed ouL of Lhe body Lhrough Lhe kldney, and mosL of Lhe uroblllnogen reLurn Lo
Lhe llver and are re-excreLed Lo Lhe lnLesLlnal LracL.
1he amounL of urlnary uroblllnogen ls affecLed by Lhe amounL of con[ugaLed-
blllrubln ln Lhe blllary ducL and also lnLesLlnal paLhogens LhaL converL blllrubln Lo
uroblllnogen.
uroblllnogen ls a colourless producL of blllrubln reducLlon. 1hls consLlLuLes Lhe
"enLerohepaLlc uroblllnogen cycle".
lncreased amounLs of blllrubln are formed ln haemolysls, whlch generaLes lncreased
uroblllnogen ln Lhe guL.
ln llver dlsease (such as hepaLlLls), Lhe lnLrahepaLlc uroblllnogen cycle ls lnhlblLed
also lncreaslng uroblllnogen levels.

uroblllnogen ls converLed Lo Lhe yellow plgmenLed urobllln apparenL ln urlne.
1he uroblllnogen ls reduced Lo sLercoblllnogen ln Lhe lnLesLlne and ls Lhen oxldlzed
Lo brown sLercobllln, whlch glves Lhe feces Lhelr characLerlsLlc color.

ln blllary obsLrucLlon, below-normal amounLs of con[ugaLed blllrubln reach Lhe
lnLesLlne for converslon Lo uroblllnogen. WlLh llmlLed uroblllnogen avallable for
reabsorpLlon and excreLlon, Lhe amounL of urobllln found ln Lhe urlne ls low. Plgh
amounLs of Lhe soluble con[ugaLed blllrubln enLer Lhe clrculaLlon where Lhey are
excreLed vla Lhe kldneys. 1hese mechanlsms are responslble for Lhe dark urlne and
pale sLools observed ln blllary obsLrucLlon.

Low urlne uroblllnogen may resulL from compleLe obsLrucLlve [aundlce or LreaLmenL
wlLh broad-specLrum anLlbloLlcs, whlch desLroy Lhe lnLesLlnal bacLerlal flora.
(CbsLrucLlon of blllrubln passage lnLo Lhe guL or fallure of uroblllnogen producLlon ln
Lhe guL.)


33) on LIVLk LN2MLS
My dear yln llng,

AL1, an enzyme ln llver cells, wlLh lesser amounLs ln Lhe kldneys, hearL, and skeleLal
muscles, and ls a relaLlvely speclflc lndlcaLor of acuLe llver cell damage. When such
damage occurs, AL1 ls released from Lhe llver cells lnLo Lhe bloodsLream, ofLen
before [aundlce appears, resulLlng ln abnormally hlgh serum levels LhaL may noL
reLurn Lo normal for days or weeks.

ln comblnaLlon, AL1 and AS1 are Lwo of Lhe mosL rellable markers of hepaLocellular
ln[ury or necrosls. Cf Lhe Lwo, AL1 |s more spec|f|c for hepat|c |n[ury because |t |s
present ma|n|y |n the cytoso| of the ||ver and |n |ow concentrat|ons e|sewhere. AS1
has cyLosollc and mlLochondrlal forms and ls presenL ln Llssues of Lhe llver, hearL,
skeleLal muscle, kldneys, braln, pancreas, and lungs, and ln whlLe and red blood
cells.

Markers for hlgh alcohol consumpLlon are carbohydraLe deflclenL Lransferrln (Cu1),
gamma gluLamyl Lransferase (CC1) and asparLaLe amlnoLransferase (AS1). 8u1 MosL
have falrly low senslLlvlLles and speclflclLles

An elevaLed serum AS1 ln relaLlon Lo serum AL1 (alanlne amlnoLransferase) ls llkely
an lndlcaLor LhaL alcohol has lnduced llver damage. 1hus, when AS1/AL1 raLlo ls
>1.3, Lhls ls consldered as hlghly suggesLlve LhaL alcohol ls Lhe cause of Lhe paLlenL's
llver paLhology.

Powever, many paLlenLs who doubLless consume hlgh amounLs of alcohol and
lndeed are alcohol-dependenL and dlsplay elevaLed serum amlnoLransferase levels
do noL show a hlgh AS1/AL1 raLlo. 1hls suggesLs LhaL addlLlonal facLors lead Lo Lhe
hlgh AS1/AL1 raLlo seen ln some paLlenLs. Cne such facLor may be the sever|ty of
the ||ver d|sease.

1he we||-recogn|sed h|gh AS1]AL1 rat|o |n a|coho||c ||ver d|sease |s, |n fact,
predom|nant|y found |n pat|ents whose d|sease |s advanced. ulfferenL, Lo some
exLenL posslbly lnLerrelaLed, reasons have been reporLed for Lhe hlgh AS1/AL1 raLlo
ln alcohollc llver dlsease:
l) a decreased hepaLlc AL1 acLlvlLy as healLhy hepaLocyLes decrease,
ll) pyrldoxal 3-phosphaLe depleLlon ln Lhe llvers of alcohollcs,
and
lll) mlLochondrlal damage leadlng Lo an lncrease ln serum acLlvlLy of mlLochondrlal
asparLaLe ln paLlenLs wlLh hlgh alcohol consumpLlon leadlng Lo hlgh AS1.

8u1 MosL paLlenLs wlLh hlgh alcohol consumpLlon do noL have an AS1/AL1 raLlo
above 1.

nence, remember that a h|gh AS1]AL1 rat|o |s suggest|ve of advanced a|coho||c
||ver d|sease, not [ust a|coho||sm.

Llver uAMACL ls seen wlLh lncreased AS1/AL1 raLlo ln paLlenLs. 1hls has also been
assoclaLed wlLh Lhe developmenL of clrrhosls ln nonalcohollc SLeaLohepaLlLls.
lurLhermore, a hlgh AS1/AL1 raLlo ln paLlenLs wlLh lncreased serum
amlnoLransferases has been reporLed ln chronlc vlral hepaLlLls, posslbly due Lo Lhe
same reasons.

AL1 ls presenL malnly ln Lhe cyLosol, whlle AS1 ln Lhe mlLochondrlas. Dur|ng events
of INILAMMA1ICN, as hepatocyte ce|| wa|| |ntegr|ty breaks down, AL1 w|||
|ncrease much much more than AS1, eg |n v|ra| hepat|t|s.

AL1 test|ng he|ps detect and eva|uate progress and treatment of acute hepat|c
d|sease, espec|a||y hepat|t|s, and c|rrhos|s.

Very h|gh AL1 |eve|s (up to S0 t|mes norma|) suggest v|ra| or severe drug-|nduced
hepat|t|s, or other hepat|c d|sease w|th extens|ve damage of ||ver ce||s. (AS1 |eve|s
are a|so e|evated but usua||y to a |esser degree.)

Moderate-to-h|gh |eve|s may |nd|cate |nfect|ous mononuc|eos|s, chron|c hepat|t|s,
|ntrahepat|c cho|estas|s or cho|ecyst|t|s, ear|y or |mprov|ng acute v|ra| hepat|t|s, or
severe hepat|c congest|on due to heart fa||ure.

S||ght-to-moderate e|evat|ons of AL1 (usua||y w|th h|gher |ncreases |n AS1 |eve|s)
may appear |n any cond|t|on that produces acute hepatoce||u|ar (||ver ce||) |n[ury,
such as act|ve c|rrhos|s, and drug-|nduced or a|coho||c hepat|t|s.

Marglnal elevaLlons occaslonally occur ln acuLe myocardlal lnfarcLlon (hearL aLLack),
reflecLlng secondary hepaLlc congesLlon or Lhe release of small amounLs of AL1 from
hearL Llssue.

nowever |n the events of CLLL DLA1n, AS1 w||| predom|nant|y |ncrease as ce||
death re|ease the AS1 enzymes from the m|tochondr|a eg |n ||ver c|rrhos|s, and
myocard|a| |nfarct.

AS1 levels flucLuaLe ln response Lo Lhe exLenL of cellular necrosls and Lherefore may
be Lemporarlly and mlnlmally elevaLed early ln Lhe dlsease process, and exLremely
elevaLed durlng Lhe mosL acuLe phase. Depend|ng on when the |n|t|a| samp|e was
drawn, AS1 |eve|s can r|se- |nd|cat|ng |ncreas|ng d|sease sever|ty and t|ssue
damage- or fa||- |nd|cat|ng d|sease reso|ut|on and t|ssue repa|r. 1hus, the re|at|ve
change |n AS1 va|ues serves as a re||ab|e mon|tor|ng mechan|sm.

May Lhls llLLle yeL lmporLanL concepL helps ln your fuLure Ll1 lnLerpreLaLlon.


34) CN kLILLkLS
uear ?ln Llng,

1he nC8MAL Superflclal reflexes

Superflclal reflexes are moLor responses Lo scraplng Lhe skln.
1hey are graded slmply as presenL or absenL and markedly asymmeLrlcal responses
would be consldered abnormal.

1hese reflexes are VLk d|fferent from the musc|e stretch ref|exes |n that the
sensory s|gna| has to not on|y reach the sp|na| cord, but a|so must ascend the cord
to reach the bra|n. 1he motor ||mb then has to descend the sp|na| cord to reach
the motor neurons . As can be seen from Lhe descrlpLlon, Lhls ls a polysynapLlc
reflex.

1hls can be abollshed by lower moLor neuron damage or desLrucLlon of Lhe sensory
paLhways from Lhe skln LhaL ls sLlmulaLed. Powever, Lhe uLlllLy of superflclal reflexes
ls LhaL Lhey are decreased or abollshed by condlLlons LhaL lnLerrupL Lhe paLhways
beLween Lhe braln and splnal cord (such as wlLh splnal cord damage).

Classlc examples of superflclal reflexes lnclude the abdom|na| ref|ex, the cremaster
ref|ex and the norma| p|antar response.

1he abdomlnal reflex lncludes conLracLlon of abdomlnal muscles LhaL ls sLlmulaLed
by scraplng Lhe skln superflclally and rapldly along a dermaLome Lowards Lhe
umblllcus . 1hls conLracLlon can be seen as a brlsk conLracLlon of Lhe abdomlnal
muscles wlLh Lhe umblllcus movlng Lowards Lhe sLlmull.

1he cremasLer reflex ls produced by scraLchlng Lhe skln of Lhe medlal Lhlgh, whlch
should produce a brlsk and brlef elevaLlon of Lhe LesLls on LhaL slde.


1he normal planLar response occurs when scraLchlng Lhe sole of Lhe fooL from Lhe
heel along Lhe laLeral aspecL of Lhe sole and Lhen across Lhe ball of Lhe fooL Lo Lhe
base of Lhe greaL Loe. 1hls normally resulLs ln flexlon of Lhe greaL Loe (a "down-golng
Loe") and, lndeed, all of Lhe Loes.

1he "anal wlnk" ls a conLracLlon of exLernal anal sphlncLer when Lhe skln near Lhe
anal openlng ls scraLched. 1hls ls ofLen abollshed ln splnal cord damage (along wlLh
oLher superflclal reflexes ).

And now Lhe "aLhologlcal reflexes"

1he besL known (and mosL lmporLanL) of Lhe so-called "paLhologlcal reflexes" ls Lhe
8ablnskl response (upgolng Loe, exLensor response). 1he full expresslon of Lhls reflex
lncluded exLenslon of Lhe greaL Loe and fannlng of Lhe oLher Loes . lL ls acLually a
superflclal reflex LhaL ls ellclLed ln Lhe same manner as Lhe planLar response (l.e.,
scraLchlng along Lhe laLeral aspecL of Lhe sole of Lhe fooL and Lhen across Lhe ball of
Lhe fooL Loward Lhe greaL Loe). 1hls ls a prlmlLlve wlLhdrawal Lype response LhaL ls
normal for Lhe flrsL few monLhs of llfe and ls suppressed by suprasplnal acLlvlLy
someLlme before 6 monLhs of age.

uamage Lo Lhe descendlng LracLs from Lhe braln (elLher above Lhe foramen magnum
or ln Lhe splnal cord) promoLes a reLurn of Lhls prlmlLlve proLecLlve reflex, whlle aL
Lhe same Llme abollshlng Lhe normal planLar response. 1he appearance of Lhls reflex
suggesLs Lhe presence of an upper moLor neuron leslon.


3S) CN SLL
uear yln llng,

1hls l hope wlll help you remember

C- Cral ulcer
8- malar 8ash
u- ulscold rash
L- LxaggeraLed phoLosenslLlvlLy
8- 8enal dlsorders (proLelnurla, cellular casLs)

P- PaemaLology dlsorders (haemolyLlc anemla, leukopenla, lymphopenla,
LhrombocyLopenla)
l- lmmunologlcal dlsorders (anLl-unA anLlbody, anLl-Sm, anLlphosphollpld anLlbody)
S- SeroslLls

A- AnA
n- neurologlcal problems
A- ArLhrlLls

1. 9S of SLL are ANA +ve.
2. S0 dsDNA +ve, but |s spec|f|c for SLL.
3. 2S kI +ve.
rof Lsha : Lven lf you forgeL Lhe pnemonlc, remember Lhere are 4 mucocutaneous
features,(ma|ar rash,photosens|t|ve rash,d|sco|d rash and ora| u|cer),4 system|c
|nvo|vement( CNS,seros|t|s,k|dney and arthr|t|s) and 3 |ab f|nd|ng(
neamato|ogy,Immuno|ogy and ANA stands on |ts own) 8ecenL addlLlon ln lab
feaLures are poslLlve anLl Sm anLlbody,anLlphosphollpls anLlbody,and low
complemenLs,along wlLh dlrecL poslLlve coomb's LesL.


36) CN MCNCIILAMLN1 test|ng
uear ?ln Llng,

Are you famlllar wlLh MonofllamenL sensory LesLlng devlces whlch conslsL of a slngle
sLrand of nylon (Lyplcally aLLached Lo a plasLlc or paper handle) LhaL can produce a
characLerlsLlc downward force when buckled onLo a surface?
Are you aware LhaL Lhey come ln dlfferenL slzes?

1he monofllamenLs commonly used Lo screen for sensory neuropaLhy are 4.17, 3.07,
and 6.10. 1he use of a slngle 3.07 monofllamenL ls Lhe accepLed sLandard ln medlcal
pracLlce Lo screen for Lhe mlnlmum level of proLecLlve sensaLlon ln Lhe fooL. 1en
grams of reproduclble buckllng sLress force are requlred Lo bend Lhe 3.07
monofllamenL.

Why do we use monofllamenL LesLlng? Why do we noL [usL use our usual pln, coLLon
and Lunlng fork??

When Lhe monofllamenL bends, lLs Llp ls exerLlng a pressure of 10 grams (Lherefore
Lhls monofllamenL ls ofLen referred Lo as Lhe 10gram monofllamenL). lf Lhe paLlenL
cannoL feel Lhe monofllamenL aL cerLaln speclfled slLes on Lhe fooL, he/she has losL
enough sensaLlon Lo be aL rlsk of developlng a neuropaLhlc ulcer.
1esLlng of dlabeLlc paLlenLs for proLecLlve sensaLlon may be slmpllfled Lo LesLlng
under boLh flrsL meLaLarsal heads. lf a paLlenL cannoL sense Lhe appllcaLlon under
elLher flrsL meLaLarsal head, he or she probably has losL proLecLlve sensaLlon and
should be consldered Lo be aL rlsk for undeLecLed ln[ury.

Cenerally, no person wlLh a fooL ulceraLlon could feel Lhe 3.07 (10g) fllamenL,
concludlng LhaL monofllamenLs are an effecLlve, lnexpenslve and slmple screenlng
devlce ln ldenLlfylng Lhe 'aL rlsk' fooL.

ln conLrasL, a person who can feel Lhe 10-gram fllamenL ln Lhe selecLed slLes ls aL
reduced rlsk for developlng ulcers.
1he paLlenL musL noL waLch whlle Lhe examlner applles Lhe fllamenL.
re-1esL Lhe monofllamenL on Lhe paLlenL's hand or sLernum so he/she knows whaL
Lo anLlclpaLe.

1yplcally we LesL flve slLes and documenL Lhe flndlngs. 1he number of slLes may vary
from cenLre Lo cenLre.
Apply Lhe monofllamenL perpendlcular Lo Lhe skln's surface
Apply sufflclenL force Lo cause Lhe fllamenL Lo bend or buckle

ls Apply Lhe fllamenL along Lhe perlmeLer and nC1 Cn an ulcer, callus, scar or
necroLlc Llssue. uo noL allow Lhe fllamenL Lo sllde across Lhe skln or make repeLlLlve
conLacL aL Lhe LesL slLe.
Pave paLlenLs ldenLlfy aL whlch Llme Lhey were Louched. 1o avold guesslng,
randomlze Lhe sequence of applylng Lhe fllamenL LhroughouL Lhe examlnaLlon.
aLlenLs should have Lhelr feeL examlned aL leasL annually for lmpalred sense of
pressure, vlbraLlon, paln, or LemperaLure, whlch ls characLerlsLlc of perlpheral
neuropaLhy.

ressure sense ls besL LesLed wlLh a monofllamenL esLheslomeLer as Lhls plcks up
paLlenLs wlLh hlgh rlsk of dlabeLlc ulcers


?ln Llng,
1he overall rlsk of developlng a dlabeLlc fooL ulcer ls deLermlned by a comblnaLlon of
facLors.

ln general, Lhe rlsk ls hlgher lf:

neuropaLhy ls more severe (because more sensaLlon ls losL and mulLlple small
Lrauma breaks Lhe skln)

erlpheral vascular dlsease ls more severe (because Lhere ls less clrculaLlon Lo brlng
enough oxygen Lo repalr Llssue damage. !usL look aL Lhe dry black feeL wlLh curled
up nalls and you see feeL whlch are deserLs)

1here are coexlsLlng abnormallLles of Lhe shape of Lhe fooL whlch make Lhe local
effecLs of neuropaLhy or vascular dlsease more severe (because lL lncreases local
pressure and callus, heavens leL us ban all Lhose fashlonable buL cruel fooLwear LhaL
ladles wear as lL deforms Lhe feeL lnLo an abnormal shape)

1he paLlenL who ls unable Lo pracLlse reasonable self care of Lhe feeL and Lo prevenL
Lrauma (because Lhere are more chances of damaglng Lhe feeL wlLh fungal lnfecLlons
ln Lhe webs, poor nall hyglene and cuLLlng)

1he dlabeLlc conLrol ls very poor (because of suscepLlblllLy Lo lnfecLlon and poor
wound heallng)

1here ls a pasL hlsLory of fooL ulceraLlon due Lo dlabeLes (because all Lhe above
facLors perslsL)
uear ?ln Llng,

eople ofLen ask whlch ls Lhe earllesL abnormallLy and expecL a slngle answer LhaL ls
dogmaLlc. 1he LruLh ls however much more complex and Lhe answer ls "lL varles!"

Sensory or sensorlmoLor dlsLal polyneuropaLhy ls Lhe mosL common of Lhe dlabeLlc
neuropaLhles. WlLh Lhls, numbness and paresLheslas begln ln Lhe Loes, and gradually
and lnsldlously ascend Lo lnvolve Lhe feeL and lower legs. very common, we see lL all
Lhe Llme.

WlLh a sensory or sensorlmoLor dlsLal polyneuropaLhy, boLh llghLly myellnaLed and
unmyellnaLed small nerve flbers and Lhe myellnaLed large nerve flbers are affecLed.
Small and large flber dysfuncLlon occurs ln varylng comblnaLlons,
however, ln mosL cases, Lhe earllesL deflclLs lnvolve Lhe small nerve flbers.

Ieatures character|st|c of a sma|| f|ber per|phera| neuropathy |nc|ude burn|ng or
|anc|nat|ng pa|n, hypera|ges|a, paresthes|as and dysesthes|as, **def|c|ts |n pa|n
and temperature percept|on** |ead|ng to foot u|cerat|on.

Ieatures character|st|c of |arge f|ber per|phera| neuropathy |nc|ude the |oss of
pos|t|on and v|brat|on percept|on sense and |oss of deep tendon ref|exes, tested
w|th tun|ng fork and Ank|e [erks.

So based on Lhls whaL wlll you, yln llng, selecL as a mode for screenlng whlch musL of
course plck up Lhe paLhology early!?




37) CN ISCLA1LD kAISLD GAMMA G1
uear ?L,

8alsed Camma C1 ln lsolaLlon ls a very common flndlng
lL ls lrom hepaLocyLes and blllary eplLhellal cells, pancreas, renal Lubules and
lnLesLlne. very senslLlve buL non-speclflc
lL ls 8alsed ln An? llver dlsease hepaLocellular or cholesLaLlc 8uL usefulness ls llmlLed
lL helps Conflrm hepaLlc source for a ralsed AL
Alcohol lnduces lL
As lL ls an Laslly lnduced enzyme- many urugs elevaLes lL
*ls noLe LhaL an lsolaLed lncrease does noL requlre any furLher evaluaLlon, suggesL
waLch and rpL 3/12 and only lf oLher Ll1's become abnormal Lhen lnvesLlgaLe

38) CN CM 1CkICI1
uear ?L,
Are you aware LhaL araceLamol LoxlclLy can occur ln much lower doses ln cerLaln
clrcumsLances eg

Alcohol use
lasLlng sLaLe- uepleLlon of gluLaLhlone
8eware of overdoslng ln Lhe fasLlng paLlenL wlLh paln eg. posL surgery!!!
So lf you [og, geL dehydraLed, low gluLaLhlone now and have muscle aches for whlch
you Lake CM, you may have llver damage!!

39) CN ALCCnCL
uear ?ln Llng,
our Musllm frlends are absoluLely rlghL wlLh alcohol prohlblLlon. And Lhe 8uddhlsL
recepLs also do noL allow Alcohol consumpLlon.

Alcohol, a very slmple molecule ls probably Lhe mosL wldely used drug ln Lhe world.
lL ls dlsLrlbuLed Lo all Lhe organs and flulds of Lhe body, buL lL ls ln Lhe braln LhaL
alcohol exerLs mosL of lLs effecLs. Llke oLher general anesLheLlcs, alcohol ls a cenLral
nervous sysLem depressanL. ln general, lLs effecLs are proporLlonal Lo lLs
concenLraLlon ln Lhe blood.

?ln Llng, Pow does Lhe body handle alcohol?

Alcohol ls rapldly absorbed from Lhe gasLrolnLesLlnal LracL lnLo Lhe bloodsLream and
from Lhere lL ls dlsLrlbuLed LhroughouL Lhe oLher bodlly flulds and Llssues. Alcohol ls
prlnclpally meLabollzed by Lhe llver lnLo aceLaldehyde, wlLh Lhe remalnder belng
excreLed ln Lhe urlne.
Cn average, |t takes the ||ver about an hour to break down one un|t of a|coho| --
Lhe amounL Lyplcally found ln 12 ounces of beer, 4 ounces of wlne or one ounce of
30 proof hard llquor.

8lood alcohol levels decllne aL a flxed raLe lrrespecLlve of Lhe amounL consumed.
1he more consumed, Lhe longer lL Lakes Lo be meLabollzed. AddlLlonally, blood
levels are greaLly, and lnversely, lnfluenced by body welghL. 1he th|nner you are,
the greater the a|coho| b|ood |eve| for any g|ven amount of a|coho| consumed.
8ecause of Lhese facLors, blood levels may remaln elevaLed for many hours afLer Lhe
lasL drlnk.

Alcohol may lmpalr LemperaLure regulaLlon boLh ln Lhe cold, and ln Lhe heaL, ln
counLrles wlLh exLreme cllmaLes, Lhls can klll. lL ls also a poLenL dlureLlc and Lhls may
lead Lo dehydraLlon.

?ln Llng, WhaL are Lhe long Lerm adverse effecLs of alcohol?

1he chronlc abuse of alcohol may cause numerous adverse healLh effecLs whlch
lnclude:

Chronlc alLeraLlon of braln and nerve funcLlon
Weakenlng of hearL muscle
1esLlcular shrlnkage and male breasL enlargemenL
lmpoLency
LlevaLed Lrlglycerldes
laL deposlLs ln Lhe llver
Clrrhosls and llver fallure
8lood-cloLLlng abnormallLles
ancreaLlLls
vlLamln deflclencles
Chronlc skln alLeraLlons
ueaLh

Chronlc moderaLe eLhanol lngesLlon by young female mlce resulLs ln decreased
ferLlllzaLlon, embryo growLh reLardaLlon, and abnormal embryo developmenL ln
vlLro. 1he cardlovascular consequences of heavy eLhanol consumpLlon are several. lf
eLhanol exposure occurs prenaLally aL a perlod when Lhe hearL of Lhe lnfanL ls
developlng, Lhen sLrucLural damage ls observed and manlfesLs as dlmlnlshed
capaclLy of Lhe hearL Lo funcLlon properly. lf Lhe cardlovascular sysLem ls exposed Lo
excesslve eLhanol laLer ln llfe, Lhen a varleLy of problems can manlfesL, mosL
promlnenLly are cardlomyopaLhy, hyperLenslon, sLroke and cardlac arrhyLhmlas.

Cardlac arrhyLhmlas have been observed afLer boLh acuLe lnLake of large amounLs of
eLhanol and afLer chronlc alcohol consumpLlon. lor example, eLhanol lnLake over a
long weekend may resulL ln elecLrophyslologlcal anomalles referred Lo as "hollday
hearL syndrome", whereas sudden cardlac deaLh has been assoclaLed wlLh
alcohollsm. A number of hypoLheses have been advanced Lo explaln Lhe
dlsLurbances ln cardlac rhyLhms. 1hese lnclude scarrlng of Lhe hearL muscle,
alLeraLlons ln Lhe chemlcals, whlch lnfluence hearL funcLlon such as elecLrolyLes and
caLecholamlnes, and alLeraLlons ln Lhe amounL of oxygen comlng Lo Lhe hearL.

1here appear Lo be several mechanlsms by whlch eLhanol can lead Lo
cardlomyopaLhy. 1hese lnclude Lhe followlng:

1. an alLeraLlon ln Lhe flow of calclum lons ln Lhe cardlac muscle, whlch ln Lurn
reduces Lhe efflclency by whlch calclum acLlvaLes muscle conLracLlon,
2. modlflcaLlon of Lhe acLlon of conLracLlle proLelns, acLln and myosln,
3. reducLlon ln Lhe synLhesls of proLelns needed for conLracLlon and energy,
4. an lnfluence of deleLerlous eLhanol meLabollLes (aceLaldehyde) and free radlcals,
and
3. acLlvaLlon of genes whlch may promoLe cell deaLh.

?ln Llng, does alcohollsm cause Cancer?

ConsumpLlon of alcohollc beverages ls causally relaLed Lo cancers of Lhe mouLh,
pharynx, larynx and esophagus and LhaL sLudles lndlcaLe LhaL Lhe rlsk ls mosL
pronounced among smokers and aL Lhe hlghesL levels of consumpLlon.

1here ls evldence LhaL suggesLs a llnk beLween alcohollc beverage consumpLlon and
cancer of Lhe llver and breasL.

1here are some clrcumsLances under whlch dlabeLlcs should noL drlnk alcohol ln any
amounL. 1he key for Lhose wlLh dlabeLes ls Lo undersLand whaL condlLlons can be
worsen lf Lhey consume alcohol.

Accordlng Lo Lhe Amerlcan ulabeLes AssoclaLlon, drlnklng alcohol ls a poor cholce lf
dlabeLlcs have Lhe followlng condlLlons:

nerve damage ln Lhe arms or legs.
ulabeLlc eye dlsease.
Plgh blood pressure.
Plgh levels of Lrlglycerldes.
Alcohol can damage nerve cells, even llghL drlnklng can cause nerve damage. lor
dlabeLlcs wlLh nerve damage drlnklng can lncrease Lhe paln, numbness, Llngllng or
burnlng sensaLlon assoclaLed wlLh dlabeLlc nerve damage.
lor dlabeLlcs wlLh eye dlsease sympLoms, heavy drlnklng can make Lhe condlLlon
worse and heavy drlnklng ls deflned as Lhree or more drlnks durlng one day.
ulabeLlcs who also have hlgh blood pressure should also noL drlnk alcohol.

ls remember LhaL Alcohol lncreases Lhe amounL of Lrlglycerldes ln Lhe blood. Lven
very llghL drlnklng, deflned as Lwo drlnks a week, can lncrease Lrlglycerlde levels.
ulabeLlcs who have hlgh Lrlglycerldes should noL drlnk alcohol aL all.

?ln Llng, whaL are Lhe Sexual effecLs of alcohol?

Soon afLer consumlng alcohol, ls found Lhe followlng common effecLs:
Alcohol has a dlslnhlblLlng" effecL, whlch can make people loosen up" and feel
more comforLable lnlLlaLlng or engaglng ln sex.
Alcohol may make you feel more soclally confldenL and ln small quanLlLles may
faclllLaLe more soclallzlng and sexual communlcaLlon.
ln small amounLs alcohol has been reporLed Lo have a poslLlve lmpacL on sexual
deslre and arousal.
AL Lhe same Llme, research shows LhaL even afLer a few drlnks sexual response ls
reduced.
ln large amounLs alcohol makes sex dlfflculL Lo lmposslble. Whlle ln moderaLe
amounLs alcohol can have an lmpacL on engaglng ln rlsky sexual behavlor, alLhough
Lhls lmpacL ls noL fully undersLood.
As drlnklng lncreases boLh men and women wlll experlence a reducLlon ln sexual
arousal, men may have dlfflculLy geLLlng erecLlons, and boLh men and women may
have dlfflculLy experlenclng orgasm.

yln llng, whaL are Lhe Long Lerm sexual effecLs of alcohol?

Chronlc alcohol abuse, or alcohollsm, lnevlLably has a devasLaLlng effecL on
sexuallLy, lncludlng:
LrecLlle dlsorders and dysfuncLlon ln men
Loss of sexual deslre, slgnlflcanL decrease ln sexual arousal for men and women
ulfflculLy experlenclng orgasm for men and women

?ln Llng, whaL causes llushlng ln some people afLer drlnklng alcohol?

SLudles of auLopsy llver speclmens from lndlvlduals of dlfferenL raclal groups
revealed a polymorphlsm ln a|coho| dehydrogenase (ADn) and a|dehyde
dehydrogenase (ALDn). AbouL 83 of Lhe !apanese llvers had an aLyplcal AuP and
32 of Lhe llvers an unusual ALuP.

uaLa on Lhe dlsLrlbuLlon of phenoLypes ln random Luropean and !apanese
populaLlon as well as famlly sLudles suggesL a dlrecL relaLlonshlp beLween Lhe lack of
low km lsozyme of ALuP and alcohol-lnduced blologlcal senslLlvlLy. Alcohol
senslLlvlLy ls qulLe common ln lndlvlduals of Mongolold orlgln and mlghL be due Lo
delayed oxldaLlon of aceLaldehyde by an unusual Lype of ALuP.

Many people of LasL Aslan descenL have a mutat|on |n the|r a|coho| dehydrogenase
gene that makes th|s enzyme unusua||y effect|ve at convert|ng ethano| to
aceta|dehyde, and abouL half of such people also have a form of aceta|dehyde
dehydrogenase wh|ch |s |ess effect|ve at convert|ng aceta|dehyde to acet|c ac|d.
1hls comblnaLlon causes Lhem Lo suffer from Lhe alcohol flush reacLlon, ln whlch
aceLaldehyde accumulaLes afLer drlnklng, leadlng Lo severe and lmmedlaLe hangover
sympLoms.


8uL lL ls noL [usL alcohol whlch causes flushlng! ls Lhlnk of oLher causes as well!


40) CN 8LNCL ICNLS kC1LIN
uear ?L,


noL many medlcal sLudenLs know abouL Lhls LesL now. When l was a sLudenL, rof
llorence Wang would make us Lake urlne and LesL lL aL Lhe lab ourselves. Pence
Lhese are sheared lnLo my memory.

urlne ls Lhe besL speclmen ln whlch Lo look for 8ence !ones proLelns whlch lf presenL
suggesLs MulLlple Myeloma. roLelns are usually Loo large Lo move Lhrough a
healLhy kldney, from Lhe blood lnLo Lhe urlne. 8ence Iones prote|ns are an
except|on. 1hey are sma|| enough to move qu|ck|y and eas||y through the k|dney
|nto the ur|ne.

A rout|ne d|pst|ck ur|na|ys|s w||| not detect 8ence Iones prote|ns. 1here are several
meLhods used by laboraLorles Lo deLecL and measure Lhese proLelns.

1he classlc 8ence !ones reacLlon lnvolves heat|ng ur|ne to 60C |n a test tube p|aced
|n a waterbath. At th|s temperature, the 8ence Iones prote|ns w||| c|ump. 1he
c|ump|ng d|sappears when the ur|ne |s further heated to bo|||ng and reappears
when the ur|ne |s coo|ed.

1hls slmple LesL wlll reveal wheLher or noL 8ence !ones proLelns are presenL, buL noL
how much ls presenL.



41) CN MCCAkDIAL C2 DLMAND
uear ?L,

WhaL ls Myocardlal C2 demand?

Myocardlal C2 demand ls deLermlned malnly by hearL raLe, sysLollc wall Lenslon, and
conLracLlllLy, hence narrowlng of a coronary arLery Lyplcally resulLs ln anglna LhaL
occurs durlng exerLlon and ls relleved by resL. Slmple buL 1haL's for Lhe sLable
plaques of course.

C: Pow dld Wllllam Peberden descrlbe Classlc anglna?

|s note a c|ass|c- Ang|na |mmob|||ses the pat|ent from whatever he |s do|ng -
he]she S1CS!

ln addlLlon Lo exerLlon, cardlac workload can be lncreased by dlsorders such as
lnLercurrenL lllnesses, fever, hyperLenslon, aorLlc sLenosls, aorLlc regurglLaLlon, or
hyperLrophlc cardlomyopaLhy.

C: WhaL are Lhe Classlcal resenLaLlon sympLoms of AorLlc sLenosls?

LvP from whaLever cause can also decrease relaLlve myocardlal perfuslon because
myocardlal mass ls lncreased (causlng decreased dlasLollc flow).

A decreased C2 supply, as ln severe anemla or hypoxla, can preclplLaLe or aggravaLe
anglna.

ln sLable anglna, Lhe relaLlonshlp beLween workload or demand and lschemla ls
usually relaLlvely predlcLable. 1he greaL !ohn PunLer predlcLed LhaL hls llfe ls ln Lhe
hands of any rascals LhaL lnfurlaLed hlm, l assumed he was referlng Lo hls med
sLudenLs buL nope he dled afLer a hosplLal board meeLlng from a masslve AMl. 1old
you faculLy meeLlngs are dangerous affalrs!

As Lhe myocardlum becomes lschemlc, venLrlcular funcLlon deLerloraLes. LefL
venLrlcular (Lv) dlasLollc pressure usually lncreases durlng anglna, someLlmes
lnduclng pulmonary congesLlon and dyspnea. 8emember 'anglna equlvalenLs' !
1he exacL mechanlsm by whlch lschemla produces dlscomforL ls unclear buL may
lnvolve nerve sLlmulaLlon by hypoxlc meLabollLes.

C: WhaL are Lhe llmlLaLlons of Lhe LCC?

1he LCC reveals Lhe hearL raLe and rhyLhm only durlng Lhe Llme LhaL Lhe LCC ls
Laken. A spoL plcLure only

1he LCC can ofLen be normal or nearly normal ln paLlenLs wlLh undlagnosed
coronary arLery dlsease (false negaLlve resulLs.)
Cn Lhe oLher hand, many "abnormallLles" LhaL appear on Lhe LCC may Lurn ouL Lo
have no medlcal slgnlflcance (false poslLlve resulLs).

Many people wlLh lschaemlc hearL dlsease have a normal LCC aL resL. uurlng
exerclse Lhe hearL beaLs fasLer and needs more oxygen. lf one or more of Lhe
coronary arLerles are narrowed, parL or parLs of Lhe hearL muscle do noL geL enough
oxygen. 1hls can cause Lhe LCC Lraclng Lo become abnormal.

1he degree of abnormallLy on Lhe exerclse LCC Lraclng can glve a good ldea of Lhe
severlLy of Lhe dlsease. 1herefore, an exerclse LCC LesL ls ofLen done Lo help Lo
declde lf furLher lnvesLlgaLlons ls needed. 8uL l have colleagues who go sLralghL Lo a
C1 anglo buL LhaL's anoLher sLory.

8ecause anglna resolves qulckly wlLh resL, LCC rarely can be done durlng an aLLack
excepL durlng sLress LesLlng. lf done durlng anglna, LCC ls llkely Lo show reverslble
lschemlc changes: 1 wave lnverslon, S1-segmenL depresslon (Lyplcally), S1-segmenL
elevaLlon (S1-segmenL elevaLlon raLher Lhan depresslon occurs durlng aLLack ln
varlanL anglna), decreased 8-wave helghL, lnLravenLrlcular or bundle branch
conducLlon dlsLurbances, and arrhyLhmla (usually venLrlcular exLrasysLoles).

lf Lhe LCC ls nC8MAL desplLe paln, we can only be confldenL LhaL Lhe dlsease ls
llghLly nC1 severe and ouLlook good, buL we cannoL exclude lL lf Lhe hlsLory ls
1?lCAL.
1he resLlng LCC ls ofLen normal ln sLable anglna pecLorls ln Lhe absence of a
prevlous Ml or a cause for LvP. Abnormal LCC changes are more common wlLh
unsLable anglna pecLorls.

1he resLlng LCC (and usually Lv funcLlon) aL resL ls normal ln abouL 30 of paLlenLs
wlLh a Lyplcal hlsLory of anglna pecLorls, even Lhose wlLh exLenslve 3-vessel dlsease.
ln Lhe remalnlng 70, Lhe LCC shows evldence of prevlous lnfarcLlon, hyperLrophy,
or nonspeclflc S1-segmenL and 1-wave abnormallLles.
ln men wlLh chesL dlscomforL suggesLlng anglna, sLress LCC LesLlng has a speclflclLy
of 70, senslLlvlLy ls 90. SenslLlvlLy ls slmllar ln women, buL speclflclLy ls lower,
parLlcularly ln women < 33 (< 70). Powever, women are more llkely Lhan men Lo
have an abnormal resLlng LCC when CAu ls presenL (32 vs 23). AlLhough
senslLlvlLy ls reasonably hlgh, exerclse LCC can mlss severe CAu (even lefL maln or 3-
vessel dlsease). l had an emlnenL professor who had a 'normal' sLress LesL a week
before hls faLal lnfarcL.

ln paLlenLs wlLh aLyplcal sympLoms, a negaLlve sLress LCC usually rules ouL anglna
pecLorls and CAu, buL a poslLlve resulL may or may noL represenL coronary lschemla
and lndlcaLes need for furLher LesLlng.

1he PlS1C8? ls Lhe MCS1 lmporLanL dlagnosLlc feaLure, Lhe speclflclLy of S1-1 and 1
wave abnormallLles ls provlded more by Lhe cllnlcal clrcumsLances ln whlch Lhe LCC
changes are found Lhan by Lhe parLlcular changes Lhemselves.

ln paLlenLs who presenLs wlLh a hlsLory suggesLlve of AMl wlLhln Lhe lasL 2 - 3 hours,
a normal/nondlagnosLlc lnlLlal LCC predlcLs low rlsk. 1hls ls Lhe reassurance of Lhe
"normal flndlng" buL lL cannoL LxCLuuL Lhe dlagnosls, hence we need follow-up
LCCs, and blood LesLs.

lease reallse LhaL 3-10 of Ml paLlenLs have lnlLlal normal LCC!
Cf course, 23 of paLlenLs wlLh mlssed Ml had mlsread LCCs!!

lL ls lmporLanL Lo compare wlLh prlor LCCs lf avallable for Lhls lncreases SpeclflclLy!
Pave a hlgh level of susplclon when faclng a Lyplcal hlsLory and seelng LCC Markers
of underlylng CAu llke
Lg
LefL venLrlcular PyperLrophy wlLh or wlLhouL 'SLraln aLLern',
S1 segmenL changes, how deep ls Lhe S1 depresslon or elevaLlon,
1 Wave changes,
C Waves ln 2 conLlguous leads Lo suggesL prevlous evenLs,
Loss of rogresslon of 8 waves Lo suggesL prevlous evenLs,
LefL 8undle 8ranch 8lock or oLher conducLlon changes

Cn Lhe oLher hand, some people have "abnormal" LCCs aL basellne buL Lhls may be
normal for Lhem. lL ls lmporLanL LhaL an elecLrocardlogram be compared Lo prevlous
Lraclngs. 1he PlsLory cannoL be over-emphaslzed for lLs lmporLance ln dlagnosls
desplLe all our modern Lechnologles.
l hope you learn Lhls well.
42) CN kLILLkLS!
uear ?ln Llng,

1oday l demonsLraLed Poffman's and Chaddock's slgn ln a paLlenL Lo my sLudenLs aL
my cllnlc. 1he paLlenL's planLar response was equlvocal buL Chaddock's slgn was
crysLal clear. 1o my horror Lhe 2 klddles dld nC1 know anyLhlng abouL Lhe 2 slgns.

WhaL are Lhey??

Poffmann's slgn, named afLer Lhe Cerman neurologlsL, !ohann Poffmann (born
1837, 8helnhesse, dled 1919, Peldelberg), ls a flndlng ellclLed by a reflex LesL whlch
verlfles Lhe presence or absence of problems ln Lhe corLlcosplnal LracL. lL ls also
known as Lhe flnger flexor reflex.
1he LesL lnvolves Lapplng Lhe nall or fllcklng Lhe Lermlnal phalanx of Lhe Lhlrd or
fourLh flnger. A poslLlve response ls seen wlLh flexlon of Lhe Lermlnal phalanx of Lhe
Lhumb and lndex flnger.


8elaLlon Lo 8ablnskl slgn

Poffmann's slgn ls ofLen consldered Lhe upper llmb equlvalenL of Lhe 8ablnskl's slgn
because lL, llke Lhe 8ablnskl slgn, lndlcaLes upper moLor neuron dysfuncLlon. 8u1 lLs
mechanlsm dlffers conslderably from Lhe 8ablnskl whlch ls also known as Lhe planLar
reflex, Poffmann's slgn lnvolves a monosynapLlc reflex paLhway ln 8exed lamlna lx
of Lhe splnal cord, normally fully lnhlblLed by descendlng lnpuL. 1he paLhways
lnvolved ln Lhe planLar reflex are more compllcaLed, and dlfferenL sorLs of leslons
may lnLerrupL Lhem. 1hls facL has led some Lo re[ecL any analogles beLween Lhe
flnger flexor reflex and Lhe planLar response.

Superflclal reflexes are moLor responses Lo scraplng Lhe skln.
1hey are graded slmply as presenL or absenL and markedly asymmeLrlcal responses
would be consldered abnormal.
1hese reflexes are vL8? dlfferenL from Lhe muscle sLreLch reflexes ln LhaL Lhe
sensory slgnal has Lo noL only reach Lhe splnal cord, buL also musL ascend Lhe cord
Lo reach Lhe braln. 1he moLor llmb Lhan has Lo descend Lhe splnal cord Lo reach Lhe
moLor neurons. 1hls ls a polysynapLlc reflex.

1hls can be abollshed by lower moLor neuron damage or desLrucLlon of Lhe sensory
paLhways from Lhe skln LhaL ls sLlmulaLed. Powever, Lhe uLlllLy of superflclal reflexes
ls LhaL Lhey are decreased or abollshed by condlLlons LhaL lnLerrupL Lhe paLhways
beLween Lhe braln and splnal cord (such as wlLh splnal cord damage).

Classlc examples of superflclal reflexes lnclude Lhe abdomlnal reflex, Lhe cremasLer
reflex and Lhe normal planLar response.

1he abdomlnal reflex lncludes conLracLlon of abdomlnal muscles LhaL ls sLlmulaLed
by scraplng Lhe skln superflclally and rapldly along a dermaLome Lowards Lhe
umblllcus. 1hls conLracLlon can be seen as a brlsk conLracLlon of Lhe abdomlnal
muscles wlLh Lhe umblllcus movlng Lowards Lhe sLlmull.

1he cremasLer reflex ls produced by scraLchlng Lhe skln of Lhe medlal Lhlgh, whlch
should produce a brlsk and brlef elevaLlon of Lhe LesLls on LhaL slde.

1he normal planLar response occurs when scraLchlng Lhe sole of Lhe fooL from Lhe
heel along Lhe laLeral aspecL of Lhe sole and Lhen across Lhe ball of Lhe fooL Lo Lhe
base of Lhe greaL Loe. 1hls normally resulLs ln flexlon of Lhe greaL Loe (a "down-golng
Loe") and, lndeed, all of Lhe Loes.

1he "anal wlnk" ls a conLracLlon of exLernal anal sphlncLer when Lhe skln near Lhe
anal openlng ls scraLched. 1hls ls ofLen abollshed ln splnal cord damage (along wlLh
oLher superflclal reflexes ).

"aLhologlcal reflexes"

1he besL known (and mosL lmporLanL) of Lhe so-called "paLhologlcal reflexes" ls Lhe
8ablnskl response (upgolng Loe, exLensor response). 1he full expresslon of Lhls reflex
lncluded exLenslon of Lhe greaL Loe and fannlng of Lhe oLher Loes. 1hls ls acLually a
superflclal reflex LhaL ls ellclLed ln Lhe same manner as Lhe planLar response (l.e.,
scraLchlng along Lhe laLeral aspecL of Lhe sole of Lhe fooL and Lhen across Lhe ball of
Lhe fooL Loward Lhe greaL Loe). 1hls ls a prlmlLlve wlLhdrawal Lype response LhaL ls
normal for Lhe flrsL few monLhs of llfe and ls suppressed by suprasplnal acLlvlLy
someLlme before 6 monLhs of age.


uamage Lo Lhe descendlng LracLs from Lhe braln (elLher above Lhe foramen magnum
or ln Lhe splnal cord) promoLes a reLurn of Lhls prlmlLlve proLecLlve reflex, whlle aL
Lhe same Llme abollshlng Lhe normal planLar response. 1he appearance of Lhls reflex
suggesLs Lhe presence of an upper moLor neuron leslon. Chaddock's, Cppenhelm,
Cordon's are all LesLed for when Lhe exLensor response ls equlvocal.

CC8uCn'S SlCn :
Cordon's slgn ls a cllnlcal slgn ln whlch squeezlng Lhe calf muscle ellclLs an exLensor
planLar reflex. lL ls found ln paLlenLs wlLh pyramldal LracL leslons, and ls one of a
number of 8ablnskl- llke responses.

CPAuuCCk'S SlCn:
Chaddock reflex ls a dlagnosLlc reflex slmllar Lo Lhe 8ablnskl reflex. lL ls deslgned Lo
ldenLlfy leslons of Lhe pyramldal LracL, vla sLlmulaLlon of Lhe skln over Lhe laLeral
malleolus leadlng Lo exLenslon of Lhe blg Loe.

lL was ldenLlfled by Charles CllberL Chaddock
Cppenhelm's slgn ls dorslflexlon of Lhe blg Loe ellclLed by lrrlLaLlon downward of Lhe
medlal slde of Lhe Llbla. lL ls named for Permann Cppenhelm.

CLher "8A8lnSkl- LlkL 8LSCnSLS" for Lhe dlsLlncLlon sLudenL

Abnormal reflex seen as exLenslon of Lhe blg Loe
8lng's slgn - mulLlple plnprlcks on Lhe dorsum of Lhe fooL
Cornell's slgn - scraLchlng Lhe dorsum of Lhe fooL
Conda's slgn - flexlng and suddenly releaslng Lhe 4Lh Loe
Monlz slgn - forceful passlve planLar flexlon of Lhe ankle
Schaefer's slgn - squeezlng Lhe Achllles Lendon
SLransky's slgn - vlgorously abducLlng and suddenly releaslng Lhe llLLle Loe
SLrmpell's slgn - paLlenL aLLempLs Lo flex Lhe knee agalnsL reslsLance
1hrockmorLon's reflex - percusslon over Lhe meLaLarsopahalangeal [olnL of Lhe blg
Loe

Abnormal reflex seen as flexlon of Loes
8ekhLerev-Mendel reflex - flexlon of Lhe 2nd Lo 3Lh Loes on percusslon of Lhe
dorsum of Lhe fooL
8ossollmo's slgn - exaggeraLed flexlon of Lhe Loes lnduced by rapld percusslon on
Lhe Llps of Lhe Loes

43) on ULSLS
uear ?ln Llng,

1oday's bedslde class reveal a remarkable lack of knowledge abouL Lhe physlcal slgns
of valvular dlseases. lL ls clear Lo me LhaL Lhe sLudenLs know vL8? llLLle abouL Lhe
examlnaLlon of Lhe pulse.

ulse characLerlsLlcs are ofLen assessed aL Lhe radlal and caroLld arLerles. Powever,
all of Lhe perlpheral pulses should be examlned. alpaLlon of boLh radlal pulses
slmulLaneously may plck up an AorLlc dlssecLlon, and a radlal and femoral pulse
LogeLher wlll help esLabllsh Lhe presence of coarcLaLlon of Lhe aorLa.

1he lnlLlal assessmenL of pulse raLe, volume and characLer ls usually obLalned from
Lhe radlal pulse. 1he pulse ls lovlngly felL wlLh Lhe your lndex and mlddle flngers on
Lhe palmar slde of Lhe wrlsL wlLh your Lhumb on Lhe dorsum of Lhe wrlsL. 8e sure Lo
explaln Lo Lhe paLlenL whaL you are dolng before aLLempLlng Lo palpaLe Lhe femoral
pulse!

8adlo-femoral delay ls classlcally aLLrlbuLed Lo coarcLaLlon of Lhe aorLa, usually due
Lo narrowlng of Lhe aorLa [usL beyond Lhe orlgln of Lhe lefL subclavlan branch. lL ls
more ofLen seen ln young men. SomeLlmes a noLlceably lower pulse volume ln Lhe
femoral arLery compared Lo radlal arLery ls all LhaL ls appreclaLed raLher Lhan Lhe
classlc delay ln Lhe femoral pulse. ln older paLlenLs, radlal femoral delay can
poLenLlally occur due Lo aLherosclerosls and sLlffness beLween Lhe lower llmbs and
upper llmbs arLerles. 1yplcally sLlffer arLerles lead Lo an lncrease ln pulse wave
veloclLy wlLh more rapld propagaLlon of Lhe pulse wave. 1hese paLlenLs also Lend Lo
have hyperLenslon. CoarcLaLlon ls someLlmes dlagnosed ln older adulLs and should
noL be dlsmlssed because of old age.

8aLe
ldeally, CounL Lhe number of beaLs per mlnuLe. lL ls ofLen convenlenL Lo counL Lhe
number of beaLs over 13 seconds and Lhen mulLlply by four. lf Lhe pulse ls slow or
lrregular however, counLlng over a full 60 seconds wlll be more accuraLe. A normal
resLlng hearL raLe ranges beLween 60 and 100 beaLs per mlnuLe.

lL ls a normal for Lhe pulse raLe Lo vary sllghLly wlLh resplraLlon, parLlcularly ln Lhe
young, called slnus arrhyLhmla. 1hls arrhyLhmla ls relaLed Lo dlfferenLlal fllllng of Lhe
lefL and rlghL slde of Lhe hearL and vagal Lone wlLh lnsplraLlon and explraLlon.
1yplcally Lhe hearL raLe lncreases sllghLly durlng lnsplraLlon, and decreases wlLh
explraLlon. As lL ls parLly medlaLed by vagal Lone, Lhls effecL, Lends Lo decllne wlLh
age.

8hyLhm
1he pulse ls regular wlLh slnus rhyLhm (aparL from Lhe caveaL of slnus arrhyLhmla
descrlbed above). A very rapld regular rhyLhm may lndlcaLe slnus, supravenLrlcular
or venLrlcular Lachycardla. An lrregular pulse can be regularly lrregular (a recurrlng
paLLern such as blgemlny or Lype ll hearL block) or lrregularly lrregular (no clear
paLLern, such as aLrlal flbrlllaLlon).

volume
1he volume of Lhe pulse ls besL assessed by palpaLlng one of Lhe larger arLerles such
as Lhe caroLld, brachlal or femoral pulses. lL ls a subLle slgn LhaL requlres experlence
over years for Lhe examlner Lo recognlze low and hlgh volume pulses. A seml-
quanLlLaLlve scale ls used Lo descrlbe pulse volume (lncreased, normal, reduced,
Lhready)

CharacLer
1hls refers Lo an lmpresslon of Lhe pulse waveform derlved durlng palpaLlon.

Some abnormallLles of pulse are descrlbed below.

Anacrot|c pu|se
1hls ls seen ln aorLlc sLenosls, and refers Lo a pulse wave LhaL ls slow rlslng and
generally flaL volume assoclaLed wlLh a low cardlac ouLpuL and prolonged lefL
venLrlcular e[ecLlon Llme. lL suggesLs more severe aorLlc sLenosls.

Co||aps|ng pu|se
1hls ls a slgn of aorLlc regurglLaLlon, alLhough lL ls also seen ln paLlenLs wlLh a
hyperdynamlc clrculaLlon and wlLh a rlgld arLerlal sysLem. A sLlff arLerlal sysLem
leads Lo an accenLuaLed sysLollc peak ln Lhe perlpheral pulses. 1he pulse has an early
peak and Lhen qulckly falls away, glvlng lL a Lapplng quallLy. 1he preferred meLhod ls
Lo palpaLe Lhe radlal pulse wlLh Lhe palm and flngers wrapped around Lhe flexor
aspecL of Lhe wrlsL, and wlLh Lhe arm elevaLed upwards. 1hls accenLuaLes Lhe
Lapplng quallLy of Lhe pulse. 1he collapslng pulse ls also referred Lo as Corrlgans or a
waLer-hammer pulse, afLer a 19Lh cenLury Loy LhaL was a vacuum Lube conLalnlng
waLer or mercury LhaL was fllpped creaLlng a Lapplng or hammer sensaLlon aL Lhe
flngerLlps.

When a collapslng pulse ls deLecLed look for Lhe followlng slgns,

uurozlez slgn: Seen ln severe aorLlc regurglLaLlon. lace Lhe dlaphragm of Lhe
sLeLhoscope over Lhe femoral arLery and press downwards. lnlLlally a sysLollc
murmur wlll be heard. Cradually lncrease pressure over Lhe arLery- a dlasLollc
murmur wlll become evldenL also relaLed Lo Lhe flow reversal wlLh profound aorLlc
regurglLaLlon. now LllL Lhe proxlmal edge of Lhe sLeLhoscope furLher downwards - lf
aorLlc regurglLaLlon ls presenL Lhe sysLollc murmur ls accenLuaLed and Lhe dlasLollc
componenL ls dlmlnlshed. now LllL Lhe dlsLal edge of Lhe sLeLhoscope downwards,
Lhe dlasLollc componenL wlll now be accenLuaLed and Lhe sysLollc reduced. 1hls slgn
has a poslLlve predlcLlve value of close Lo 100 for aorLlc regurglLaLlon, and can
deLecL Lhls leslon ln some paLlenLs ln whom lL ls noL posslble Lo hear Lhe
characLerlsLlc dlasLollc murmur on ausculLaLlon of Lhe hearL.

1raubes slgn: A plsLol shoL" sound heard over Lhe femoral arLery wlLh Lhe ald of a
sLeLhoscope. lL ls necessary Lo compress Lhe femoral arLery dlsLal Lo Lhe sLeLhoscope
head Lo produce Lhe characLerlsLlc double Lone sound.

Pllls slgn: 1hls ls a nonspeclflc slgn of aorLlc regurglLaLlon- lL ls also seen ln oLher
causes of a hyperdynamlc clrculaLlon, such as LhyroLoxlcosls, berl-berl, or pregnancy.
Check Lhe blood pressures ln Lhe upper and lower llmbs. lf Lhe pressure ln Lhe lower
llmbs exceeds LhaL ln Lhe upper llmbs by more Lhan 20 mmPg Lhen Lhe slgn ls
poslLlve.

Culnkes slgn: ulsaLlle blanchlng of Lhe nall bed

ue MusseL's slgn: named afLer Lhe famous lrench poeL whose head nodded ln Llme
wlLh hls arLerlal pulsaLlons due Lo hls syphllls relaLed aorLlc regurglLaLlon.



u|sus paradoxus
1hls ls a mlsnomer. 1hls ls an exaggeraLed physlologlcal phenomenon, raLher Lhan a
paradox as Lhe name lmplles.

1he volume of Lhe pulse rlses wlLh explraLlon wlLh Lhe lncrease ln sLroke volume.
and falls durlng lnsplraLlon. When lL ls presenL, lL suggesLs elLher resLrlcLed lefL
venLrlcular fllllng durlng lnsplraLlon (assoclaLed wlLh a mlld lncreases ln perlcardlal
pressure and lncreased rlghL hearL fllllng LhaL shlfLs Lhe lnLervenLrlcular sepLum
Lowards Lhe lefL venLrlcle Lo lmpalr lefL slded fllllng) such as ln perlcardlal
Lamponade, or exaggeraLed changes ln lnLraLhoraclc pressure as ln severe asLhma..
CLher causes of pulsus paradoxus lnclude rlghL venLrlcular lnfarcLlon, large
pulmonary embolus, and Lense asclLes or obeslLy.

u|sus a|ternans
1hls abnormallLy descrlbes a pulse LhaL alLernaLes beLween a larger and smaller
volume on a beaL Lo beaL basls. 1hls ls a regular pulse and ls seen ln severe cardlac
fallure.

Ierky pu|se
1hls ls ofLen seen ln hyperLrophlc cardlomyopaLhy as Lhe hyperLrophled venLrlcle
rapldly empLles and Lhen qulckly drops lLs ouLpuL as Lhe ouLflow paLhway ls
obsLrucLed.-

44) on IUNC1ICNAL MUkMUkS
uear ?ln Llng,

l Lrled very hard Loday Lo Leach Lhe klddles Lhe approach Lo cardlac examlnaLlon.
MosL lmporLanLly l Lold Lhem LhaL Lhe besL Lhlng Lhey can do Lo lmprove Lhelr
cardlac examlnaLlon Lechnlque ls Lo Lhrow away Lhe sLeLhoscope. 1he ma[orlLy of
Cardlac problems can be dlagnosed from perlpheral slgns wlLhouL Lhe sLeLhoscope.
1he sLeLhoscope conflrms whaL we already know.

Pence l geL lnfurlaLed when Lhe klds rush ln Lo ausculLaLe. nC nC nC! 1haL's Lhe
flnal curLaln call!
lnnocenL sysLollc e[ecLlon murmurs are produced by LurbulenL flow Lhrough Lhe
proxlmal arLerles aL Lhe Llme of venLrlcular e[ecLlon. 1he lnLenslLy of Lhe murmur, as
lnfluenced by sLroke volume or veloclLy of e[ecLlon, and proxlmlLy of Lhe arLerles Lo
Lhe chesL wall deLermlne wheLher Lhe murmur ls audlble wlLh Lhe sLeLhoscope.

1hls LSM Lype murmur Lends Lo peak ln early Lo mldsysLole, usually ends before Lhe
second hearL sound, and ls besL heard on Lhe lefL slde over Lhe mlLral or aorLlc valve
or aL Lhe Lhoraclc lnleL. 1he murmur may be Lhe resulL of LurbulenL flow lnLo Lhe
pulmonary arLery or aorLa, or boLh.

luncLlonal sysLollc murmurs are produced by lncreased veloclLy of blood wlLhln Lhe
cardlovascular sysLem and by exLracardlac facLors. Anemla, fever, hyperLhyroldlsm,
and Lachycardla of any cause may produce funcLlonal murmurs.

uecreased blood vlscoslLy and lncreased veloclLy of blood flow produce Lurbulence.
1he funcLlonal murmur of anemla ls usually of low lnLenslLy and hlgh frequency and
occurs durlng early sysLole Lo mldsysLole. Anemlc murmurs are besL heard over Lhe
mlLral valve or aorLlc valve area.

luncLlonal murmurs may be audlble when sLaLes of hlgh cardlac ouLpuL exlsL. 1he
lncreased cardlac ouLpuL ls produced by boLh Lachycardla and lncreased sLroke
volume.

Some characLerlsLlcs of lnnocenL/luncLlonal Murmurs:
1. SysLollc ln naLure
2. usually shorL ln duraLlon
3. usually sofL
4. usually heard along lefL sLernal edge
3. lnLenslLy varles wlLh phases of resplraLlon and posLure - usually louder when
suplne
6. lnLenslLy louder wlLh exerclse, anxleLy, fever

SLrucLural Leslons whlch may be mlssed:
1here are some sLrucLural leslons whlch glve rlse Lo murmurs closely resembllng an
lnnocenL murmur. 1hese dlfferenLlal dlagnoses musL be borne ln mlnd and efforLs
made Lo exclude Lhem cllnlcally or wlLh Lhe help of lnvesLlgaLlons such as an
elecLrocardlogram (LCC) or chesL x-ray (Cx8).

SLrucLural leslons whlch may be mlssed.

ALrlal SepLal uefecL:
L[ecLlon sysLollc murmur
llxed spllLLlng of 2nd hearL sound
Mld-dlasLollc murmur aL Lrlcuspld area
8lghL bundle branch block

ulmonary valve SLenosls:
L[ecLlon sysLollc murmur
e[ecLlon cllck, aL 2nd lnLercosLal space
Murmur besL heard durlng lnsplraLlon
osL-sLenoLlc dllalaLlon of pulmonary arLery

MlLu AorLlc valve SLenosls:
L[ecLlon sysLollc murmur aL aorLlc area wlLh e[ecLlon cllck
LvP

MlLral valve rolapse:
MldsysLollc murmur aL mlLral area wlLh e[ecLlon cllck

PyperLrophlc CardlomyopaLhy:
lamlly hlsLory
SysLollc murmur aL LSL radlaLlng Lo aorLlc area
Abnormal deep C waves seen
LvP


4S) on VCN kLCkLINGnAUSLN
uear ?ln Llng,

l always have dlfflculLy rememberlng Lhe chromosomes lnvolved

"neuroflbromaLosls 1ype l" = "von 8eckllnghausen has exacLly 17 alphabeLs!" =
Chromosome 17
"neuroflbromaLosls 1ype ll" = "1ype 2 = 22" = Chromosome 22

46) on WILSCN'S DISLASL
uear ?ln Llng,

1o help you remember an uncommon condlLlon commonly seen ln exams.....

Wllson's dlsease : A8Cu

A - AsLerlxls
8 - 8asal ganglla degeneraLlon
C - Copper accumulaLlon wlLh reduced Ceruloplasmln level, causlng Cornea deposlLs
(kayser-llelscher rlngs), Chorelform movemenLs, psyChlaLrlc abnormallLles, llver
Clrrhosls and LreaLmenL ls wlLh ChelaLlon.
u - uemenLla


47) on CCULCMC1Ck NLkVL
My dear yln llng,

Cranlal nerves lll, lv and vl are usually LesLed LogeLher. ?ou lnsLrucL Lhe paLlenL Lo
hold hls head sLlll and follow only wlLh Lhe eyes your flnger or penllghL LhaL
clrcumscrlbes a large "P" ln fronL of Lhe paLlenL. Cr you place your hand on hls head
Lo lmmoblllse lL for oLher Lhan Lhe abnormal medlcal person, any normal person wlll
Lurn hls head when asked Lo follow Lhe flnger!

Slnce Lhe oculomoLor nerve conLrols mosL of Lhe eye muscles, damage Lo Lhls nerve
ls also known by Lhe down n' ouL slgns, because of Lhe poslLlon of Lhe affecLed eye.

uplllary reflex
1he oculomoLor nerve also conLrols Lhe consLrlcLlon of Lhe puplls. 1hls can be LesLed
ln Lwo maln ways. 8y movlng a flnger rapldly Lowards a person's face Lo lnduce
accommodaLlon, Lhelr puplls should consLrlcL.

Shlnlng a llghL lnLo Lhelr eyes from Lhe slde wlll make Lhelr puplls consLrlcL. uo noL
shlne from dlrecLly ln fronL for any normal human wlll look aL Lhe llghL hence have
accommodaLlon reflex! 8oLh puplls should consLrlcL aL Lhe same Llme, lndependenL
of whaL eye Lhe llghL ls acLually shone on. l Lell my sLudenLs a hundred Llmes Lo
8emember Lo approach from Lhe slde as Lhe paLlenL WlLL focus on Lhe penllghL lf
you approach from hls fronL and hence lnlLlaLe accommodaLlon and assoclaLed
puplllary consLrlcLlon, yeL when l examlne Lhem, Lhey wlll nonchalanLly shlne from
Lhe fronL. epLlc ulcer dlsease!

Argyll-8oberLson pupll (Aka "rosLlLuLe's pupll" - A prosLlLuLe AccommodaLes, buL
does noL reacL )
AccommodaLlon reflex presenL, uplllary reflex absenL

1he oculomoLor nerve arlses from Lhe anLerlor aspecL of mldbraln. 1here are Lwo
nuclel for Lhe oculomoLor nerve:

1he oculomoLor nucleus orlglnaLes aL Lhe level of Lhe superlor colllculus. 1he
muscles lL conLrols are Lhe clllary muscle (affecLlng accommodaLlon ), and all
exLraocular muscles excepL for Lhe superlor obllque muscle and Lhe laLeral recLus
muscle.
1he Ldlnger-WesLphal nucleus supplles parasympaLheLlc flbres Lo Lhe eye vla Lhe
clllary gangllon, and Lhus conLrols pupll consLrlcLlon. When Lhese flbres are
damaged, Lhe dellcaLe sympaLheLlc- parasympaLheLlc balance whlch malnLalns our
puplllary slze ls upseL and unopposed sympaLheLlc drlve causes a dllaLed pupll.

47) on S1UM ALNDICI1LS
uear ?ln Llng,

A male paLlenL comes wlLh fever, loss of appeLlLe and 8ll paln. Pe has pasL hlsLory of
appendlcecLomy 3 years ago. Cn examlnaLlon Lhere ls Lenderness and mlld guardlng
ln Lhe 8ll.

WhaL are your LhoughLs?

uo you know appendlclLls can re occur even afLer appendecLomy ?

SLump appendlclLls, alLhough rare, ls a real enLlLy LhaL ls ofLen noL consldered durlng
Lhe evaluaLlon of paLlenLs wlLh rlghL lower quadranL paln and a surglcal hlsLory of
appendecLomy. 1he hlsLory of appendecLomy may delay Lhe dlagnosls and
managemenL of Lhls enLlLy by mlsleadlng Lhe physlclan lnLo Lhlnklng LhaL Lhls paLlenL
could never have appendlclLls agaln. Powever, Lhe dlagnosls of appendlclLls should
be consldered ln any paLlenL wlLh rlghL lower quadranL paln, even lf Lhere ls a
hlsLory of appendecLomy.

SLump appendlclLls ls Lhe re-lnflammaLlon of any resldual appendlceal Llssue afLer an
appendecLomy. Slnce Lhe lnlLlal reporLs of sLump appendlclLls, lL remalns a rare
condlLlon, lL occurs when Lhere has been an lncompleLe appendecLomy . CompleLe
removal of Lhe appendlx ls essenLlal ln prevenLlng Lhe occurrence of Lhls condlLlon.
Many reporLs have suggesLed LhaL sLump appendlclLls resulLs from a sLump LhaL ls
lefL Loo long. lL has been suggesLed LhaL wlLh Lhe wldespread use of laparoscoplc
Lechnlque, Lhere mlghL be an lncrease ln Lhe lncldence of sLump appendlclLls, buL
sLump appendlclLls has been reporLed Lo occur afLer elLher laparoscoplc or open
appendecLomy. 1herefore, Lhe relaLlonshlp beLween laparoscoplc appendecLomy
and sLump appendlclLls ls noL proven.

Cne dlsadvanLage of laparoscoplc appendecLomy ls Lhe lnablllLy Lo feel sLrucLures
and [udge paLhology by palpaLlon. ulfflculLy ln reLracLlng Lhe long appendlx may be
responslble for Lhe long appendlceal sLump LhaL may occur wlLh laparoscoplc
appendecLomy. 1he lncldence of sLump appendlclLls ls also probably
underesLlmaLed and under-reporLed.


48) on Grave's d|sease
uear ?ln Llng,

Crave's dlsease ls deflned by Lhe Lhree feaLures of Lye lnvolvemenL, Acropachy and
occaslonally re Llblal myxodema on Lop of Lhe PyperLhyroldlsm. SomeLlmes Lhe eye
lnvolvemenL precedes Lhe hyperLhyroldlsm. 1hey presenL as double vlslon,
chemosls, proLruslon, eLc. 1o help you remember, pls recall
nC SLCS ls Lhe mnemonlc used for Lhe cllnlcal progresslon of Craves'
opLhalmopaLhy.

n: no slgns or sympLoms
C: Cnly slgns l.e. lld lag and lld reLracLlon
S: SofL Llssue lnvolvemenL (con[uncLlvlLls, chemosls, and perlorblLal edema)
: ropLosls
L: LxLraocular muscles lnvolved, commonly lnferlor recLus resulLlng ln dlplopla when
looklng up
C: Corneal lnvolvemenL (drylng and ulceraLlon due Lo Lhe lnablllLy Lo close Lhe eye
llds)
S: SlghL loss.


49) on kena| Ia||ure
uear ?ln Llng,

are you aware LhaL Lhe humble SLarfrulL ls a klller!?

SLar frulL, belonglng Lo Lhe Cxalldaceae famlly, specles Averrhoa carambola, ls a
popular frulL among CrlenLals. 1here have been reporLs of hlccup, confuslon, and
occaslonal faLal ouLcomes ln uraemlc paLlenLs afLer lngesLlon of sLar frulL.

An exclLaLory neuroLoxln from sLar frulL has been lmpllcaLed alLhough Lhe exacL
naLure of Lhls Loxlc subsLance has noL been ldenLlfled. 8enal fallure paLlenLs can
have sympLoms lncludlng hlccup, confuslon, vomlLlng, lmpalred consclousness,
muscle LwlLchlng and hyperkalaemla shorLly afLer lngesLlon of sLar frulL.

SympLoms of mosL paLlenLs can be resolved wlLh dlalysls or sponLaneously. 1he
close Lemporal relaLlonshlp of lngesLlon of sLar frulL and onseL of sympLoms sLrongly
suggesLs Lhe exlsLence of a causal relaLlonshlp beLween Lhe Lwo.

lL ls recommended LhaL uraemlc paLlenLs should LoLally absLaln from sLar frulL due Lo
Lhese poLenLlally faLal compllcaLlons.

S0) on ara|ys|s
uear ?ln Llng,
a paLlenL presenLlng well and Lhe afLer a whlle suddenly plops down ln severe
weakness and leLhargy ls dramaLlc and frlghLenlng. A condlLlon LhaL we suspecL ls
Pypokalaemla.
1he hypokalemlc paralysls lnclude a group of dlsorders wlLh dlfferlng eLlologles buL a
common presenLaLlon.
lamlllal hypokalemlc paralysls (lP) ls a geneLlc channelopaLhy, wlLh an auLosomal
domlnanL paLLern of lnherlLance. 1hankfully noL common.
1hyroLoxlc hypokalemlc perlodlc paralysls (1P) ls an acqulred dlsorder LhaL can
presenL ln a very slmllar manner Lo lP when cllnlcal feaLures of hyperLhyroldlsm
are sub-cllnlcal, as Lhey commonly are. 1reaLmenL of hyperLhyroldlsm prevenLs
1P, Lhough Lhe degree of hyperLhyroldlsm does noL predlcL Lhe degree of
paralysls.
aLlenLs ofLen have no oLher sympLoms of hyperLhyroldlsm durlng aLLacks.
1hankfully Lhe paLlenLs l had seen all had obvlous Crave's dlsease so lL was noL Loo
dlfflculL Lo dlagnose.
1hyroLoxlc hypokalemlc perlodlc paralysls ls llkely due Lo excesslve Lhyrold-
hormone-lnduced adrenerglc sLlmulaLlon of Lhe sodlum-poLasslum (na+-k+) pump,
whlch drlves poLasslum lnLo cells.
oLasslum levels are normal beLween aLLacks, and Lhere ls no decrease ln LoLal body
poLasslum. ALLacks of paralysls are classlcally preclplLaLed by an lnsulln surge afLer a
hlgh carbohydraLe meal, or lncreased adrenerglc acLlvlLy wlLh physlcal exerLlon.
Powever, oLher physlologlc sLressors such as sepsls, Lrauma, hypoLhermla, menses,
and emoLlonal sLress are known Lrlggers of 1P.
Lplsodes are acuLe ln onseL and ofLen occur ln Lhe nlghLLlme or mornlng followlng a
day of sLrenuous exerclse. aLlenLs may also descrlbe a prodrome of muscle aches or
cramps ln Lhe days precedlng an acuLe eplsode.
1he paLlenL may noL have sympLoms of overL hyperLhyroldlsm, so Lhyrold funcLlon
LesLs should be checked ln all paLlenLs wlLh hypokalemlc paralysls. 1he LkC wlll
demonsLraLe flndlngs Lyplcal of hypokalemla.
1he hypokalemla of 1P affecLs Lhe sLrlaLed/skeleLal muscles, noL Lhe nerves or Lhe
smooLh muscle. roxlmal muscles and Lhose of Lhe lower exLremlLles are more
severely affecLed, usually, buL noL always, ln a symmeLrlcal paLLern, paLlenLs may
have elLher hemlplegla or paraplegla. Muscles of resplraLlon are Lyplcally spared, buL
cases of resplraLory fallure have been reporLed. MenLal sLaLus and sensaLlon are
unaffecLed.
ln paLlenLs wlLh 1P, hypokalemla ls ofLen exacerbaLed by assoclaLed
hypophosphaLemla and mlld hypomagnesemla. 1ransporL of phosphorus across cell
membranes occurs wlLh LhaL of poLasslum.
1hyroLoxlc hypokalemlc perlodlc paralysls ls 20 Lo 40 Llmes more common ln
hyperLhyrold males Lhan ln hyperLhyrold females, and occurs ln up Lo 13 of
hyperLhyrold Aslan males. All Lhe paLlenLs l had seen were Males.
AdmlnlsLerlng poLasslum durlng an aLLack can rapldly aborL Lhe eplsode. Powever,
Lhls should be done cauLlously glven Lhe LranslenL naLure of Lhe Lranscellular shlfL, as
Lhere ls a rlsk of posL-LreaLmenL hyperkalemla ln up Lo 40 of paLlenLs. Cardlac
arresL due Lo rebound hyperkalemla has been reporLed. lurLhermore, sponLaneous
recovery of flaccld paralysls suggesLs LhaL poLasslum can shlfL back ouL of Lhe cell
wlLhouL supplemenLaLlon.
nonselecLlve beLa-blockers such as propanolol ls used Lo lnhlblL adrenerglc
sLlmulaLlon of Lhe na+-k+ pump. (8emember LhaL Pyperkaleamla ls a
conLralndlcaLlon for Lhe use of propanolol!) WlLh adequaLe suppresslon of
adrenerglc acLlvlLy, as lndlcaLed by reduced hearL raLe, lncreases ln serum poLasslum
and rapld lmprovemenL of paralysls can be seen. 1hls may ellmlnaLe Lhe need for
supplemenLal poLasslum. aLlenLs wlLh more severe or rapldly progresslve paralysls,
or wlLh cardlac conducLlon abnormallLles conslsLenL wlLh hypokalemla, should be
LreaLed wlLh poLasslum.
revenLlon of acuLe eplsodes depends prlmarlly on malnLenance of a euLhyrold
sLaLe. nonselecLlve beLa-blockers are also effecLlve. oLasslum supplemenLs can be
prescrlbed Lo be Laken ln case paLlenLs have an acuLe recurrenL eplsode desplLe
Lhese measures.
Powever, because poLasslum levels are normal beLween aLLacks, Lhere ls no role for
rouLlne poLasslum supplemenLaLlon or poLasslum-sparlng dlureLlcs.
ManagemenL of 1P should lnclude supporLlve care, wlLh parLlcular concern for
resplraLory sLaLus, and monlLorlng of serum elecLrolyLes. Serlal measuremenL of Lhe
lvC can glve early warnlng LhaL Lhe paLlenL may need resplraLory supporL.
CharacLerlsLlcs whlch would favor lP over 1P lnclude a famlly hlsLory of
hypokalemlc paralysls, Caucaslan eLhnlclLy, and female sex.
ulfferenLlaLlon beLween lP and 1P ls crlLlcal because LreaLmenL dlffers. lamlllal
hypokalemlc paralysls requlres a more vlgorous poLasslum repleLlon, whlle 1P
may be LreaLed more conservaLlvely, someLlmes solely wlLh observaLlon or
propranolol.


S1) on Assoc|at|ons
uear ?ln Llng,

8ralnsLem answers now!

When see|ng nausea + t|redness+ hyperp|gmentat|on =?

addlsonlan crlsls

We|ght |oss + Amenorrhea + fa|||ng ha|r=?

LhyroLoxlcosls

Syncope + ang|na+dyspnoea = ?

SAu ls Lhe sympLoms of whaL?

Lhls ls a classlc Lrlad!!!

aorLlc sLenosls

we|ght |oss + ma|a|se + fever + prur|tus=??

lymphoma

and Lhe name of Lhe fever????

pel ebsLeln fever

Cant see, cant pee, cant c||mb a tree=??

relLer's dlsease

abd pa|n + [aund|ce + fever=???

ascendlng cholanglLls

S causes of Iever, Ch|||s and k|gours???

lobar pneumonla, abscess, pyelonephrlLls, malarla, ascendlng cholanglLls
oLhers lnclude SepLlcaemla, lnfluenza, uengue

G|ve me S causes of LSk >100

18, MulLlple myeloma, M8, C1u,
Auvance Mallgnancles esp wlLh araneoplasLlc syndromes
SepLlcaemla

S2) on er|phera| Arter|a| D|sease
uear ?ln Llng,

SlgnlflcanL proporLlons of paLlenLs do noL have classlcal feaLures of lnLermlLLenL
claudlcaLlon and Lherefore Au ls an under-dlagnosed condlLlon. My sLudenLs love
Lo ask abouL calf paln and paln before how many "blocks", Lhls as you know ls uLLerly
unrellable!

Cllnlcal examlnaLlon ls lmporLanL Lo declde whlch paLlenLs should undergo furLher
assessmenL, and palpaLlon of Lhe perlpheral pulses ls lmporLanL. Any palpable pulse
abnormallLy (absenL or reduced femoral, popllLeal, dorsalls pedls, or posLerlor Llblal
arLerles) lncreases Lhe llkellhood of Au and Lhe absence of any palpable pulse
abnormallLy decreases Lhe llkellhood of Au.
Powever, assesslng paLency of Lhe popllLeal arLery ls noL always posslble by
palpaLlon. 1hls ls due Lo a comblnaLlon of deep placemenL of Lhe arLery ln Lhe
popllLeal fossa and Lhe presence of conslderable quanLlLy of faL boLh behlnd Lhe
arLery and ln Lhe superflclal Llssues.

Cne Lechnlque LesLed ln CSCLs ls uslng Lhe flexlon of Lhe knees Lo faclllLaLe
relaxaLlon of Lhe gasLrocnemlus maklng lL more accesslble Lo palpaLlon. ln a paLlenL
wlLh paLenL popllLeal arLery, Lhe Lo and fro pulsaLlle movemenL of Lhe fooL (ln
con[uncLlon wlLh hearL beaL) wlll be observed when he slLs ln a hlgh chalr wlLh legs
crossed such LhaL Lhe popllLeal fossa of Lhe leg belng examlned lles over Lhe knee of
Lhe opposlLe leg. 1he paLlenL musL slL on a hlgh chalr so LhaL Lhe popllLeal fossa lles
agalnsL Lhe knee cap of Lhe opposlLe leg. 1he Lop leg should be compleLely relaxed
so Lhe welghL of Lhe leg compresses Lhe arLery beLween Lhe knee cap of Lhe lower
leg and Lhe proxlmal parL of Lhe Llbla

1hls ls called Lhe "Cross leg LesL" or "luschlg's LesL"



S3) Cn nypothyro|d|sm and vague symptoms
uear yln llng,
aL every bedslde class, l beg my sLudenLs Lo always Lhlnk of PypoLhyroldlsm across a
wlde range of complalnLs from ACS to deafness to |oss of memory to prur|tus.

ls always Lhlnk of lL Loo ln paLlenLs wlLh muscle weakness or LnLA8CLu muscles!!

PypoLhyrold myopaLhy Lyplcally manlfesLs as polymyoslLls-llke myopaLhy wlLh
proxlmal muscle weakness and an lncreased creaLlne klnase level. Powever, lL
someLlmes manlfesLs as muscle enlargemenL (pseudohyperLrophy), ln adulLs, Lhls
condlLlon ls called Poffman syndrome. ln chlldren wlLh hypoLhyrold dlsease
(creLlnlsm), a paLLern of proxlmal weakness and dlffuse muscle enlargemenL ls also
seen. ls also noLe LhaL hypoLhyroldlsm ls LhoughL Lo predlspose lndlvlduals Lo
rhabdomyolysls Loo.

1here ls an lnverse correlaLlon beLween Lhyrold funcLlon and Ck levels: ln
hypoLhyrold paLlenLs, Ck levels were elevaLed, whlle ln hyperLhyrold paLlenLs, Ck
levels were lower Lhan normal. AfLer LreaLmenL Lo resLore normal Lhyrold funcLlon,
Ck levels reLurned Lo normal.

1hree ouL of four paLlenLs wlLh hyperLhyroldlsm experlenced muscle cramps durlng
LreaLmenL Lo rapldly reduce Lhyrold funcLlon Lo normal levels.

Serum creaLlnlne klnase ls decreased ln LhyroLoxlcosls buL lncreased ln
hypoLhyroldlsm. rof khalld has a publlcaLlon on Lhe sub[ecL ln 1998 when he
publlshed abouL Lhese subLle changes seen ln subcllnlcal hyper and hypoLhyroldlsm
and hence quesLloned wheLher we should LreaL low 1SP or hlgh 1SP when 14 or 13
are ln Lhe normal range.
1he S|gn of nertoghe or ueen Anne's s|gn ls a Lhlnnlng or loss of Lhe ouLer Lhlrd of
Lhe eyebrows, and ls a slgn of hypoLhyroldlsm.


rofessor khalld kadlr





S3) on MLN
uear ?ln Llng,

|ease do NC1 proceed |f you are under 21.

l always had dlfflculLy rememberlng MLn 1 and 2. Lucklly l am noL Lhe one slLLlng for
exams! 1hls was unLll l was LaughL Lhls!!

1here are 2 klnds of MLn ln Lhls world

MLn 1ype 1, are sLralghL guys, and Lhey only Lhlnk abouL ussy, ussy, ussy!
So Lhey have mallgnancles of Lhe

ancreaLlc
araLhyrold
lLulLary.

MLn 1ype 2, are gay guys, and all Lhey Lhlnk abouL ls Anus, enls, and 1esLlcles!
So Lhey have mallgnancles of Lhe

Adrenals
araLhyrold
1hyrold.
And Lhere you have lL, boLh Lypes of MulLlple Lndocrlne neoplasla... l mean, boLh
Lypes of MLn!


S4) on Coarctat|on
uear ?ln Llng,

WhaL ls uock's slgn?

8llaLeral rlb noLchlng seen ln Cx8 ln CoarcLaLlon of Lhe AorLa ls known as uock's slgn,
correspondlng Lo Lhe collaLeral clrculaLlon of Lhe lnLernal mammary arLerles Lyplcally
aL rlbs 3-8.
lnferlor 8lb noLchlng ls usually due Lo enlargemenL of Lhe neurovascular bundle.
Conslder Lhe followlng maln causes:

CoarcLaLlon of Lhe AorLa
lalloL's LeLralogy - unllaLeral lefL followlng 8lalock-1ausslg shunL (lefL subclavlan
arLery anasLamosed Lo lefL pulmonary arLery - collaLeral clrculaLlon vla rlbs Lo supply
arm)
neuroflbromaLosls (more classlcally wavy 'rlbbon rlbs')
LongsLandlng SvC obsLrucLlon (venous collaLerals)

CoarcLaLlon of Lhe AorLa ls classlfled lnLo 2 Lypes
Locallsed (AdulL) MosL common Lype. ShorL narrowlng close Lo llgamenLum
arLerlosum. Cardlac anomalles uncommon.
1ubular hypoplasla (lnfanLlle). Long segmenL sLenosls. Cardlac anomalles common.



SS) on u|monary Lmbo||sm
uear ?ln Llng,

undlagnosed L has a hosplLal morLallLy raLe as hlgh as 30, whlch falls Lo abouL 8
lf L ls dlagnosed and LreaLed approprlaLely

1he dlagnosls of L remalns one of Lhe mosL dlfflculL problems confronLlng
cllnlclans. L ls consldered ln Lhe dlfferenLlal dlagnosls of many cllnlcal
presenLaLlons, lncludlng chesL paln, hemopLysls, and dyspnea. ?eL less Lhan 33 of
paLlenLs suspecLed of havlng L acLually have L

ln paLlenLs wlLh ulmonary embollsm, pleurlLlc chesL paln and haemopLysls lndlcaLes
LhaL ulmonary lnfarcLlon had occurred.

Cnly abouL 1 ln 10 paLlenLs wlLh ulmonary embollsm develop lnLo pulmonary
lnfarcLlon!

Sudden onseL of dyspnoea, vague chesL paln, llghL headedness are Lhe mosL
common sympLoms of L. 1he ma[orlLy of paLlenLs have no slgns oLher Lhan
Lachypnoea and Lachycardla, whlle exLenslve embollsm wlll resulL ln cyanosls,
lncreased !v, hypoLenslon.

ulmonary lnfarcLlon wlll resulL ln haemopLysls, leural rub, lLvL8, dullness and
crepLs over Lhe lnfarcLed area and someLlmes pleural effuslon.

|e remember that recurrent sma|| L |s a cause of UC.

Pemodynamlc decompensaLlon occurs noL only because of physlcal obsLrucLlon of
blood flow buL also because of Lhe release of humoral facLors, such as seroLonln
from plaLeleLs, Lhrombln from plasma, and hlsLamlne from Llssue.

AcuLe L lncreases pulmonary vascular reslsLance, parLly aLLrlbuLable Lo hypoxlc
vasoconsLrlcLlon. ln paLlenLs wlLhouL prlor cardlopulmonary dlsease, Lhe mean
pulmonary arLery pressure can double Lo approxlmaLely 40 mm Pg.

ls noLe LhaL no A8C daLa had sufflclenL negaLlve predlcLlve value. A normal A8C
does nC1 exclude L. Pypoxaemla seems Lo be a rellable slgn of pulmonary
embollsm, a pC2 of under 30 mm Pg was always assoclaLed wlLh a severe embollsm
wlLh ampuLaLlon of over 40 of Lhe pulmonary vascular bed. 1he fallure of
supplemenLal oxygen Lo correcL arLerlal hypoxemla accompanylng acuLe L ofLen
reflecLs Lhe exlsLence of rlghL Lo lefL shunLlng of venous blood Lhrough Lhe hearL, Lhe
lungs, or boLh.
8esplraLory alkalosls ls commonly seen

1here ls 8lghL-Lo-lefL shunLlng: no venLllaLlon and venous blood enLers sysLemlc
clrculaLlon. lncreased anaLomlc dead space: breaLhed gas does noL enLer gas
exchange unlLs of Lhe lung

A neg u ulmer serves only Lo exclude and a poslLlve resulL cannoL conflrm.

Wells' 1wo-level L Score helps ln declslon maklng


nampton's hump |ong arrow: Lhe wedge-shaped opaclLy aL Lhe perlpheral lefL lung
fleld
a||a's s|gn short arrow: enlargemenL of Lhe 8lghL descendlng pulmonary arLery


Westermark's s|gn: Lhe area of hypoperfuslon dlsLal Lo Lhe rlghL pulmonary
vasculaLure. 1hls represenLs a probable pulmonary embollsm.



S6) on ked Meat
uear ?ln Llng,

"1he gouLy arLhrlLls paLlenL was advlsed nC1 Lo eaL red meaL"

'Why?' l ask? 'WP????'

Why some meaLs - noL [usL pork or chlcken - are llghLer or darker ls a falrly
compllcaLed sub[ecL. Several facLors conLrlbuLe Lo Lhe colour of meaL. Why ls your
sLlrred frled horr funn's beef dark ln colour le red meaL?
Paemoglobln, ls absorbed ln muscle, conLrlbuLes a blL of red colour. Muscles LhaL
are heavlly used may noL be able Lo geL enough oxygen from Lhe blood, and musL
resorL Lo oxygen sLored ln myoglobln molecules.
8oLh haemoglobln and myoglobln are red when carrylng oxygen. uependlng on how
much use Lhe muscle sees, Lhere ls more need of Lhe oxygen sLored ln myoglobln,
and wlll be darker as a resulL.

1urkeys for example, whlch sLand around a loL and hardly ever fly, have dark leg
meaL buL breasLs LhaL are whlLe.
Came anlmals, whlch Lend Lo use all Lhelr muscles, are essenLlally all dark meaL,
whlle domesLlcaLed anlmals generally have a mlx of boLh llghL and dark.

ln Lerms of cooklng, dark meaL generally has more flavour, buL, because Lhose
muscles were more acLlvely exerclsed, Lends Lo be Lougher. LlghLer meaLs Lend Lo be
more Lender buL have less flavour. now you know why some meaLs are Lender and
some Lough.

uleLs whlch are hlgh ln purlnes and hlgh ln proLeln have long been lncrlmlnaLed of
causlng an lncreased rlsk of gouL. Plgh urlc acld levels assoclaLed wlLh gouL derlve
largely from foods rlch ln proLeln and purlne, whlch produce urlc acld as a wasLe
producL

eople who consumed Lhe hlghesL amounL of meaL were 40 percenL more llkely Lo
have gouL Lhan Lhose who aLe Lhe leasL amounL of meaL.
eople who aLe Lhe mosL seafood were 30 percenL more llkely Lo have gouL.

CbeslLy can be llnked Lo hlgh urlc acld levels ln Lhe blood. eople who are
overwelghL should go on a reasonable welghL-loss program. lasLlng or severe
dleLlng can acLually ralse urlc acld levels and cause gouL Lo worsen.
usually people can eaL whaL Lhey llke wlLhln llmlLs.

eople who have kldney sLones due Lo urlc acld, gouLy Lophl, chronlc Lophaceous
gouL may need Lo acLually ellmlnaLe purlne-rlch foods from Lhelr dleL because Lhose
foods can ralse Lhelr urlc acld level.
Consumlng coffee and Lea ls noL a problem buL alcohol can ralse urlc acld levels and
provoke an eplsode of gouL. urlnklng aL leasL 10-12 elghL-ounce glasses of non-
alcohollc flulds every day ls recommended, especlally for people wlLh kldney sLones.

S7) Cn redn|so|one
uear ?ln Llng,

rednlsolone can have unlque slde effecLs well known Lo us all.
Among Lhe mosL memorable ones are

ancreaLlLls
Avascular necrosls of Lhe head of Lhe femur
osLerlor sub capsular caLaracL
LxLenslve acne
lnLracranlal P1
aplllodema
sychosls
Claucoma

l remember Lhese well because rof llorence Wang LaughL me Lhls. She was runnlng
Lhe Lupus cllnlc ln uP and used a loL of prednlsolone.


S8) Cn I13
uear ?ln Llng,

WhaL ls Lhls 13 LhaL we see ln our Lhyrold funcLlon LesLs?
Pow do we lnLerpreLe lL?
When ls lL useful?


18l-lCuC1P?8CnlnL (13) 1here are Lwo assays avallable, one measures LoLal 13 and
Lhe oLher free 13. 1he LoLal 13 comprlses of boLh proLeln bound and free 13. 1he
free componenL ls Lhe acLlve form and comprlses a mere 0.3 of LoLal clrculaLlng 13.

13 ls Lhe blologlcally acLlve Lhyrold hormone, possesslng 3 Llmes Lhe meLabollc
power of 14. ln man some 80 of 13 ls produced from 14 by converslon ln llver and
kldney. 1herefore llLLle ls produced ln Lhe Lhyrold lLself.

1he converslon of 14 Lo 13 can depend on a number of slLuaLlons such as chronlc
lllness or surglcal sLress whlch cause a fall ln 14 Lo 13 converslon (called low 13
syndrome). Pence l14 may be normal and Lhe paLlenL ls hypoLhyrold!

SLarvaLlon also alLers 14 Lo 13 converslon wlLh a fall ln 13 as Lhe body Lrles Lo reduce
lLs meLabollsm Lo conserve energy. 1hls ls survlval adapLaLlon.
MeasuremenL of f13 ln paLlenLs wlLh suspecLed hyperLhyroldlsm ls rarely lndlcaLed.
1hls ls reserved for slLuaLlons where hyperLhyroldlsm ls suspecLed cllnlcally and 1SP
ls suppressed, buL Lhe f14 ls noL elevaLed. f13 lf elevaLed Lells us LhaL 13
LhyroLoxlcosls ls presenL.

MeasuremenL of f13 ls noL lndlcaLed ln hypoLhyroldlsm.
ln hyperLhyroldlsm, boLh Lhyroxlne 14 and 13 levels (LoLal and free) are usually
elevaLed. 1reaLmenL and monlLorlng can be done wlLh l14 buL lf l14 ls normallsed
wlLh LreaLmenL and paLlenLs sLlll appear hyperLhyrold Lhen l13 should be measured.
ls noLe LhaL Lhe suppressed 1SP Lakes Llme Lo recover and hence ls noL helpful
lnlLlally.

l13 levels may be requlred Lo evaluaLe cllnlcally euLhyrold paLlenLs who have an
alLered dlsLrlbuLlon of blndlng proLelns (eg, pregnancy, dysalbumlnemla).
8Lw pls do noL dlagnose subcllnlcal Lhyrold dysfuncLlon unless you are sure LhaL Lhe
followlng ls fulfllled.

1he followlng flve crlLerla deflne endogenous subcllnlcal Lhyrold dysfuncLlon:

a. 1SP lncreased above, or decreased below deslgnaLed llmlLs
b. normal free 14 concenLraLlon and free 13
c. 1he abnormallLy ls noL due Lo medlcaLlon
d. 1here ls no concurrenL crlLlcal lllness or plLulLary dysfuncLlon.
e. A susLalned abnormallLy ls demonsLraLed over 3-6 monLhs.
1herefore ln summary

MeasuremenL of serum 13 ls lndlcaLed, as follows:

a. ln suspecLed hyperLhyroldlsm wlLh suppressed 1SP and normal serum 14, Lo
ldenLlfy 13-LhyroLoxlcosls and dlsLlngulsh Lhls enLlLy from subcllnlcal LhyroLoxlcosls.
b. uurlng anLlLhyrold drug Lherapy Lo ldenLlfy perslsLenL 13 excess, desplLe normal
or low serum 14 values.
c. lor dlagnosls of amlodarone-lnduced hyperLhyroldlsm, whlch should noL be based
on 14 excess alone because of Lhe frequency of euLhyrold hyperLhyroxlnemla durlng
amlodarone LreaLmenL.
d. 1o assess Lhe exLenL of 13 excess ln lndlvlduals LreaLed wlLh Lhyrold exLracLs of
anlmal orlgln, our slnsehs uae monkey Lhyrold drled and grounded! And Lo assess a
poLenLlally damaglng hormone excess LhaL ls noL reflecLed by Lhe level of 14.
e. 1o ldenLlfy 13-predomlnanL LhyroLoxlcosls, an enLlLy LhaL ls less llkely Lo achleve
remlsslon.
f. 1o deLecL early recurrence of hyperLhyroldlsm afLer cessaLlon of anLlLhyrold drug
Lherapy.
h. 1o esLabllsh Lhe exLenL of 13 excess durlng hlgh-dose replacemenL or suppresslve
Lherapy wlLh 14, or afLer an accldenLal or lnLenLlonal 14 overdose.

Low serum 13 concenLraLlons have llLLle speclflclLy or senslLlvlLy for Lhe dlagnosls of
hypoLhyroldlsm. Many paLlenLs wlLh nonLhyroldal lllness have low values, and Lhe
serum 13 concenLraLlon can remaln ln Lhe reference range unLll hypoLhyroldlsm ls
severe.



S9) on Ca|c|f|cat|ons |n Ckk
uear ?ln Llng,

1hls Cx8 shows lnnumerable small, puncLaLe calclflcaLlons LhroughouL boLh lungs.
no dlfflculLy for you. WhaL are Lhe dlfferenLlal dlagnosls?



CalclflcaLlon ln a pulmonary nodule (n) on lmaglng lndlcaLes a hlgh probablllLy LhaL
Lhe leslon ls benlgn. 8uL noL all calclfled n are benlgn and Lhe dlfferenLlal
conslderaLlons lnclude a prlmary cenLral lung carclnold, meLasLasls and a prlmary
bronchogenlc carclnoma.

8adlologlcal demonsLraLlon of calclflcaLlon ln lung cancers ls uncommon buL when
encounLered may lead Lo mlsdlagnosls. Amorphous, puncLaLe, and reLlcular paLLerns
of calclflcaLlon have been descrlbed ln lung cancer. MallgnanL Lumors may engulf a
pre-exlsLlng granuloma.
1he prevalence of calclfled lung cancers ldenLlfled on convenLlonal chesL
radlographs ls sald Lo be 1. MallgnanL nodules may mlmlc Lhe appearances of
benlgn calclfled granulomas, Lyplcal examples are meLasLases from osLeogenlc
sarcoma or chondrosarcoma.

ulfferenLlal dlagnosls of dlffusely dlsLrlbuLed small calclfled nodules lncludes
lnfecLlons, lung meLasLases, chronlc pulmonary hemorrhage, pneumoconlosls,
deposlLlon dlseases and ldlopaLhlc dlsorders such as pulmonary alveolar
mlcrollLhlasls.

osL Chlcken pox pneumonla
Chlcken pox pneumonla may cause Llny wldespread mlcronodular calclflcaLlon wlLh
nodules 1-3 mm ln dlameLer as a laLe sequela. 1here ls no assoclaLed calclflcaLlon of
medlasLlnal lymph nodes.

18
PlsLoplasmosls
uysLrophlc calclflcaLlon follows caseaLlon, necrosls or flbrosls. Calclfled nodules
followlng lnfecLlons are well deflned and ofLen measure 2-3 mm ln dlameLer. Such
nodules ofLen follow healed dlssemlnaLed hlsLoplasmosls and rarely may follow
healed mlllary Luberculosls. When secondary Lo Luberculosls or hlsLoplasmosls,
Lhere ls generally assoclaLed calclfled hllar or medlasLlnal lymph nodes.

CccupaLlonal Lung dlsease
aLlenLs wlLh slllcosls and coal mlner's pneumoconlosls ofLen develop small (<3 mm)
dlffuse lung parenchymal calclfled nodules, ofLen assoclaLed wlLh egg-shell
calclflcaLlon of hllar or medlasLlnal lymph nodes.

MlcrollLhlasls alveolarum aka ulmonary alveolar mlcrollLhlasls ls a rare ldlopaLhlc
lung dlsorder characLerlzed by Lhe lnLra-alveolar accumulaLlon of mlcrollLhs of
calclum phosphaLe. MosL are an lncldenLal flndlng on convenLlonal chesL
radlographs and seen as lnnumerable Llny calclflc denslLles.


60) on Sputum
My dear ?ln Llng,
now Lell me whaL has wasabe goL Lo do wlLh 8esplraLory medlclne!?
Why does spuLum Lurn Creen and whaL does Lhls lndlcaLe!?
WhaL ls Lhe cause of Lhe green colour of pus or nasal mucus?

Creen pus, or green nasal mucus, ls caused by lron-conLalnlng myelo-peroxldases
and oLher oxldases and peroxldases used by polymorphonuclear (Mn) granulocyLes
(neuLrophlls).

1hese shorL-llved phagocyLlslng leucocyLes avldly lngesL all sorLs of bacLerla and
lnacLlvaLe Lhem by oxldaLlve processes, lnvolvlng Lhe lron conLalnlng enzymes. 1he
resulLlng breakdown producL, comprlslng dead Mns, dlgesLed bacLerla and used
enzymes, pus, conLalns slgnlflcanL amounLs of lron, whlch glves lL lLs greenlsh colour.

AL Lhe sLarL of a u81l
nasal mucus produced aL Lhe beglnnlng ls clear and ls produced ln response Lo
Llssue damage caused by Lhe lnvadlng rhlnovlrus. lL only Lurns green a few days lnLo
Lhe lnfecLlon as neuLrophlls respond Lo clear away Lhe cellular debrls and secondary
bacLerlal lnfecLlon seLs ln.

olymorphonuclear leucocyLes are equlpped wlLh a number of enzymes, Lhe mosL
poLenL of whlch ls peroxldase.

1hls same peroxldase ls also found ln horseradlsh, glvlng lL a dlsLlncLlve green color
and a sharp blLe, as anyone who has Lrled !apanese wasabl pasLe can conflrm.

When spuLum Lurns green, spuLum has sLagnaLed lnslde Lhe resplraLory sysLem long
enough for Lhe myeloperoxldase Lo acL. lL also lmplles bacLerlal superlnfecLlon.

Wasabe anyone!?

61) on Iron stud|es
uear ?ln Llng,
My sLudenLs are frequenLly confused by lron sLudles when l ask Lhem Lo lnLerpreLe lL
as parL of Lhe work up for anaemla.
Serum Iron
lron conLalned ln blood serum ls normally bound Lo Lhe proLeln Lransferrln. lL cannoL
be floaLlng around by lLself! lron ls Loxlc!
Lach molecule of Lransferrln can LransporL Lwo molecules of lron Lo areas of Lhe
body LhaL need Lhls elemenL. 1hlnk of lL as a small lorry, Lhe pasar malam Lype.
MosL of Lhe body's lron (abouL 60) ls conLalned ln hemoglobln. AnoLher 30 ls
sLored ln ferrlLln, and a few percenL ln myoglobln. When body lron sLores lncrease
above Lhese relaLlvely normal raLlos, proporLlonally greaLer amounLs of lron are
sLored ln ferrlLln or a complex called hemoslderln.
Cenerally men have hlgher levels of serum lron Lhan women. When laboraLorles LesL
for Se lron, Lhey are LesLlng lron conLalned ln plasma LhaL ls generally bound Lo
Lransferrln.
ln mosL people, CnL? abouL 23 - 33 of Lhe Lransferrln conLalned ln Lhe serum ls
used Lo blnd lron for LransporL. SC 1PL8L A8L SA8L LC88lLS. When laboraLorles
measure serum lron Lhey also measure Lransferrln and calculaLe Lhe percenLage of
Lransferrln molecules LhaL are used Lo blnd lron.
1ota| Iron 8|nd|ng Capac|ty (1I8C) and 1ransferr|n Saturat|on (1S)
1oLal lron blndlng capaclLy: 1hls measuremenL lndlcaLes Lhe 1C1AL poLenLlal
capaclLy of Lransferrln molecules Lo blnd wlLh serum lron, lLs Lelllng you how much
load your enLlre fleeL of lorrles can carry.
When 1l8C ls aL or below Lhe low end of a laboraLory range, lL ls an lndlcaLlon LhaL
Lhere ls llmlLed capaclLy for Lransferrln molecules Lo accepL addlLlonal lron. lf LhaL
occurs ln comblnaLlon wlLh a relaLlvely hlgh measure of serum lron, lL ls llkely LhaL
Lhe ablllLy of Lransferrln Lo safely blnd serum lron ls lmpalred. ?our Loxlc producLs
are golng Lo splll on Lhe road!
lron ln Lhe plasma LhaL ls noL bound Lo Lransferrln ls called non-Lransferrln bound
lron (n18l). 1hls ls a poLenLlally Loxlc form of lron LhaL can damage body sysLems.
Cenerally, when 40 or less of Lransferrln molecules are used, lron ls consldered
safely bound. Much above LhaL, Lransferrln becomes saLuraLed and lL blndlng
capaclLy drops Lo a polnL where lL wlll no longer can efflclenLly harbor n18l. Some of
Lhe lron wlll Lhen blnd Lo oLher molecules LhaL does noL have Lransferrln's ablllLy Lo
proLecL you. 1hls causes oxldaLlve sLress, a process LhaL lf noL counLered by Lhe
body's anLloxldanL defenses, wlll over Llme resulL ln cell, Llssue and unA damage.
1ransferrln saLuraLlon percenLage (1S ) ls calculaLed by dlvldlng serum lron by 1l8C,
Lhen mulLlplylng by 100. 1he resulLlng number ls referred Lo as Lransferrln saLuraLlon
percenLage (1S ). ln people wlLh undlagnosed hemochromaLosls, Lhls number ls
ofLen above 30, and someLlmes even as hlgh as 100. 1he normal range of 1S ls
generally beLween 23-33. When Lhe percenLage ls calculaLed Lo be less Lhan 17
or hlgher Lhan 43, a condlLlon of elLher lron deflclency or lron overload ls posslble.
LlLher Loo llLLle goods or Loo much goods for your lorrles! ln elLher case, furLher
lnvesLlgaLlon ls warranLed lncludlng ferrlLln LesLlng. very low or very hlgh ferrlLln ln
comblnaLlon wlLh low or hlgh 1S can help a physlclan conflrm a dlagnosls of elLher
lron deflclency or lron overload.
Serum Ierr|t|n (SI)
lerrlLln ls a proLeln LhaL ls malnly uLlllzed Lo sLore lron for fuLure use. 1he body
requlres lron Lo make hemoglobln for blood and myoglobln for muscles. lron ln
excess of dally needs ls sLored ln ferrlLln molecules, huge sLorehouses whlch hold up
Lo 4,300 lron aLoms each!
normally, dleLary lnLake offseLs dally loss lron loss (only abouL 1 Lo 1.3 mllllgrams
per day). 1herefore, CnL? A MlnlSCu8L one gram of sLorage lron (1,000 mllllgrams)
ls adequaLe Lo meeL all foreseeable needs. 1he body rouLlnely loose lron as a resulL
of Lrauma, blood loss or Lhrough mensLruaLlon.

Powever, more Lhan one gram of sLorage lron can sLress Lhe body's ablllLy Lo
provlde a safe harbor for Lhls poLenLlally Loxlc meLal. WlLh a few excepLlons,
lncludlng evenLs of lnflammaLlon (ferrlLln 8lSLS ln lnlLAMMA1lCn eg Lhlnk of
uengue crlsls) or anemla of chronlc dlsease, a blood LesL measurlng Sl can provlde
an accuraLe surrogaLe measure of lron sLored ln Lhe body.
Cnly a very small fracLlon of Lhe body's sLored lron ls acLually sLored ln Lransferrln or
ferrlLln molecules clrculaLlng ln Lhe bloodsLream. Powever, ln healLhy lndlvlduals,
Lhe relaLlve amounL of ferrlLln found ln serum ls an accuraLe surrogaLe measure for
lron sLored ln body organs.
lerrlLln can be elevaLed even when boLh serum lron and Lransferrln saLuraLlon
percenLages are aL low-normal levels or below.
Plgh ferrlLln under Lhese clrcumsLances mlghL noL slgnal lron overload, buL can
resulL from a defense mechanlsm, an acuLe phase reacLlon. 1hls ls seen ln anemla of
chronlc dlsease, or lnflammaLory anemla.

62) on kena| funct|on
uear yln llng,
elevaLlons ln levels of blood urea and/or serum creaLlnlne do noL necessarlly
lndlcaLe sLrucLural renal dlsease.

Conversely, blood urea or serum creaLlnlne values, whlch appear Lo be wlLhln
normal, do noL by Lhemselves rule ouL slgnlflcanL reducLlon ln glomerular fllLraLlon
raLe.

Any lnLerpreLaLlon of Lhe blood levels of Lhese Lwo subsLances musL be done wlLh
Lhe awareness LhaL a varleLy of exLrarenal facLors can affecL Lhem.

WhaL ls lL whlch affecLs Lhese 2 common blochem parameLers ?
urea ls Lhe flnal producL of proLeln caLabollsm. 1he ammonla formed ln Lhls process
ls synLheslzed Lo urea ln Lhe llver. 1hls ls Lhe mosL lmporLanL caLabollc paLhway for
ellmlnaLlng excess nlLrogen ln Lhe human body. lncreased blood urea may be due Lo
prerenal causes eg cardlac fallure, dehydraLlon, lncreased proLeln caLabollsm, and
hlgh proLeln dleL, renal causes and posLrenal causes eg obsLrucLlon of Lhe urlnary
LracL from sLones, enlarged prosLaLe gland, Lumours.
1he raLe of urea producLlon ls noL consLanL. 1hls ls lLs ma[or dlsadvanLage when
used Lo monlLor renal funcLlon. lL ls elevaLed ln Lhose who consume a dleL falrly hlgh
ln proLeln and ln condlLlons characLerlzed by enhanced Llssue breakdown (eg,
hemorrhage, Lrauma, glucocorLlcold Lherapy, chemoLherapy). CerLaln anLlbloLlcs,
such as LeLracycllnes, may lnLerfere wlLh proLeln synLhesls and Lend Lo be caLabollc,
Lhereby also lncreaslng 8u levels.

Cn Lhe oLher hand, a low-proLeln dleL or llver dlsease can decrease Lhe 8u level
wlLhouL affecLlng Cl8 or renal funcLlon. My consulLanL used Lo ask me abouL llver
dlsease and 8u levels. Llver dlsease may be assoclaLed wlLh near-normal values of
boLh 8u (due Lo decreased urea producLlon) and serum creaLlnlne (due Lo muscle
wasLlng), desplLe a slgnlflcanL decllne ln renal funcLlon manlfesLed by decreased
Cl8.

ApproxlmaLely 40-30 of Lhe fllLered urea undergoes passlve reabsorpLlon ln Lhe
proxlmal Lubule. ln sLaLes of dehydraLlon and lnLravascular volume depleLlon,
proxlmal sodlum and waLer reabsorpLlon lncreases, coupled wlLh a parallel lncrease
ln Lhe reabsorpLlon of urea. 1hls resulLs ln a dlsproporLlonaLe rlse ln 8un levels
relaLlve Lo any change ln serum creaLlnlne levels. 1hls ls Lhe beauLy of undersLandlng
physlology and applylng lL Lo cllnlcal medlclne.
1he blood urea LesL ls a measure of Lhe amounL of nlLrogen ln Lhe blood LhaL comes
from urea. 1haL's why lLs also called bld urea nlLrogen.

1he mosL common cause of an elevaLed 8u, azoLemla, ls poor kldney funcLlon,
alLhough a serum creaLlnlne level ls a more speclflc measure of renal funcLlon.
LlevaLed 8u ln Lhe seLLlng of a relaLlvely normal creaLlnlne may reflecL a
physlologlcal response Lo a relaLlve decrease of blood flow Lo Lhe kldney (as seen ln
hearL fallure or dehydraLlon) wlLhouL lndlcaLlng any ln[ury Lo Lhe kldney.

Powever, an lsolaLed elevaLlon of 8u may also reflecL excesslve formaLlon of urea
wlLhouL any compromlse Lo Lhe kldneys. lncreased producLlon of urea ls seen ln
cases of moderaLe or heavy bleedlng ln Lhe upper gasLrolnLesLlnal LracL. 1hls ls
someLhlng l repeaLedly Lell my sLudenLs. 1he nlLrogenous compounds from Lhe
blood are reabsorbed as Lhey pass Lhrough Lhe Cl LracL and Lhen broken down Lo
urea by Lhe llver. Lnhanced meLabollsm of proLelns wlll also lncrease urea
producLlon, as may be seen wlLh hlgh proLeln dleLs afLer aunLle and l force feed you,
sLerold use, burns, or fever.

My consulLanL ur Mrs kula used Lo ask us abL causes of low 8u!
1hls lnclude llver problems, malnuLrlLlon (lnsufflclenL dleLary proLeln), or excesslve
alcohol consumpLlon. CverhydraLlon from lnLravenous flulds can resulL ln a low 8u
Loo. hyslologlcal changes ln renal blood flow ln pregnancy wlll also lower 8u.

?ou may be surprlsed Lo know LhaL urea lLself ls noL Loxlc. 8u ls a marker for oLher
nlLrogenous wasLe. 1hus, when renal fallure leads Lo a bulldup of urea and oLher
nlLrogenous wasLes, whaL we label as uremla ls a surrogaLe marker!

rolonged perlods of severe uremla may resulL ln Lhe skln Laklng on a grey
dlscolouraLlon or even "uremlc frosL" on Lhe skln.8ecause mulLlple varlables can
lnLerfere wlLh Lhe lnLerpreLaLlon of a 8u value, Cl8 and creaLlnlne clearance are
more accuraLe markers of kldney funcLlon. Age, sex, and welghL wlll alLer Lhe
"normal" range for each lndlvldual, lncludlng race. ln renal fallure or chronlc kldney
dlsease, 8u wlll only be elevaLed ouLslde "normal" when more Lhan 60 of kldney
cells are no longer funcLlonlng. 1hls ls a wee blL 1CC LA1L! Pence, more accuraLe
measures of renal funcLlon are generally preferred Lo assess Lhe clearance for
purposes of medlcaLlon doslng. 1he eCl8 avallable Lo us nowadays makes llfe easler
buL pls remember LhaL Lhls ls an esLlmaLe.


Dr Mrs ku|a who more than anyone e|se taught me what |t means to be a
Compass|onate hys|c|an.

63) on IV f|u|ds
uear ?ln Llng,
1hese com|ng quest|ons are Cruc|a| for a|| nouseoff|cers.

why ls lL LhaL we lnfuse uexLrose 3 and noL glve Clucose 3?
WhaL ls Lhe dlfference lf any?
"Clucose represenLs Lhe Lwo forms sugars, lsomers, LhaL mlrror each oLher, d-
glucose and l-glucose. Cnly d-glucose ls blologlcally acLlve and ls chemlcally known
as dexLrose monohydraLe."
uear ?ln Llng,
WhaL ls ParLman's and when do you use lL?

ParLmann's soluLlon ls a super yummy poLpourrl needed for elecLrolyLe losses
* lL conLalns poLasslum and calclum ln concenLraLlons LhaL approxlmaLe Lhe free
(lonlzed) concenLraLlons ln plasma.

* 1he addlLlon of Lhese caLlons requlres a reducLlon ln sodlum concenLraLlon for
elecLrlcal neuLrallLy, so ParLmann's has a lower sodlum concenLraLlon Lhan elLher
lsoLonlc sallne or plasma.
* 1he addlLlon of lacLaLe (28 mLq/l) slmllarly requlres a reducLlon ln chlorlde
concenLraLlon.

LacLaLed 8lnger soluLlon has an elecLrolyLe composlLlon whlch mlmlcs Lhe lonlc
concenLraLlons of calclum, poLasslum, and chlorlde ln plasma more closely Lhan
lsoLonlc sallne. 1hls ls Lhe AdvanLage.

Why LacLaLe?

1he added lacLaLe ls converLed Lo blcarbonaLe by Lhe llver. 1he lnLenLlon was for Lhe
blcarbonaLe Lo acL as a buffer ln paLlenLs wlLh meLabollc acldosls, however, Lhls
effecL ls noL a cllnlcally slgnlflcanL one. ls remember LhaL Lhe added calclum may
acL as a blnder for many drugs and lmpalr boLh bloavallablllLy and efflcacy.
ln conLrasL, normal (lsoLonlc) sallne 0.9 n/S
* lL ls a soluLlon of 0.9 sodlum chlorlde ln waLer, lL conLalns LCuAL quanLlLles of
sodlum and chlorlde (134 mLq/l). 1he plasma ls nC1 llke LhaL, our Cl ls much2 lower!
* lL has a much hlgher concenLraLlon of chlorlde compared Lo plasma and lnfuslon of
large volumes of lsoLonlc sallne can produce a meLabollc acldosls.

So be careful when you Lell me LhaL n/S ls glven a loL. now do you see clearer why
you need Lo glve some "free waLer" Loo!

ulsorders of sodlum concenLraLlon are nearly always caused by excess free waLer
(hyponaLraemla) or free waLer loss (hypernaLraemla).
crysLallolds wlll dlsLrlbuLe beLween Lhe lnLravascular space and Lhe lnLersLlLlal space.
- Pence, paLlenLs undergolng large volume fluld resusclLaLlon are aL hlgh rlsk for
developlng pulmonary and generallzed lnLersLlLlal edema, parLlcularly wlLh a
preexlsLlng sLaLe of fluld over- load (e.g., congesLlve hearL fallure and renal fallure).
now you see why we cannoL [usL glve more!
We dlscussed "free waLer", whlle lv dexLrose soluLlons are beneflclal ln Lhe
managemenL of glucose-deflclenL sLaLes, eg fasLlng pre and posL operaLlons, lL ls Lhe
leasL poLenL volume expander of Lhe crysLallold soluLlons for once Lhe dexLrose ls
rapldly Laken up, lree WaLer ls now avallable whlch wlll dlffuse lnLo cells. lor
rehydraLlon lL ls useful.

uexLrose 3 ls hence a 'MalnLenance lluld'. lLs noL good for fluld expanslon buL ls
good Lo supply waLer. lf your paLlenL ls loslng waLer because of fever, Lachypnoea,
eLc, waLer needs Lo be supplled!

uexLrose 3 conLalns 3g of dexLrose (u-glucose) per 100ml of waLer. 1hls glucose ls
rapldly meLabollzed and Lhe remalnlng free waLer dlsLrlbuLes rapldly and evenly
LhroughouL Lhe body's fluld comparLmenLs. So shorLly afLer lv admlnlsLraLlon of
1000ml 3 dexLrose, 670ml waLer wlll be added Lo lCl and 330ml waLer Lo LCl.
uexLrose 3 ls an lsoLonlc soluLlon.

1he neL effecL ls of admlnlsLerlng pure waLer, so lL ls dlsLrlbuLed LhroughouL Lhe LoLal
body waLer.
8e cauLlous Lhough LhaL we [usL cannoL keep on glvlng crysLallolds. Cne of Lhe
sLrongesL argumenLs agalnsL Lhe use of crysLallold flulds has been LhaL Lhey cause a
dlluLlonal hypoalbumlnemla LhaL puLs paLlenLs aL lncreased rlsk for developlng
pulmonary edema. WaLch ouL for Lhose basal crepLs as l repeaLedly Lold you all
klddles!!!
now you all know why l geL very upseL when my sLudenLs do noL ausculLaLe Lhe
lungs because lLs "an abdomlnal problem ma!"

'Mah your head' l would scream!!
8ecause Lhe osmolarlLy of normal sallne maLches LhaL of Lhe serum, lL ls an excellenL
fluld for volume replacemenL. Pence ln hypovCLALMlC sLaLes, Lhls ls Lhe fluld of
cholce.

- PypoLonlc flulds such as u3W should never be used Lo replace volume. 1hey are
Lhe waLer Lrucks ln Lhls dry and hoL season.
- LacLaLed 8lnger's soluLlon ls commonly used for surglcal or Lrauma paLlenLs
because of elecLrolyLe losses, however, only nS can be glven ln Lhe same llne wlLh
blood componenLs. Calclum ln lv flulds means an excluslve llne noL Lo mlx wlLh oLher
Lhlngs!
now uexLrose 3 ln n/S aka uexLrose sallne ls noL as popular now as before. ?ln
Llng ls unfamlllar wlLh lL. 1lmes have changed. lL was commonly used when l was a
young docLor. lL sLlll has a role desplLe belng a hyperLonlc fluld and can be used as
malnLenance fluld for suspecLed menlnglLls, acuLe neurologlcal condlLlons where
you do nC1 wanL Lhe hypoLonlc free waLer of u3 once Lhe dexLrose ls Laken up Lo
preclplLaLe cerebral odema,
and ln gasLroenLerlLls wlLh sodlum losses or when Lhe serum sodlum ls low.
1he ually malnLenance fluld requlremenLs vary beLween lndlvlduals based on welghL
and sex.
Lg ln a 70 kg male = 2.3 - 3.0L waLer ls needed, and only 120 - 140 mmol sodlum Lo
replace loss ln sweaL and urlne. Cur bodles are super efflclenL salL conservlng
machlnes. Cne llLre or 2 "plnLs ln local colloqulal" of n/S wlll provlde 134mmols of
sodlum, more Lhan enough for basal needs of replacemenL!

Pence, a reglme for eg of 2L 3 uexLrose + 1L normal sallne wlll provlde 3L waLer
and 134 mmol sodlum.
1hls ls whaL ?ln Llng Lells me she prescrlbes ofLen for malnLenance lv reglmes ln
fasLlng paLlenLs.

8uL how much calorles dld she glve?

know LhaL 3 dexLrose means Lhe soluLlon conLalns 3g/100ml of soluLlon. Pence 1
llLre has 30 grams whlch LranslaLes Lo 30 x 4 calorles whlch ls 200 calorles. 2 l of u3
a day wlll CnL? provlde 400 calorles. WhaL does Lhls mean? l haLe all Lhese numbers
as lL ls llke saylng "puL 30 grams of salL ln Lhe soup" ln cookbooks!

A bowl of rlce ls 200 calorles! 1hls ls equal Lo 2 bowls of LAln rlce per day. no
wonder your paLlenL ls loslng welghL! A plaLe of nasl lemak wlLh chlcken Lhrown ln ls
300 calorles, hence we are noL dolng a good [ob wlLh our paLlenLs nuLrlLlon.

now flnally oLasslum. 1hls ls essenLlal Loo. We need 0.3 Lo 1 mmol per kg 8W le abL
33 Lo 70 mmol per day.

1 Cm of kCl ls equal Lo 13.3 mmol of oLasslum.
so lf we glve 1 gm ln each lnfuslon ln alLernaLe "plnLs" we wlll glve 3 gms le 13.3 x 3 =
40mmols per day. !usL enough!

now all Lhe above ls for a "nC8MAL" person wlLh no addlLlonal losses.

ually fluld requlremenLs lncrease ln lllness:
lever (300 ml/day for every degree above 37oC)
8reaLhlessness and Lachypnoea
ularrhoea and vomlLlng
Paemorrhage
Surglcal dralns, sLoma and flsLulae
olyurla
1hlrd space losses (pancreaLlLls, bowel obsLrucLlon, and afLer laparoLomy)
Sl8S - caplllary leak

LlecLrolyLe losses musL be facLored ln as well.
A 8uSL ls lndlspensable as an ald.

As a sLarry eyed Pouseofflcer.

64) on 8ony Secondar|es
uear ?ln Llng,

we ofLen see secondarles ln bones and commonly Lhey are osLeolyLlc leslons.
Cccaslonally we see Pyperdense secondarles! WhaL are your LhoughLs when you see
one? Where do Lhey arlse from?

ScleroLlc (or blasLlc) bony meLasLases can arlse from a number of dlfferenL prlmary
mallgnancles, lncludlng:

prosLaLe carclnoma : mosL common
breasL carclnoma (may be mlxed)
LranslLlonal cell carclnoma (1CC)
carclnold
medulloblasLoma
neuroblasLoma
muclnous adenocarclnoma of Lhe gasLrolnLesLlnal LracL: , e.g. colon carclnoma
lymphoma

ln general, Lhe splne ls Lhe mosL common locaLlon of meLasLaLlc dlsease. MeLasLases
dlsLal Lo Lhe knee and elbow are exLremely uncommon, buL approxlmaLely 30 of
Lhese acral meLasLases are secondary Lo prlmary lung Lumors. Carclnomas, such as
Lhose of Lhe breasL and prosLaLe, rarely exhlblL such a dlsLlncL paLLern.

CompuLed Lomography scannlng: MosL senslLlve lmaglng modallLy Lo deLecL bone
desLrucLlon, provldlng Lhe besL assessmenL of Lhe exLenL of corLlcal desLrucLlon
8one scannlng: very senslLlve sLudy for Lhe deLecLlon of occulL leslons and Lhe
assessmenL of Lhe blologlc acLlvlLy of leslons


rof Lsha uasgupLa: l can'L reslsL Lo pen down my mnemonlc for Lumours whlch
cause bone meLasLasls. lL ls u8Llk 1(olleL) ( u8LlC 1ClLL1) for prosLaLe,u for
uLerus, 8 for breasL and bladder,L for lungs,l for lnLesLlne aka colon,k for kldneys
and 1 for Lhyrold.


6S) on Sept|caem|a
uear ?ln Llng,

WhaL ls Csler's Lrlad?

lL ls also known as Lhe AusLrlan Lrlad
lL descrlbes Lhe 1rlad of pneumonla, endocardlLls, and menlnglLls occurrlng
slmulLaneously or subsequenLly ln a paLlenL.
1he Lrlad was lnlLlally reporLed by Lhe AusLrlan paLhologlsL 8lchard Ladlslaus Peschl
(1824-1881) ln 1862, and laLer by Csler ln 1881.

1hls ls acLually a rare comblnaLlon of SLrepLococcal sepLlcaemla, wlLh SLrepLococcus
pneumonlae endocardlLls and wlLh SLrep pneumonla, and SLrep menlnglLls. CfLen
assoclaLed wlLh alcohol abuse, morLallLy ls exLremely hlgh.

SLrepLococcus pneumonlae ls responslble for a remarkable array of dlsease
processes. Lxamples of Lhese lnfecLlons lncludes pancreaLlc and llver abscesses,
aorLlLls, glnglval leslons, LesLlcular and Lubo-ovarlan abscesses, and necroLlzlng
fascllLls. CurrenLly, mulLldrug-reslsLanL S. pneumonlae remalns suscepLlble Lo
vancomycln and several new Lhlrd-generaLlon fluoroqulnolones.

l recall ln fear when l remember how we nonchalanLly handled agar plaLes Leemlng
wlLh SLrep pneumonla as second year sLudenLs dolng Mlcroblology pracLlcals!


66) on Iron supp|ement
uear ?ln Llng,

Should a person wlLh Lhalassemla LralL avold lron, such as lron-forLlfled vlLamlns?

lron LableLs or lron-supplemenLed vlLamlns should be Laken only as dlrecLed by a
physlclan Lo LreaL 8CvLn AC1uAL lron deflclency or Lo prevenL lron deflclency ln
hlgh rlsk clrcumsLances (e.g pregnancy).

eople wlLh Lhalassemla LralL (Lhalassemla mlnor) are noL per se aL greaLer rlsk of
compllcaLlons from lron ln Lhe dleL Lhan anyone else ln Lhe general populaLlon. So
eaL your green veggles, llver and sLeak. no lssue Lhere.

My concern as greaLly emphazlsed ln class ls mlsdlagnoslng Lhalassaemla mlnor as
lron deflclency, or ln paLlenLs wlLh colncldenL beLa Lhalassaemla and lron deflclency,
noL reallslng LhaL Pb elecLrophoresls done Lhen wlll nC1 demo an elevaLed PbA2
paLLern as Lhe lron deflclency wlll noL allow more PbA2 Lo be formed. Pence ln
paLlenLs wlLh lron deflclency, Lhe lron deflclL musL be correcLed before Lhe Pb
elecLrophoresls ls ordered.

Can Lhe anemla produced by Lhalassemla be correcLed or lmproved by Laklng more
lron?

ln Lhe absence of concomlLanL lron deflclency, lron supplemenLaLlon wlll nelLher
correcL nor lmprove anemla due Lo Lhalassemla.

lor people wlLh boLh lron deflclency and Lhalassemla, eg glrls wlLh heavy menses,
lron replacemenL wlll lessen Lhe severlLy of Lhe anemla, unLll Lhe lron deflclency ls
correcLed. 1he blood counL wlll level off and no furLher lmprovemenL wlll occur. We
need Lo conflrm lron deflclency and a slmple cheap screenlng LesL ls Se ferrlLln.


67) on Iaund|ce
uear ?ln Llng,
are you aware LhaL mlld uncon[ugaLed hyperblllrublnaemla may acLually be
beneflclal??
lor eg, CxldaLlve sLress ls consldered a key elemenL ln Lhe progresslon of non-
alcohollc faLLy llver Lo non-alcohollc sLeaLohepaLlLls (nASP). uncon[ugaLed blllrubln
ls Lhe maln endogenous llpld anLloxldanL and ls cyLoproLecLlve ln dlfferenL Llssues
and organs. 8lllrubln can acL as an lmporLanL cyLoproLecLor of Llssues LhaL are poorly
equlpped wlLh anLloxldanL defense sysLems, lncludlng myocardlum and nervous
Llssue.
So perhaps condlLlons LhaL cause mlld chronlc uncon[ugaLed Pyperblllrublnaemla
llke CllberL's Syndrome may have survlval beneflLs and perhaps ls a deslrable
muLaLlon and may be among genes consldered longevlLy genes. 1here are sLudles
LhaL show a correlaLlon beLween CllberL's Syndrome and lower lncldence of cerLaln
dlseases such as arLerlosclerosls and cancer.
Llpld oxldaLlon and formaLlon of oxygen radlcals are lmporLanL elemenLs of arLerlal
plaque formaLlon and aLherosclerosls, and are lnvolved ln Lhe paLhophyslology of
coronary arLery dlsease. 8ecause uncon[ugaLed blllrubln has anLloxldanL properLles,
lL has been suggesLed LhaL lL may have a proLecLlve role ln Lhe aLheroscleroLlc
process.
8oLh con[ugaLed blllrubln, and uncon[ugaLed blllrubln were all noLed Lo be effecLlve
scavengers of peroxyl radlcals and Lo be able Lo proLecL human LuL agalnsL
peroxldaLlon. under physlologlcal condlLlons, Lhe predomlnanL clrculaLory form of
blllrubln ls Lhe uncon[ugaLed, albumln-bound form.
LlpoproLelns, and parLlcularly LuL, are hlghly suscepLlble Lo oxldaLlon, and lL ls
known LhaL Lhe aLherogenlc process lnvolves upLake of oxldlzed LuL by lnLlmal
macrophages, leadlng Lo Lhe accumulaLlon of llpld-rlch foam cells. Clven Lhe
anLloxldanL capaclLy of blllrubln, lL ls plauslble LhaL blllrubln proLecLs llplds and
llpoproLelns agalnsL oxldaLlon and Lhereby offers proLecLlon agalnsL aLherogenesls.
ln 1994, SchwerLner eL al were Lhe flrsL Lo observe a slgnlflcanL lnverse correlaLlon
beLween LoLal blllrubln plasma concenLraLlons and Lhe prevalence of CAu. 1hls
lmporLanL flndlng lndlcaLed LhaL a lower Lhan normal serum blllrubln concenLraLlon
ls assoclaLed wlLh Lhe presence of lschemlc hearL dlsease!
8relmer eL al observed a u-shaped relaLlonshlp beLween clrculaLlng blllrubln
concenLraLlons and cardlovascular rlsk, leadlng Lo Lhe concluslon LhaL low
concenLraLlons of serum blllrubln are assoclaLed wlLh lncreased rlsk of lschemlc
hearL dlsease. 1hese and oLher lnvesLlgaLors found LhaL plasma blllrubln correlaLed
lnversely wlLh several known rlsk facLors for CAu, such as smoklng, LuL-cholesLerol,
dlabeLes, and obeslLy, and correlaLed dlrecLly wlLh Lhe proLecLlve facLor PuL-
cholesLerol.
Low blllrubln was suggesLed as an lndependenL rlsk facLor for CAu, and an lnverse
correlaLlon was demonsLraLed beLween blllrubln concenLraLlon and CAu morbldlLy.
lurLher supporL for Lhe exlsLence of Lhls lnverse correlaLlon came from Lhe work of
PunL eL al, who descrlbed a geneLlc varlaLlon ln blllrubln concenLraLlon, wlLh
lndlvlduals wlLh early CAu dlsplaylng lower blllrubln Lhan unaffecLed persons.


68) a typ|ca| 8eds|de c|ass
notes taken by Dr Ch|n M|ng Lee when she was a year3 student
8eds|de 1each|ng (Dr. Wong)
03/03/2011

1. Wa|ks |n

8lghL hemlpleglc
galL
SLroke (lefL slded, lnLernal capsule, posLerlor llmb).
Arm flexed, pronaLed, adducLed.
Leg abducLed, LwlsLed ln (have Lo swlng when he walks).
unllaLeral weakness and spasLlclLy wlLh Lhe upper
exLremlLy held ln flexlon and Lhe lower exLremlLy ln
exLenslon. 1he fooL ls ln exLenslon so Lhe leg ls "Loo long"
Lherefore, Lhe paLlenL wlll have Lo clrcumducL or swlng
Lhe leg around Lo sLep forward. Seen wlLh a UMN |es|on.
Cerebellar aLaxla Looks llke someone drunk walklng.
urunken galL, sLagger slde Lo slde, wlden legs for balance.
CalL ls wlde-based wlLh Lruncal lnsLablllLy and lrregular
lurchlng sLeps whlch resulLs ln laLeral veerlng and lf
severe, falllng. 1hls Lype of galL ls seen ln m|d||ne
cerebe||ar d|sease. lL can also be seen wlLh severe loss of
proprlocepLlon (sensory atax|a).
Shuffllng galL arklnson's dlsease.
Pand pronaLed.
Seen wlLh rlgldlLy and hypoklnesla from basa| gang||a
d|sease. 1he paLlenL's posLure ls sLooped forward. CalL
lnlLlaLlon ls slow and sLeps are small and shuffllng, Lurnlng
ls en bloc llke a sLaLue.
Plgh sLepplng galL 8llaLeral - Syphllls. Lose proprlocepLlon, so sLomp feeL on
floor.
unllaLeral - uamage Lo Lhe sclaLlc nerve.
MosL ofLen seen ln perlpheral nerve dlsease where Lhe
dlsLal lower exLremlLy ls mosL affecLed. 8ecause Lhe fooL
dorslflexors are weak, Lhe paLlenL has a hlgh sLepplng galL
ln an aLLempL Lo avold dragglng Lhe Loe on Lhe ground.

hLLp://llbrary.med.uLah.edu/neurologlcexam/hLml/galLabnormal.hLml12

2. S|ts down

Cower's slgn Weakness of Lhe proxlmal muscles, namely Lhose of Lhe lower
llmb. 1he slgn descrlbes a paLlenL LhaL has Lo use hls hands and
arms Lo "walk" up hls own body from a squaLLlng poslLlon due
Lo lack of hlp and Lhlgh muscle sLrengLh.
Classlcally seen ln uuchenne muscular dysLrophy, buL also
presenLs lLself ln cenLronuclear myopaLhy, myoLonlc dysLrophy
and varlous oLher condlLlons assoclaLed wlLh proxlmal muscle
weakness.


ALheLosls ConLlnuous sLream of slow, slnuous, wrlLhlng movemenLs,
Lyplcally of Lhe hands and feeL. Sald Lo be caused by damage Lo
Lhe corpus str|atum of Lhe braln - Speclflcally Lo Lhe putamen. lL
can also be caused by a leslon of Lhe moLor Lhalamus.
Corrlgan's 8apld rlse and fall of pulse of Lhe caroLld arLery on lnspecLlon
slgn whlch ls conslsLenL wlLh Lhe wlde pulse pressure of aorLlc
regurglLaLlon.
Collapslng pulse.
Larly dlasLollc murmur.
Wlde pulse pressure (need readlng wlLh hearL beaL).
uanclng uvula.
uanclng caplllarles wlLh beaL.
lasclculaLlon normal when sLlck ouL Longue.
1o flnd paLhology, leave Longue ln mouLh.
LMn - MoLor neuron dlsease - lasclculaLlon everywhere.

3. Iace and others

Lndocrlne Crave's, acromegaly, Cushlng's.
CvS SLernoLomy (CA8C), hyperllpldemla (arcus llpldus), cenLral
cyanosls, clubblng, congenlLal cyanoLlc hearL dlseases,
Llsenmenger syndrome.
neurology 8ell's palsy : Absence of forehead wrlnkles, nasolablal fold
(7Lh).
Losls, eyeball down and ouL (3rd).
nephrology C8l - Sallow face (llghLer Lhan Lea colour), uremlc breaLh.
nephroLlc syndrome - erl-orblLal edema.
PepaLology Alcohollc clrrhosls - AsclLes, gynecomasLla, female publlc halr
dlsLrlbuLlon.
8heumaLology SLL - 8uLLerfly rash.
8A + Swan neck deformlLy + ury eyes and mouLh = S[ogren's
syndrome.
uermaLomyoslLls - PelloLrope rash.

4. nands and others

Pands Acromegaly (spade llke).

uarkenlng of palmar creases (+ plgmenLaLlon ln mouLh) - AC1P,
Addlson's dlsease. unable Lo produce corLlsol, so feedback ls Lo
lncrease Lhe producLlon of AC1P (same sLrucLure as MSP),
leadlng Lo hyperplgmenLaLlon.

kaynaud's phenomenon : WhlLe ! 8lue ! lnk
- 1he sympLoms lnclude several cycllc color changes
1. When exposed Lo cold LemperaLures, Lhe blood supply Lo Lhe
flngers or Loes, and ln some cases Lhe nose or earlobes, ls
markedly reduced, Lhe skln Lurns pale or whlLe (called pallor),
and becomes cold and numb.
2. When Lhe oxygen supply ls depleLed, Lhe skln colour Lurns
blue (called cyanosls).
3. 1hese evenLs are eplsodlc, and when Lhe eplsode subsldes or
Lhe area ls warmed, Lhe blood flow reLurns and Lhe skln
colour flrsL Lurns red (rubor), and Lhen back Lo normal, ofLen
accompanled by swelllng, Llngllng, and a palnful "plns and
needles" sensaLlon.

- ln men, Lhls phenomenon someLlmes occurs ln lndlvlduals
who work wlLh vlbraLlng lnsLrumenLs.
- ln paLlenLs wlLh sysLemlc scleroderma, aLLacks are, ln
general, more frequenL and more severe.

Cervlcal spondyllLls.
Csler's nodes (palnful), !aneway leslons (palnless).
U|nar c|aw - 4Lh and 3Lh flngers drawn Lowards Lhe back of Lhe
hand aL Lhe flrsL knuckle and curled Lowards Lhe palm aL Lhe
second and Lhlrd knuckles.



Dupuytren's contracture |n CkI - llxed flexlon conLracLure of
Lhe hand where Lhe flngers bend Lowards Lhe palm and cannoL
be fully exLended (sLralghLened). uue Lo conLracLures of Lhe
palmar aponeurosls (or palmar fascla).



M|xed C1 d|sease ("Sharp's syndrome")
- AuLolmmune dlsease.
- Comblnes feaLures of scleroderma, myoslLls, SLL, and 8A
(wlLh some sources addlng polymyoslLls, dermaLomyoslLls,
and lncluslon body myoslLls), and ls Lhus consldered an
overlap syndrome.
- Commonly causes [olnL paln/swelllng, malalse, 8aynaud's
phenomenon, S[gren's syndrome, muscle lnflammaLlon,
sclerodacLyly (Lhlckenlng of Lhe skln of Lhe pads of Lhe
flngers).
- LlchenlflcaLlon - 1hlck, leaLhery skln, usually Lhe resulL of
consLanL scraLchlng and rubblng.




L|vedo ret|cu|ar|s
- MoLLled reLlculaLed vascular paLLern LhaL appears llke a lace-
llke purpllsh dlscoloraLlon of Lhe lower exLremlLles. 1he
dlscoloraLlon ls caused by swelllng of Lhe medlum velns (noL
small) ln Lhe skln, whlch makes Lhem more vlslble. So lL can
be caused by any condlLlon LhaL makes venules swell.
- 8road dlfferenLlal dlagnosls, broadly dlvlded lnLo posslble
blood dlseases, auLolmmune (rheumaLologlc) dlseases,
cardlovascular dlseases, cancers, and endocrlne dlsorders.
SLL, anLl-phosphollpld syndrome, Sneddon's syndrome.




8outonn|ere deform|ty (8uLLon Lhrough buLLon hole")
- ueformed poslLlon of Lhe flngers or Loes, ln whlch Lhe [olnL
nearesL Lhe knuckle (l) ls permanenLly benL Loward Lhe
palm whlle Lhe furLhesL [olnL (ul) ls benL back away (l
hyperflexlon wlLh ul hyperexLenslon). lL ls commonly
caused by ln[ury or by an lnflammaLory condlLlon llke 8A.
- 1hls flexlon deformlLy of Lhe proxlmal lnLerphalangeal [olnL ls
due Lo lnLerrupLlon of Lhe cenLral sllp of Lhe exLensor Lendon
such LhaL Lhe laLeral sllps separaLe and Lhe head of Lhe
proxlmal phalanx pops Lhrough Lhe gap llke a flnger Lhrough
a buLLon hole (Lhus Lhe name, from lrench bouLonnlre
"buLLon hole"). 1he dlsLal [olnL ls subsequenLly drawn lnLo
hyperexLenslon because Lhe Lwo perlpheral sllps of Lhe
exLensor Lendon are sLreLched by Lhe head of Lhe proxlmal
phalanx (noLe LhaL Lhe Lwo perlpheral sllps are lnserLed lnLo
Lhe dlsLal phalanx, whlle Lhe proxlmal sllp ls lnserLed lnLo Lhe
mlddle phalanx). 1hls deformlLy makes lL dlfflculL or
lmposslble Lo exLend Lhe proxlmal lnLerphalangeal [olnL.



Scleroderma, psorlasls, vascullLls.

1ophaceous gout - A chronlc form of gouL. nodular masses of
urlc acld crysLals (Lophl) are deposlLed ln dlfferenL sofL Llssue
areas of Lhe body. Lven Lhough Lophl are mosL commonly found
as hard nodules around Lhe flngers, aL Lhe Llps of Lhe elbows,
and around Lhe blg Loe, Lophl nodules can appear anywhere ln
Lhe body (e.g. ears, vocal chords, splnal cord).

D|g|ta| gangrene
- ALherosclerosls.
- vascullLls.
- lgA nephropaLhy (8erger's) - rlmary lgA nephropaLhy ls
characLerlzed by deposlLlon of Lhe lgA anLlbody ln Lhe
glomerulus. 1here are oLher dlseases assoclaLed wlLh
glomerular lgA deposlLs, Lhe mosL common belng Penoch-
Schnleln purpura (PS), whlch ls consldered by many Lo be
a sysLemlc form of lgA nephropaLhy. PS presenLs wlLh a
characLerlsLlc purpurlc skln rash, arLhrlLls, and abdomlnal
paln and occurs more commonly ln young adulLs.

Marfan's
- ArachnodacLyly (flngers are abnormally long and slender ln
comparlson Lo Lhe palm of Lhe hand).
- PyperexLenslblllLy.
1ox|c shock syndrome (1SS)
- oLenLlally faLal lllness caused by a bacLerlal Loxln.
- SLaphylococcus aureus and SLrepLococcus pyogenes.
- ulffuse rash, lnLense eryLhroderma, blanchlng wlLh
subsequenL desquamaLlon, especlally of Lhe palms and soles.
- 1ampons and sepLlcemla.



1y|os|s - 8are lnherlLed dlsease characLerlzed by excess skln on
Lhe palms and soles. AffecLed paLlenLs have a much hlgher
probablllLy of developlng esophageal cancer Lhan Lhe general
populaLlon.

nall-plLLlng - sorlasls.
8eau's llnes - unwell.
kollonychla - lron deflclency.
lgmenLaLlon of nalls - Zldovudlne. 8lulsh or brownlsh-black
dlscoloraLlon of nalls may develop durlng Lhe flrsL monLh or Lwo
of zldovudlne Lherapy and usually dlsappears wlLhln 2 monLhs lf
Lhe drug ls dlsconLlnued. ulscoloraLlon may occur as longlLudlnal
sLreaks or Lransverse bands.

Charcot Mar|e 1ooth
- An lnherlLed dlsorder of nerves (neuropaLhy) LhaL Lakes
dlfferenL forms.
- CharacLerlzed by loss of muscle Llssue and Louch sensaLlon,
predomlnanLly ln Lhe feeL and legs buL also ln Lhe hands and
arms ln Lhe advanced sLages of dlsease.
- usually, Lhe lnlLlal sympLom ls fooL drop early ln Lhe course
of Lhe dlsease. 1hls can also cause claw Loe, where Lhe Loes
are always curled. WasLlng of muscle Llssue of Lhe lower
parLs of Lhe legs may glve rlse Lo "stork |eg" or "|nverted
bott|e" appearance. Weakness ln Lhe hands and forearms
occurs ln many people laLer ln llfe as Lhe dlsease progresses.
- 8reaLhlng can be affecLed ln some, so can hearlng, vlslon,
and Lhe neck and shoulder muscles. Scollosls ls common. Plp
sockeLs can be malformed. CasLrolnLesLlnal problems can be
parL of CM1, as can chewlng, swallowlng, and speaklng (vocal
cords aLrophy). A Lremor can develop as muscles wasLe.
Clubblng

LndocardlLls.
CongenlLal cyanoLlc hearL dlsease.
uA compllcaLed by Llsenmenger (only Loes, dlsLal Lo SCA).
8ronchlecLasls.
Lung abscess.
CA lung.
ldlopaLhlc lung dlsease.
l8u.
Llver dlsease.
1hyroLoxlcosls.
ALrlal myxoma
llbrous alveollLls.
* nC1 ln CCu.
1henar
muscles
llaLLened - Medlan nerve palsy.
8llaLeral carpal Lunnel
Acromealgy
lnreased welghL.
Menopausal
uysLrophla
myoLonlca

Chronlc, slowly progresslng, hlghly varlable lnherlLed mulLl-sysLemlc
dlsease.
SLlff handshake, cannoL leL go.
Sad, shabby, droopy face.
WasLlng of Lhe face (Lrlangular face, lower half of face sunken).
Marked wasLlng of Lhe neck muscles - May have floppy neck.
8llaLeral pLosls.



8heumaLold
arLhrlLls


Swan neck deformlLy - ul hyperflexlon wlLh l
hyperexLenslon.
8ouLonnlere's deformlLy
Z deformlLy of Lhumb - PyperexLenslon of Lhe lnLerphalangeal
[olnL, and flxed flexlon and subluxaLlon of Lhe
meLacarpophalangeal [olnL.
llnger ulnar devlaLlon (MC).
PepaLology
and nalls
almar eryLhema - Llver fallure, 8v, pregnancy, LhyroLoxlcosls.
1erry's nall (leukonychla, whlLe nalls) - Pypoalbumlnaemla
caused by nephroLlc syndrome.
Palf and half nalls ("Llndsay's nalls")
- roxlmal porLlon of Lhe nall whlLe and Lhe dlsLal half red,
plnk, or brown, wlLh a sharp llne of demarcaLlon beLween Lhe
Lwo halves.
- Chronlc renal fallure.
Lhlers-uanlos syndrome (LuS)
- A group of more Lhan 10 dlfferenL lnherlLed dlsorders, all
lnvolve a geneLlc defecL ln collagen and connecLlve-Llssue
synLhesls and sLrucLure.
- Can affecL Lhe skln, [olnLs, and blood vessels.

Scar|et fever
Caused by exoLoxln released by SLrepLococcus pyogenes.
CharacLerlzed by
(1) Sore LhroaL.
(2) lever.
(3) 8rlghL red Longue wlLh a sLrawberry" appearance - lnflamed red paplllae.
Seen ln kawasakl dlsease, Loxlc shock syndrome, and scarleL fever. May mlmlc
glosslLls or 812 vlLamln deflclency.
* kawasak| d|sease - An auLolmmune dlsease LhaL manlfesLs as a sysLemlc
necroLlzlng medlum-slzed vessel vascullLls and ls largely seen ln chlldren less Lhan
3 years of age. lL affecLs many organ sysLems, malnly Lhose lncludlng Lhe blood
vessels, skln, mucous membranes and lymph nodes, however, lLs mosL serlous
effecL ls on Lhe hearL where lL can cause severe coronary arLery aneurysms ln
unLreaLed chlldren.













(4) CharacLerlsLlc rash.
- llne, red, and rough-LexLured. 8lanches upon pressure.
- Cenerally sLarLs on Lhe chesL, armplLs, and behlnd Lhe ears.
- Spares Lhe face (alLhough some clrcumoral pallor ls characLerlsLlc).
- Worse ln Lhe skln folds. 1hese asLla llnes (where Lhe rash runs LogeLher ln
Lhe armplLs and groln) appear and can perslsL afLer Lhe rash ls gone.
- May spread Lo cover Lhe uvula.

8eddened sore LhroaL, a fever aL or above 101 l (38.3 C), and swollen glands ln Lhe
neck. 1he Lonslls and back of Lhe LhroaL may be covered wlLh a whlLlsh coaLlng, or
appear red, swollen, and doLLed wlLh whlLlsh or yellowlsh specks of pus. Larly ln Lhe
lnfecLlon, Lhe Longue may have a whlLlsh or yellowlsh coaLlng. Also, an lnfecLed
person may have chllls, body aches, nausea, vomlLlng, and loss of appeLlLe.




nansen's d|sease]Leprosy
Chronlc dlsease caused by Lhe bacLerla MycobacLerlum leprae and
MycobacLerlum lepromaLosls.
rlmarlly a granulomaLous dlsease of Lhe perlpheral nerves and mucosa of Lhe
upper resplraLory LracL, skln leslons are Lhe prlmary exLernal slgn.
LefL unLreaLed, leprosy can be progresslve, causlng permanenL damage Lo Lhe
skln, nerves, llmbs and eyes. ConLrary Lo folklore, leprosy does noL cause body
parLs Lo fall off, alLhough Lhey can become numb or dlseased as a resulL of
lnfecLlon, lnfecLlon resulLs ln Llssue loss, so flngers and Loes become shorLened
and deformed as Lhe carLllage ls absorbed lnLo Lhe body.


69) Cn DCLS!
uear ?ln Llng,
We musL noL allow uopeys ln medlclne! 1haL ls only allowed ln Lhe 7 dwarfs!
no apex beaL felL - WP??
8emember uCLS

uexLrocardla (pls don'L say Lhls flrsL!),
CbeslLy,
leural/erlcardlal effuslon,
Lmphysema, Lmpyema
Shock, Sllly medlcal sLudenL


70) on Lat|ng
?ln llng says l feed her Loo much aL dlnner and hence she ls sleepy posL dlnner! 1rue
or false?
ls Lhere a physlologlcal basls?
uld your Leachers ln year 1 Leach you well?


Plgh-carb, hlgh-faL foods (llke mosL Mslan meals esp my beloved Pokklen mee)
Lrlgger a neural response when lL reaches Lhe small lnLesLlne. 1haLs why your
sleeplness ls noL lnsLanL buL afLer an hour or so.
1haL response, vla Lhe parasympaLheLlc nervous sysLem, focus on movlng Lhe
lnLesLlnes and dlgesLlng Lhe food raLher Lhan sLudy. 1hlnk of Lhe pyLhon afLer
swallowlng a chlcken... lL lles flaL and unmovlng llke my med sLudenLs!

A group of braln cells called orexln neurons are found ln Lhe hypoLhalmus and are
very senslLlve Lo glucose levels, whlch splke afLer a CPC meal. 1hese neurons
produce orexln, whlch moderaLes wakefulness ln Lhe braln.

8uL orexln lsn'L Lhe only sleep-relaLed neurohormone affecLed by food. As Lhe
quanLlLy of food lncreases, so Loo ls Lhe amounL of lnsulln released. 1he lnsulln
lncreases Lhe amounL of seraLonln and melaLonln LhaL flood Lhe braln, Lwo
chemlcals assoclaLed wlLh drowslness (and, for LhaL maLLer, happlness). 8emember
Lhe MelaLonln LableL sold aL alrporLs Lo help Lravellers sleep? now you know also
why when some people are sLressed Lhey LA1! naLural SS8l !

Pence we feel Pappy afLer our Cn? reunlon dlnner. urlnklng Lea helps Lo keep us
awake. And we [usL wanL Lo slouch on Lhe sofa and slng or chlL chaL or 'chlll'

So whaL can Lhe med sLudenL or posL grad do Lo solve Lhls dllemma? Lasy. Clve me
Lhe food. l can afford Lo sleep!


71) on 8eta b|ockers and nypog|ycaem|a

uear ?ln Llng,
WhaL hypoglycemlc sympLom ls noL masked by beLa blockers?

Symptoms and S|gns of nypog|ycem|a
34(,1,5%&6
SweaLlng
leellng hoL
lns & needles
Shaklness
AnxleLy
alplLaLlons
7,81%(%9$6
ulfflculLy speaklng
Loss of concenLraLlon
urowslness
ulzzlness
Pemlplegla
ArrhyLhmlas, Selzures, Coma, ueaLh
:,1*;$&%0%&6
nausea
Punger
Weakness

Chor kuan:
1)8ecause of lLs ablllLy Lo mask auLonomlc sympLoms and suppress glycogenolysls,
beLa blockers musL be used wlLh cauLlon by dlabeLlc paLlenLs

2)llrsL, by blocklng beLa-1 recepLors, auLonomlc sympLoms are lnhlblLed. Among
Lhem ls Lachycardla, whlch normally serves as an early warnlng slgnal LhaL blood
glucose levels are falllng Loo low. (When glucose drops, Lhe sympaLheLlc nervous
sysLem ls acLlvaLed, causlng auLonomlc sympLoms)

3) Second, by blocklng beLa-2 recepLors ln muscle and llver, beLa-blockers suppress
glycogenolysls, Lhereby ellmlnaLlng an lmporLanL mechanlsm for correcLlng
hypoglycemla (whlch can occur when lnsulln dosage ls excesslve).

4) 8y masklng" Lhese auLonomlc sympLoms, beLa-blockers can delay awareness of
hypoglycemla, Lhereby compromlslng Lhe paLlenL's ablllLy Lo correcL Lhe problem ln
a Llmely fashlon.

3) 1herefore, paLlenLs should be LaughL Lo recognlse alLernaLlve slgns whlch are nC1
masked namely Lhe cogn|t|ve and non-spec|f|c s|gns (eg: hunger, faLlgue, poor
concenLraLlon, confuslon) LhaL blood glucose ls falllng dangerously low.

6) SWLA1lnC ls an excepLlon Lo Lhls. Slnce sweaLlng durlng acLlvaLlon of Lhe AnS ls
medlaLed by release of AceLylchollne vla acLlvaLlon of a nlcoLlnlc recepLor and nC1
8? nC8Au8LnALlnL vla an adrenerglc recepLor, sweaLlng may be one of Lhe only
slgns recognlsed by dlabeLlc paLlenLs on a beLa-blocker.


Pypoglycemla relaLed sympLoms ls seen ln paLlenLs who are elLher aware",
or have aLLenuaLed sympaLheLlc neural response (hypoglycemla unawareness) LhaL
can develop ln older paLlenLs, paLlenLs sufferlng from recurrenL hypoglycemla, glven
beLa blockers or Lhose wlLh dlabeLlc auLonomlc neuropaLhy.
ln paLlenLs who are hypoglycemlc aware, a fall ln blood glucose below 3.8 mM
resulLs ln an acuLe release of counLer-regulaLory hormones lncludlng glucagon &
noreplnephrlne. 1he release of noreplnephrlne resulLs from a CnS-medlaLed
sympaLheLlc dlscharge Lrlggered by hypoglycemla. 1he sympaLheLlc dlscharge
produces adrenerglc sympLoms produced by Lhe release of noreplnephrlne (and
posslbly by eplnephrlne release from Lhe adrenals) such as palplLaLlons, Lremor &
anxleLy.
Chollnerglc sympLoms such as sweaLlng & hunger occur from Lhe release of
aceLylchollne from sympaLheLlc posLgangllonlc (chollnerglc) neurons.
CognlLlve dysfuncLlon beglns Lo deLerloraLe when blood glucose falls Lo 3 mM. 1he
onseL of auLonomlc sympLoms ls lmporLanL because lL makes Lhe paLlenL aware of
Lhelr condlLlon & enables Lhem Lo Lake approprlaLe correcLlve acLlon before
cognlLlve lmpalrmenL occurs.
Powever ln paLlenLs who are hypoglycemlc unaware" Lhls early phase of
sympaLheLlc dlscharge (wlLh assoclaLed warnlng slgns) does noL occur unLll afLer
cognlLlve lmpalrmenL beglns, whlch lncreases Lhe llkellhood LhaL Lhey can become
severely hypoglycemlc.
1he Lhreshold for cognlLlve lmpalrmenL does noL change when paLlenLs develop
hypoglycemla unawareness.

8eLa-blockers should be used wlLh cauLlon (have a relaLlve conLralndlcaLlon") ln
dlabeLlcs because of Lhelr ablllLy Lo block Lhese sympaLheLlc lncreases and Lhus
make proper awareness more dlfflculL. Powever, lf a dlabeLlc paLlenL had suffered a
prevlous Ml, has CPl, or has a comblnaLlon of hyperLenslon and coronary arLery
dlsease, Lhe concern abouL Lhe poLenLlal beneflLs of beLa blocker Lherapy would
generally ouLwelgh Lhe concern abouL lLs affecLs Lo blunL reacLlons Lo hyperglycemla
ln mosL dlabeLlc paLlenLs.
noLe LhaL some responses Lo hypoglycemla (such as sweaLlng) would noL be blocked
by beLa blockers. 8ecause Chollnerglc sympLoms such as sweaLlng & hunger occur
from Lhe release of aceLylchollne from sympaLheLlc posLgangllonlc (chollnerglc)
neurons, beLa blockers do noL mask Lhese sympLoms!
kudos Lo baslc physlology!! ALL PAlL Lhe laLe rof 8aman!!

ln CCl, 8eLa blockers block beLa recepLors ln Lhe kldneys whlch leads Lo reducLlon of
8enln AngloLensln AldosLerone ouLpuL.
Choose beLa blockers wlLh no lSA acLlvlLy because Lhe parLlal agonlsL properLles
negaLes lLs beneflclal effecLs.
8lsoprolol belng a hlghly selecLlve beLa1 blocker has mlnlmal effecLs on lung
funcLlon ln asLhmaLlcs.
lL appears also Lo have no effecL on Pba1c ln dlabeLlcs.
ln paLlenLs wlLh Lvef of less Lhan 40 beLa1 selecLlve beLa blockers should be used.
8lsoprolol or Cardlvelol are Lhe drugs of cholce afLer opLlmlzaLlon of volume sLaLus
and successful dlsconLlnuaLlon of lv dlureLlcs.
SLarL LCW and CC SLCW ln upLlLraLlon.
at|ents w|th CCI |n ear|y stages d|e from arrthym|as at home, beta1 se|ect|ve
b|ockers reduce that r|sk.
In advanced CCI A1ILN1S d|e from pump fa||ure

72) on 1r|g|ycer|des and DM
Dear |n L|ng,
I gr|||ed the students of causes of hypertr|g|ycer|daem|a and many have no |dea!
Always Lhlnk of Alcohollsm and ulabeLes when seelng paLlenLs wlLh Plgh 1C whlch ls
very2 common. MeLabollc syndrome seen ln 32.2 of adulL Mslans!
Plgh 1C conLrlbuLe Lo resldual rlsk even afLer sLaLln 8x

lnsulln reslsLance causes release of llA fr Lhe llver. 1hls ls assoclaLlon wlLh hlgh 1C,
PlCP SMALL LuL and low PuL levels. 1C causes small dense LuL parLlcles Lo lncrease
and Lhese are hlghly aLherogenlc
LuL parLlcle numbers lncrease wlLh lncreaslng 1C

LCW LuL LLvLLS Anu LCW LuL A81lCLL nuM8L8S MLAnS LCW 8lSk
PlCP LuL LLvLLS 8u1 LCW LuL A81lCLL nuM8L8S lS ALSC LCW 8lSk!!!

Low carbo, frucLose and sugar lnLake ls key Lo 1C reducLlon.
llbraLes makes small dense LuL 8LCCML 8lC LLSS uLnSL LuL.

We are noL able Lo rouLlnely measure LuL3 Lhe small dense LuL.
Su88CCA1L llnulnCS Cl PlCP 1C, LCW PuL Anu PlCP LuL lMLlLS PlCP LuL3
WlLh llbraLes 8x we see small rlse ln PuL and mark drop ln 1C. 1hls suggesLs LhaL
desplLe no change ln LoLal LuL LLvLLS, 1PL LuL3 lS LLSS Anu LuL1 MC8L. LuL1 ls
blgger and less uLnSL

A r|se |n ost rand|a| 1G |s the ear||est |nd|cat|on of |mpend|ng DM!

ln Malaysla, ln 2011 for Lhose more Lhan 18yrs, Lhe prevalence was 13
lor Lhose more Lhan 30yrs old, lL was a shocklng 20.
no dlfference beLween rural and urban popn!
Pence a Lerrlfylng slLuaLlon exlsLs whereby we drs musL sLarL acLlng fasL.

1he eplc cenLre of uM ls now ln Asla.
Aslans dev uM younger and aL lower bml!
osL prandlal hyperglycaemla...... lsolaLed lC1 reflecLs a hlgh rlsk of uM!

We eaL loLs of 8lce... even Lhe normal non dlabeLlc Chlnese have a much hlgher area
under Lhe glucose curve posL prandlally cf Lo caucaslans.
Aslans who are dlabeLlcs are MC8L LlkLL? Lo dev esrf.
lndlan dlabeLlcs have Lhe hlghesL rlsk of lPu

We need Lo screen ?CunCL8 A1lLn1S Anu A1 LCWL8 8Mls
SLarL aL 30yrs. And waLch for renal lmpalrmenL early.
We need a culLural change Lo eaL less carbos,, less rlce.
And we should cease Lo greeL each oLher wlLh.... "have you eaLen?" 8uL "have you
exerclsed?"


73) on D|ppers

uear yln llng,
Are you aware LhaL Lung luncLlon also has a dlurnal varlaLlon, lL ls WC8SL aL 4am
and 8esL aL 4pm!

now do you know why asLhmaLlcs and CCu paLlenLs go WPPLLLLL when Lhe PC
[usL abouL enLers 8LM sleep?
Larly mornlng "1lghLness" ls an lmporLanL quesLlon Lo ask as some paLlenLs do noL
wheeze.
uo you wake up aL nlghL ls anoLher lmporLanL quesLlon.... lLs noL [usL hearL fallure
LhaL causes nu!!

Pow good ls your paLlenL's asLhmaLlc conLrol??
If he uses MCkL than 1 re||ever |nha|er A LAk, h|s contro| |s NC GCCD!
Cood conLrol ls when a paLlenL uses nC1 MC8L Lhan or Lqual Lo merely 2 puffs a
week, hence 32 x 2 = 104 puffs an Ln1l8L ?LA8! A slngle Mul ls more Lhan sufflclenL
for Lhls.
ln general, 80 of paLlenLs wlLh asLhma are nC1 well conLrolled.

1he use of a sLerold lnhaler as prevenLer alone has Lhe ulsadvanLage LhaL Lhe paLlenL
uoes nC1 feel beLLer, hence compllance ls poor. aLlenLs wlll only Lake medlclnes
whlch makes Lhem leel 8eLLer no maLLer how much we Lalk!
Pence a ComblnaLlon of a LA8A+SLerold has an advanLage here. noL only ls Lhe
lnhaled sLerold whlch ls all lmporLanL dellvered, Lhe paLlenL feels a dlfference and ls
psychologlcally convlnced LhaL he ls uslng a "good" medlclne.
SLerold lnhalaLlon ls Lhe bedrock of asLhma LreaLmenL for any acuLe eplsode of
asLhma 8LCL1S more asLhma!

Lxacerbat|on |s furthermore assoc|ated w|th LCSS CI LUNG IUNC1ICN!
AsLhma ls llke ulabeLes and PyperLenslon, a CP8CnlC dlsease whlch causes more
and more damage. Whlle we had over decades of hard work convlnced paLlenLs on
Lhe need Lo LreaL uM and P1 Lo prevenL lLs Lerrlble compllcaLlons, Many uocLors,
medlcal sLudenLs and aLlenLs are nC1 even aware LhaL AsLhma lf unconLrolled wlll
acceleraLe Lhe loss of lung funcLlon.
Many are aware that CCD |s assoc|ated w|th progress|ve deter|orat|on of Lung
funct|on but now p|s know that SC IS AS1nMA when uncontro||ed!
Cnly lnhaled sLerolds can 8lunL Lhls effecL.

As we age we loose Lung luncLlon progresslvely, Lyplcally abouL 20 ls losL by Lhe
age of 80 years ln a non Smoker sLaylng ln a non polluLed place. Pere wlLh all our
second hand smoke, smog and CC and CC2, lL ls worse!
Many asLhmaLlcs 8LCCML CCu llke paLlenLs as Lhelr lung funcLlon deLerloraLe.
Pave l noL screamed myself hoarse aL bedslde abouL Lhe 3 clrcles of AsLhma, Lhe ln
8eLweens and CCu!?

Many CCD pat|ents w|th NC h|story of smok|ng or cook|ng w|th f|rewood may
have had poor|y contro||ed asthma |n the|r younger years.
Lven wlLh relaLlvely well asLhmaLlc paLlenLs wlLh mlnlmal sympLoms nC1 on
LreaLmenL wlLh lnhaled sLerolds, alrway blopsles have shown perslsLenL eoslnophllllc
lnfllLraLlon. 1hls leads Lo progresslve lnflammaLlon and desLrucLlon. lnhaled sLerolds
has been shown Lo prevenL Lhls.
Lvldence does nC1 supporL Lhe use of an lnhaled sLerold ALCnL or Lhe use of
lnhaled rellever alone even wlLh so called "well conLrolled" asLhmaLlcs. A
comblnaLlon of LA8A plus a sLerold ls sLlll beLLer. ComblnaLlon ls beLLer Lhan elLher
componenL medlcaLlon used slngly. 1he luA however does noL agree buL LhaL ls
anoLher sLory!


74) on G|ucosam|ne and G|ngko

Dear |n L|ng,

Many pat|ents take G|ucoasam|ne for [o|nt d|sorders. Are you aware of any
dangers assoc|ated w|th |t?

lrom Medscape:
Clucosamlne supplemenLaLlon was llnked Lo slgnlflcanL, reverslble lncreases ln
lnLraocular pressure (lC) ln a small, reLrospecLlve sLudy publlshed onllne May 23 ln
!AMA CphLhalmology.
lrequenLly, paLlenLs are belng Lold LhaL whlle sLudles glve confllcLlng daLa as Lo
wheLher glucosamlne and chondrolLln sulfaLe are effecLlve ln reduclng arLhrlLlc paln,
Lhere does noL appear Lo be any rlsk ln Lrylng Lhese supplemenLs.
uS prevalence of osLeoarLhrlLls ls 27 mllllon, and for open-angle glaucoma, lL
exceeds 2 mllllon, accordlng Lo Lhe CenLers for ulsease ConLrol and revenLlon.
AlLhough lL ls unclear whaL Lhe lmpllcaLlons of havlng lncreased lC would be for
lndlvldual paLlenLs, Lhe rlsk ls LhaL ocular damage could posslbly occur from whaL
were prevlously LhoughL Lo be 'benlgn' supplemenLs.

?ln Llng,
you know of folks who Lake Clngko ln hopes of boosLlng Lhelr memory" or even
prevenLlng Alzhelmer's (and Lhe laLLer ls noL Lrue as sLudles show Clngko does noL
prevenL Alzhelmer's dlsease) . now Lhere ls more daLa Lo suggesL cauLlon before you
declde Lo Lake Clngko.
1he flrsL uS governmenL Loxlcology sLudy of glnkgo blloba found LhaL Lhe exLracL
caused cancer ln lab anlmals, lncludlng an excesslve number of llver and Lhyrold
cancers, as well as nasal Lumors.
1he flndlngs were somewhaL surprlslng because glnkgo blloba has had a long and
apparenLly benlgn hlsLory of human use. AlLhough lL has been assoclaLed wlLh
bleedlng and cerebral hemorrhages ln Lhe elderly, Lhere have generally been few
reporLs of serlous slde effecLs.

1he resulLs of Lhe sLudy do noL conflrm LhaL glnkgo blloba ls dangerous Lo humans,
buL lL ls dlsLurblng LhaL Lhe laboraLory anlmals all Lended Lo suffer Lhe same sorLs of
ln[urles. 1he sLudy concluded LhaL Lhere ls clear evldence LhaL glnkgo causes
carclnogenlc acLlvlLy ln Lhe llvers of mlce and some evldence llnklng lL Lo
carclnogenlc acLlvlLy ln raLs' Lhyrolds.
llndlngs ln anlmal sLudles may noL necessarlly LranslaLe Lo humans buL neverLheless
lL ls dlsLurblng Lo know LhaL Clngko has carclnogenlc acLlvlLy.
8efore you lngesL any herb, always ask yourself
- whaL are Lhe proven beneflLs?
- whaL ls Lhe poLenLlal harm?
lf ln doubL, uCn'1





7S) on re nypertens|on

Dear |n L|ng,

If I am to ask you to comment on th|s, what w||| you say?

1hls ls llke geLLlng engaged buL noL marrled, quesLlon ls, A8L ?Cu ln 8lC 18Cu8LL
C8 A8L ?Cu nC1?
Can you geL ouL of Lhe mess or are you sLuck!?
1he dlagnosls was lnvenLed ln May 2003
Systo||c 120 to 139
D|asto||c 80 to 89
8ased on M8ll1 Lhere ls a conLlnuous lncrease ln rlsk as bp rlses
lf Lhere ls re uM, why noL re P1?
CpLlmal bp ls less Lhan 120 80
Annual morLallLy raLe for Lhose wlLh re P1 ls more Lhan 3 Llmes LhaL of a normal
person. nPAMLS
Cver 4 yrs, converslon of re PpL Lo PpL ln Lhe elderly ls more Lhan 30
rogresslon ls fasL, almosL 60 by 4 yrs
re PpL ls less ln Lhose more Lhan 60yrs as mosL have 8CC8LSSLu 1C P1!
reva|ence |s 37 |n ms|a! MCkL CCMMCN IN MALLS
Worldwlde 8LvALLnCL ls 38
8lslng obeslLy ls assoclaLed wlLh re PpL
re PpL ls assoclaLed wlLh lnsulln reslsLance
Lv mass ls hlgher ln re PpL
re npt 27 |ncrease |n a|| cause morta||ty
And
66 |ncrease |n cvs morta||ty
ManagemenL. WL reducLlon, salL reducLlon, sLress managemenL, buL reducLlon ls noL
susLalnable wlLh Llme.

WL loss ls besL
SalL reducLlon ls second besL
urugs?? uo we LreaL one Lhlrd of Lhe enLlre adulL populaLlon??
no ouLcome daLa lf re PpL ALCnL!
8u1 Lrlals have shown LhaL we shd LreaL when Lhere are oLher rlsk facLors or when
rlsk scores are hlgh.
Look for LargeL organ damage, lf so 18LA1!
1he younger Lhe paLlenL, Lhe more vlgllanL Lhe search for secondary causes.
1. Conflrm Lhe Plgh 8
2. Search for underlylng causes
3. Search for 1argeL organ damage
8emember "Plgh 8 causes damage!"

76) on the So||tary u|monary nodu|e

Dear |n L|ng,

1h|s f|nd|ng |s worry|ng for both doctor and pat|ent. now do you approach th|s
d|agnost|c prob|em?

More Lhan half of all sollLary pulmonary nodules are benlgn. 8enlgn nodules have
many causes, lncludlng old scars and lnfecLlons. lL ls surrounded by normal lung
Llssue and ls noL assoclaLed wlLh any oLher abnormallLy ln Lhe lung or nearby lymph
nodes
lnfecLlous granulomas (reacLlons Lo a pasL lnfecLlon) cause mosL benlgn leslons.
Common lnfecLlons LhaL lncrease Lhe rlsk for developlng a sollLary pulmonary nodule
lnclude:
1uberculosls
Lung dlseases caused by a fungus
Lung cancer pr|mary or secondary |s the most common cause of cancerous
(ma||gnant) pu|monary nodu|es. Approx|mate|y 20-30 of a|| cases of |ung cancer
appear as So||tary Nodu|es on chest k-ray f||ms. 1herefore, the goa| of
|nvest|gat|ng |s to d|fferent|ate a ben|gn growth from a ma||gnant growth as soon
and as accurate|y as poss|b|e.
lL should be consldered poLenLlally cancerous unLll proven oLherwlse.
A sollLary pulmonary nodule ls mosL ofLen found on a chesL x-ray or a chesL C1 scan,
whlch are ofLen done for oLher sympLoms or reasons.
1he cllnlcal declslon ls wheLher Lhe nodule ln lung ls probably benlgn. 1hls ls more
llkely lf:
1he nodule ls small, has a smooLh border, and has a solld and even appearance on
an x-ray or C1 scan
aLlenL ls young and do noL smoke
We may Lhen choose Lo [usL waLch Lhe nodule on x-rays ln 2 mLhs.
Age: 8lsk of mallgnancy lncreases wlLh age.
8lsk of 3 aL age 33-39 years
8lsk of 13 aL age 40-49 years
8lsk of 43 aL age 30-39 years
8lsk of greaLer Lhan 30 ln persons older Lhan 60 years.
at|ents who have an o|der chest k-ray f||m has a go|dm|ne for compar|son. 1h|s |s
|mportant because the growth rate of a nodu|e can be ascerta|ned. 1he doub||ng
t|me of most ma||gnant Nodu|es |s 1-6 months.
8epeaL chesL x-rays or chesL C1 scans are Lhe mosL common way Lo follow Lhe
nodule. lf Lhe C1 scan demonsLraLes faL wlLhln Lhe nodule, Lhe leslon ls llkely benlgn,
hamarLoma. nowadays lung L1 scans may be done. MallgnanL cells have a hlgher
meLabollc raLe Lhan normal cells and benlgn abnormallLles, Lherefore, Lhe glucose
upLake of mallgnanL cells ls hlgher. oslLron emlsslon Lomography (L1) lnvolves
uslng a radlolabeled subsLance Lo measure Lhe meLabollc acLlvlLy of Lhe abnormal
cells. MallgnanL nodules absorb more of Lhe subsLance Lhan benlgn nodules and
normal Llssue and can be readlly ldenLlfled on Lhe 3-dlmenslonal, colored lmage.
L1 scan ls an accuraLe, nonlnvaslve exam, buL Lhe procedure ls expenslve.
lf repeaLed x-rays show LhaL Lhe nodule slze has noL changed over 2 years, lL ls mosL
llkely benlgn and a blopsy ls noL needed.
ersons who have been cllnlcally dlagnosed wlLh a benlgn nodule should schedule
Lhe recommended follow-up, as follows:
ChesL x-ray fllms should be Laken every 3 monLhs for Lhe flrsL 12 monLhs and Lhen
every 6 monLhs for Lhe followlng 12 monLhs.
AfLer Lhls 2-year perlod, Lhe nodule may be observed yearly for up Lo 3 years.
We may choose Lo blopsy Lhe nodule Lo rule ouL cancer lf:
?ou are a smoker
?ou have oLher sympLoms of lung cancer
1he nodule has grown ln slze or has changed compared Lo earller x-rays.
A Lransbronchlal needle asplraLlon (18nA) blopsy may be done lf Lhe nodule ls close
Lo Lhe alrway.
1ransLhoraclc needle asplraLlon (11nA) blopsy: 1hls Lype of blopsy ls used lf Lhe
leslon ls noL easlly accesslble on Lhe alrway wall or ls smaller Lhan 2 cm ln dlameLer.
lf Lhe Sn ls on Lhe perlphery of Lhe lung, a blopsy sample has Lo be Laken wlLh Lhe
help of a needle lnserLed Lhrough Lhe chesL wall and lnLo Lhe Sn. lL ls usually
performed wlLh C1 guldance.
WlLh Sns larger Lhan 2 cm ln dlameLer, Lhe dlagnosLlc accuracy ls hlgher (90-93).
Powever, Lhe accuracy decreases (60-80) ln nodules LhaL are smaller Lhan 2 cm ln
dlameLer.


77) on 8|ess|ngs

Dear |n L|ng,

Are you aware of Lhe ulfferenL klnd of 8lesslngs?
1he U|nar 8|ess|ng:
An ulnar claw ls an abnormal hand poslLlon LhaL develops due Lo a leslon wlLh Lhe
ulnar nerve. A hand ln ulnar claw poslLlon wlll have Lhe rlng and llLLle flngers drawn
Lowards Lhe back of Lhe hand aL Lhe M!olnL and curled Lowards Lhe palm aL Lhe l
and ul when the f|ngers are extended.
8emember Lhe acLlon of Lhe Lumbrlcals!? WhaL ls Lhe LAS1 muscle used ln Lhe acL of
MALL MlcLurlLlon?!! 1he medlal Lwo lumbrlcals are noL worklng due Lo ulnar
damage, Lhe 3rd & 4Lh lumbrlcals are unable Lo exLend Lhe l & ul [olnLs aL Lhe
4Lh & 3Lh dlglLs, so Lhe medlal Lwo dlglLs are clawed, clawlng ls caused by exLenslon
of M [olnL by LxLensor dlglLorum and flexlon caused by llexor dlglLorum..
1he ulnar nerve conLrols Lhe 3rd & 4Lh lumbrlcals, Lhe Lhree hypoLhenar muscles,
Lhe dorsal & palmar lnLerossel, Lhe palmarls brevls and Lhe adducLor polllcls. ulnar
nerve damage may also cause hypoLhenar aLrophy.


1he u|nar c|aw can presenL as a "hand of benedlcLlon" or "pope's blesslng".

Powever, Lhe Lerm "hand of benedlcLlon" or "pope's blesslng" also commonly refers
Lo a slmllar hand poslLlon whlch ls caused by damage Lo Lhe medlan nerve and ls
only presenL when Lhe paLlenL ls asked Lo ........ make a f|st!!
Pence sLudenLs are ofLen confused because of Lhese dlfferenL 8lesslngs!!
A d|fferent hand of bened|ct|on resu|ts from |n[ury of the Med|an nerve:
1he pope's hand ls seen wlLh medlan nerve dysfuncLlon when asklng Lhe paLlenL Lo
make a flsL due Lo lnablllLy Lo flex 1sL & 2nd flngers aL l. 1he medlan nerve
conLrols Lhe 1sL & 2nd lumbrlcals, Lhree Lhenar muscles (abducLor polllcls brevls,
flexor polllcls brevls, and vla a dlsLal branch Lhe opponens polllcls). AddlLlonally
Lhere may be Lhenar aLrophy.
1he exLensor dlglLorum ls lefL unopposed and Lhe meLacarpophalangeal [olnLs of
lndex and mlddle flngers remaln exLended whlle aLLempLlng Lo ..... make a flsL.

1herefore ln medlan nerve ln[ury, Lhere wlll be 8LnLulC1lCn slgn when maklng a
llS1....buL nC benedlcLlon slgn when flngers are Lx1LnuLu!!
Medlcal sLudenLs musL flrsL undersLand Lhe ALL lMC81An1 CuesLlon Lhe laLe
rofessors of AnaLomy used Lo ask us: WhaL ls Lhe lasL muscle used ln Lhe acL of
MALL mlcLurlLlon? and all ls crysLal clear! So flrsL undersLand Lwo lmporLanL
concepLs: 1) 1he lumbrlcals and whaL Lhey do. 2) ls Lhe paLlenL belng asked Lo
exLend Lhelr flngers or make a flsL?
1he Lumbrlcals are responslble for flexlng Lhe MC and exLendlng Lhe l and ul
[olnLs. 1he Medlan nerve conLrols Lhe lumbrlcals for Lhe lndex and Mlddle flngers.
1he ulnar nerve conLrols Lhe lumbrlcals for Lhe rlng and llLLle flngers.
1herefore lf Lhe lumbrlcals don'L work Lhen we have Lhe opposlLe: exLended MC
and flexed l and ul.


...................................
1o a|| the y|n ||ngs out there |n th|s cyber tutor|a| room,
ln concluslon,
As l leave Lhe sLage,
Lxamlne from head Lo Loe
8efore you dare dlagnose
More harm ls done
8ecause you dld noL look
1han from noL knowlng whaL's ln Lhe book
Above all do noL be hasLy proud and spoL
8ecause you Lhlnk you know a loL
1he greaL cllnlclans may aL one look know
8uL Lhen you do noL know
1he greaL blLLer lessons Lhey humbly swallowed
So be dlllgenL and safe
A meLlculous groom Lo Lhe paLlenL brlde.


lease reallse LhaL Lhe sLudy of cllnlcal medlclne ls unllke any oLher schoollng you
have gone Lhrough before. Pere you are called on, you are asked a quesLlon, you
answer lL. 1haL ls why l ask so many CuesLlons.

Why don'L Lhe bedslde Leachers [usL glve you a lecLure? 8ecause Lhrough Lhe
quesLlons, you learn Lo Leach yourselves. 8y Lhls meLhod of quesLlonlng-answerlng,
quesLlonlng-answerlng, we seek Lo develop ln you Lhe ablllLy Lo analyze LhaL vasL
complex of facLs LhaL consLlLuLes Lhe relaLlonshlps beLween healLh and lllnesses.

lor Lhe resL of your earLhly llfe as a docLor unLll you [oln PlppocraLes, Csler and Pwa
1uo ln CC dlscusslons, you wlll be deallng wlLh CuesLlons posed Lo you! WhaL does
Lhls sympLom, Lhls slgn, Lhls lllness mean? WhaL does Lhls lab reporL lmply?

now, you may Lhlnk, aL Llmes, LhaL you have reached a correcL and flnal answer. ?ou
are assured LhaL Lhls ls a deluslon on your parL, Lhere ls always anoLher quesLlon,
Lhere ls always a quesLlon Lo follow your answer. ?es, you are on a Lreadmlll. Look aL
your senlors pracLlslng medlclne for many years, do you noL see Lhls endless
Lreadmlll we walk on? As soon as we Lhlnk we have solved one paLlenL's puzzle, 10
more appear, eL lnflnlLum. 8y Lhls Lralnlng process we hope Lo prepare you for Lhe
real world of crowded wards and endless cllnlcs.

1he cllnlcal quesLlons spln Lhe Lumblers of your braln. ?ou are on an operaLlng Lable,
Lhe quesLlons are flngers problng your mlnd, urglng you Lo Lhlnk clearly and
raLlonally. We do braln surgery here. ?ou Leach yourselves Lhe facLs of medlclne and
we Lraln your mlnds Lo Lhlnk llke a docLor. 1he lacLs of Medlclne ls Lhe SClLnCL of
medlclne, Pow Lo Lhlnk llke a compeLenL docLor ls Lhe A81 of medlclne. ?ou need
boLh.


1o my be|oved Med|ca| students,
p|s |earn the Art of D|agnos|s and deduct|on we||.
1hls ls an arL whlch can only be acqulred by long and paLlenL sLudy, nor ls llfe long
enough Lo allow any morLal Lo aLLaln Lhe hlghesL posslble perfecLlon ln lL. And we
begln by masLerlng more elemenLary problems.

?ou should conslder your braln as llke an empLy sLoreroom, and you have Lo sLock lL
wlLh goods as you choose. A fool Lakes ln all LhaL he comes across, so LhaL Lhe
knowledge whlch mlghL be useful Lo hlm geLs crowded ouL, or aL besL ls [umbled up
wlLh a loL of oLher Lhlngs, so LhaL he has dlfflculLy ln laylng hls hands upon lL. 1oo
much M3s, k1vs, Candy Crush does exacLly Lhls 8u1 Lhe skllled cllnlclan ls very
careful lndeed as Lo whaL he Lakes lnLo hls sLoreroom. Pe wlll have noLhlng buL Lhe
Lools whlch may help hlm ln dolng hls work, buL of Lhese he has a large assorLmenL
and all ln Lhe mosL perfecL order. lL ls a mlsLake Lo Lhlnk LhaL LhaL Lhls llLLle room has
elasLlc walls and can dlsLend Lo any exLenL. uepend upon lL Lhere comes a Llme
when for every addlLlon of knowledge good, bad or useless, you forgoL someLhlng
LhaL you knew before. lL ls of Lhe hlghesL lmporLance, Lherefore, noL Lo have useless
facLs elbowlng ouL Lhe useful ones.

Always approach a paLlenL wlLh an absoluLely blank mlnd, whlch ls always an
advanLage. lorm no Lheorles before hand, and afLer a compeLenL hlsLory observe
meLlculously and Lhen only draw lnferences from your observaLlons.
PlsLory
MosL people, lf you descrlbe a Lraln of evenLs Lo Lhem, wlll Lell you whaL Lhe resulLs
would be. 1hey can puL Lhose evenLs LogeLher ln Lhelr mlnds, and argue from Lhem
LhaL someLhlng wlll come Lo pass. 1here are a few people, however, who, lf you Lold
Lhem a resulL, would be able Lo evolve from Lhelr own lnner consclousness whaL Lhe
sLeps were whlch led up Lo LhaL resulL. 1hls ablllLy Lo work backwards and see Lhe
naLural hlsLory of Lhe lllness ln lLs enLlreLy ls essenLlal Lo a dlagnosLlclan. When we
see Lhe enLlre sequence of evenLs rlghL from Lhe sLarL even Lhough Lhe paLlenL may
have presenLed Lo us now 6 monLhs lnLo Lhe dlsease when a flnal sLraw leL hlm Lo
you, you wlll see Lhe dlagnosls.
1here ls no sLep ln dlagnosls Loday whlch ls so lmporLanL and so much neglecLed as
Lhe arL of Lraclng Lhe enLlre naLural hlsLory of Lhe lllness from Lhe beglnnlng.
SLudenLs Loday slmply have forgoLLen Lhls cruclal sLep. Always lay greaL sLress upon
lL, and pracLlce lL Llll lL becomes second naLure.
lL ls a caplLal mlsLake Lo Lheorlze before you have all Lhe evldence.
lnsenslbly, one beglns Lo LwlsL Lhe physlcal slgns Lo sulL Lheorles, lnsLead of Lheorles
Lo sulL whaL ls seen. lL blases Lhe [udgmenL.
1he LempLaLlon Lo form premaLure Lheorles upon lnsufflclenL daLa ls Lhe bane of Lhls
noble professlon.
hyslcal LxamlnaLlon
1o a greaL mlnd, noLhlng ls llLLle. A llLLle spllnLer haemorrhage means much Lo an
asLuLe cllnlclan. LeL hlm on flrsL seelng a paLlenL learn Lo sharpen Lhe faculLles of
observaLlon, where Lo look and whaL Lo look for. 8y a man's flnger-nalls, by hls
hands, by hls eyes, by hls shlns, by Lhe calloslLles of hls feeL, by hls expresslon, eLc -
by each of Lhese Lhlngs a dlsease' slgnaLure ls plalnly revealed. 1haL all unlLed should
fall Lo enllghLen Lhe compeLenL lnqulrer ln any case ls almosL lnconcelvable.
never LrusL Lo general lmpresslons, buL concenLraLe yourself upon deLalls.
?our meLhod should be founded upon Lhe observaLlon of Lrlfles.
ulagnosls
1he mosL commonplace lllnesses when lL presenLs ln an uncommon manner ls ofLen
Lhe mosL mysLerlous, because Lhe mlnd belng dogmaLlc falls and no deducLlons may
be drawn. 8emember LhaL a Common lllness wlLh an unconvenLlonal presenLaLlon ls
far more common Lhan a 8are dlsease ln lLs common presenLaLlon. 1hlnk of our Cld
frlends llrsL!
never guess. lL ls a shocklng hablL - desLrucLlve Lo Lhe loglcal faculLy.
Cbserve Lhe small facLs upon whlch large lnferences may depend.
When you have ellmlnaLed Lhe lmposslble, whaLever remalns, however lmprobable,
musL be Lhe LruLh.
ln maklng your rovlslonal ulagnosls, always look for posslble alLernaLlves, your
ulfferenLlal ulagnosls, and provlde for and agalnsL lL. 1he LruLh ls only arrlved aL by
Lhe palnsLaklng process of ellmlnaLlng Lhe unLrue.
lL should be your buslness as a medlcal sLudenL Lo know Lhlngs. 1o Lraln yourself Lo
see whaL oLhers overlook.
1o carry Lhe arL, however, Lo lLs hlghesL plLch, lL ls necessary LhaL Lhe docLor should
be able Lo uLlllze all Lhe facLs whlch have come Lo hls knowledge, and Lhls ln lLself
lmplles, as you wlll readlly see, a possesslon of all knowledge, whlch, even ln Lhese
days of lnLerneL and smarLphones, ls a somewhaL rare accompllshmenL.
neverLheless we should possess as much knowledge as posslble whlch ls llkely Lo be
useful Lo our work.

A man should keep hls llLLle sLoreroom sLocked wlLh all Lhe furnlLure LhaL he ls llkely
Lo use, and Lhe resL he can puL away ln Lhe garage, where he can geL lL lf he wanLs lL.
8ead noLhlng buL Lhe medlcal news and Lhe sLandard LexLs.

1he mosL pracLlcal Lhlng LhaL you ever can do ln your llfe would be Lo balance lL
beLween Lhe wards and Lhe annals of medlclne. LveryLhlng comes ln clrcles. 1he old
wheel Lurns, and Lhe same spoke comes up. lllnesses had come before, and wlll be
agaln. 1hen when you have heard some sllghL lndlcaLlon of Lhe course of evenLs ln a
paLlenL, you should be able Lo gulde yourself by Lhe scores of oLher slmllar cases
whlch should occur Lo your memory.

When you are sLuck, you should puL yourself ln your Leacher's place, and Lry Lo
lmaglne how he would proceed under Lhe same clrcumsLances.
lL ls of Lhe hlghesL lmporLance ln Lhe arL of dlagnosls Lo be able Lo recognlze, ouL of a
number of facLs, whlch are lncldenLal and whlch vlLal. 8uL
make lL a polnL of never havlng any pre[udlces, and of followlng docllely wherever a
facL may lead you.
LducaLlon never ends. lL ls a serles of lessons wlLh Lhe greaLesL for Lhe lasL.


WnA1 MLDICAL 1eachers MAkL

AL a soclal funcLlon, a group of professlonals were slLLlng around Lhe dlnlng Lable
chlL chaLLlng. A buslnessman declded Lo explore Lhe problem of Lhe poor pay of
Leachers. Pe reasoned,
"llrsLly, how much can one MAkL as a Leacher? ?ou need Lo mark assessmenLs,
Leach spollL prlvlleged klds, flll a hundred admlnlsLraLlve forms Lo be flnanclally [usL
above Lhe waLer. Pow much can one make as a docLor Leachlng medlcal sLudenLs?
?ou guys musL be a really self sacrlflclng loL or be born lnLo wealLh Lo do all Lhese".

"8e honesL. WhaL do you make from Leachlng?"
sllence......

1he medlcal school LuLor answered "?ou really wanL Lo know whaL l make? l may be
very sLrlcL walklng around wlLh a cane ln my hand 8u1 l make young mlnds work
harder Lhan Lhey ever LhoughL Lhey could. l show Lhem LhaL Lhere ls no llmlL Lo Lhelr
deLermlnaLlon Lo be good.

l mesmerlze resLless young boys and glrls Lo slL ln awe Lhrough 120 mlnuLes of
Lhlnklng skllls on dlagnosls and paLlenL care when Lhelr aLLenLlon span used Lo be no
more Lhan 20mlns..
l make Lhem amazed aL Lhe beauLlful arL of cllnlcal dlagnosls.
l make Lhem quesLlon Lhemselves on every declslon Lhey make as Lo wheLher lL ls
Lhe besL for Lhe paLlenL.
l make Lhem reallse LhaL every lllness has a 8eal human face behlnd lL, Lhey are
paLlenLs nC1 cases.
l Leach Lhem Lo have respecL for Lhelr peers and Leachers.
l make Lhem feel LhaL all of Lhem can be greaL docLors lf Lhey wanL Lo.
l make Lhem read, read, read Lhe sclence of medlclne.
l make Lhem feel lL ls worLh Lhelr whlle Lo sacrlflce daLes and parLles for Lhelr
educaLlon.
l make sLudenLs feel proud Lo wear a whlLe coaL and Lo be ln Lhe llneage of a greaL
and noble professlon.
l make Lhem happy Lo be ln Lhe mldsL of wards of human sufferlng, learnlng Lo care
and relleve.

llnally, l make Lhem undersLand LhaL lf Lhey use Lhelr lnLellecL, work hard, and
follow Lhelr hearLs, Lhey can all succeed ln llfe, for success ls nC1 necessarlly
measured ln dollars and cenLs, buL ln how much we can help our fellow men. l Leach
Lhem LhaL Lhey musL nLvL8 be Wallpapers sLaylng on Lhe frlnge of socleLy buL lead,
care and help socleLy".

"And when people enqulre whaL l make, l can hold my head up hlgh ... and Lell Lhem
LhaL

l MAkL A ulllL8LnCL. now whaL do you make?"
LeL us noL forgeL our duLy as docLors as sLaLed ln Lhe PlppocraLlc CaLh Lo pass on our
skllls and knowledge Lo Lhe nexL generaLlon, and Lo LreaL Lhose who LaughL us Lhls
arL as our parenLs!


CSLLk-ISM
uear ?ln Llng, 14
Lh
March 2014

l asked for Csler's help and he replled LhaL 1lme ManagemenL ls essenLlal for
successful posL graduaLe sLudles (and of course undergraduaLe as well).
1he good physlclan Csler urged seLLlng deflnlLe goals, here for you ls arL 2A of
M8C, whlle meLhodlcally plannlng each day.

1hrough hls concepL of day-LlghL comparLmenLs," Csler sald Lo worry less abouL Lhe
pasL or Lhe fuLure, buL lnsLead focus on Lhe presenL. Pe agaln resonaLes wlLh Lhe
8uddhlsL Leachlng of Mlndfulness of Lhe presenL momenL. Pls meLhod was Lo seL
aslde speclflc hours of each day for wrlLlng, (ln your case SLudylng) whlch ls
sacrosancL, nC1PlnC, nC CnL can dlsLurb Lhose preclous hours, whlle belng sure
LhaL he also had Llme for hls lnLerpersonal relaLlonshlps (whlch ln your case ls Lhe
ulnner wlLh my famlly almosL akln Lo Lhe essenLlal dlnners LhaL lawyers have Lo
parLlclpaLe ln aL Lhe lnns of Law).


uear ?ln Llng, 16
Lh
March 2014

1o succeed ln your quesL, Csler sald LhaL you musL llnd MenLors, boLh dead and
allve. Csler hlmself soughL many menLors ln hls llfe and ln LrlbuLe, dedlcaLed hls
mosL celebraLed book, 1he rlnclples and racLlce of Medlclne, Lo Lhree of Lhem.

Pe was a serlous sLudenL of many greaL wrlLers. ln addlLlon Lo Lhelr sLudles, hls
sLudenLs were urged Lo read for half an hour each day from good phllosophlcal
works. ?our 1hursday nlghL classes are essenLlal!

ln addlLlon, Csler had hlsLorlcal menLors long dead who lnsplred hlm by Lhelr llves
and work and Lhey lncluded Wllllam Parvey (1378-1637), and 1homas Sydenham
(1624-1689). Csler soughL opporLunlLles Lo surround hlmself wlLh medlcal sLudenLs.
1hey were frequenLly lnvlLed Lo parLake ln meals aL hls home ln 8alLlmore.

Csler looked Lo sLudenLs Lo sLlmulaLe hlm and serve as an anLldoLe agalnsL
premaLure senlllLy. 1hese relaLlonshlps were naLurally muLually beneflclal.



uear ?ln Llng, 17
Lh
March 2014

Csler sald Lo Lell you Lo 8e oslLlve!!

Pe hlmself was, by all accounLs, an opLlmlsL.
ln AequanlmaLus," Csler urged medlcal sLudenLs Lo choose Lhelr paLh and declde
whaL Lype of docLor Lhey were Lo be. Pe belleved LhaL we could creaLe our own
fuLure and declde whaL Lype of llfe we may llve. 1o each one of you Lhe pracLlce of
medlclne wlll be very much as you make lL-Lo one a worry, a care, a perpeLual
annoyance, Lo anoLher, a dally [oy and a llfe of as much happlness and usefulness as
can well fall Lo Lhe loL of man."

See, your llfe ls ln your hands. Whlle we may noL be able Lo change Lhe ouLslde, we
can always change Lhe worklngs of our mlnds.

MosL poslLlve people glve generously, and Csler was no excepLlon. 1hroughouL hls
llfe he gave oLhers whaL he had-be lL a coaL Lo a man shlverlng ln Lhe cold, LuLelage
Lo a sLudenL, or care for a paLlenL. 1here are many sLorles of how he befrlended and
was of help Lo oLhers.

Cne day, Csler, on hls way Lo an Cxford graduaLlon and dressed ln academlc gown,
was asked Lo see a small boy wlLh severe whooplng cough compllcaLed by
bronchlLls. 1he chlld would noL eaL. 1he nurses and hls parenLs Lrled Lo feed hlm
wlLhouL success. Csler dld noL have much Llme buL acLed as Lhough he had plenLy.
Pe examlned Lhe chlld brlefly, and Lhen saL down aL Lhe bedslde. Pe carefully peeled
a peach, coaLed lL wlLh sugar, cuL lL lnLo small pleces, and offered Lhem Lo Lhe chlld
one aL a Llme, Lelllng Lhe boy LhaL lL was speclal frulL. Purrylng off Lo Lhe ceremony,
he gave Lhe boy's faLher a bleak prognosls buL conLlnued Lo vlslL Lhe chlld dally for
Lhe nexL 40 days. 8ecause Lhe boy had seen hlm as a maglcal flgure ln hls academlc
regalla, Csler broughL hls robe and puL lL on ouLslde Lhe room before each vlslL. 1he
chlld began Lo lmprove a few days afLer Lhe flrsL vlslL and made a full recovery.

ls Lell me LhaL my sLudenLs and Lhe docLors around me wlll slmllarly acL ln such a
compasslonaLe manner. 8emember Lhe Lmperor's 3 CuesLlons!

When ls Lhe MosL lmporLanL 1lML? Answer: nCW
Who ls Lhe MosL lmporLanL erson? Answer: 1he L8SCn you are wlLh now
WhaL ls Lhe MosL lmporLanL Lhlng Lo do? Answer: 1o do your besL aL Lhls momenL
for Lhe erson ln fronL of you

1he SecreL of success of a good docLor ls noL [usL knowledge and cllnlcal acumen,
Lhe very Lop secreL ls Slmply Lhls: 1C CA8L!


uear ?ln Llng, 18
Lh
March 2014


?our exam may be a few weeks away buL Csler asked Lo remlnd you LhaL Lhe exam ls
buL only a sollLary mllesLone ln a long road. Llfelong learnlng was as lmporLanL Lo
Csler as was llfelong Leachlng. ln Leachlng we become beLLer. ln Leachlng we learn
more Lhan we glve.

Csler, llke PlppocraLes, sLrongly advocaLed Lhe necesslLy Lo consLanLly sharpen your
sklll of observaLlon, an essenLlal componenL Lo becomlng a compeLenL physlclan.
LCCk and LCCk agaln, whaL do you see? Lven a novlce wlll see LhaL Lhe paLlenL has
goL one ear mlsslng buL Lhe good cllnlclan sees Lhe subLle varlaLlons from normal
LhaL lndlcaLes a devlaLlon from Lhe healLhy Lo Lhe dlseased sLaLe. All SLudenLs musL
use all of Lhelr senses and Lhe greaLesL sense Lo develop ls C8SL8vA1lCn. WL
observe whlle Lhe paLlenL walk ln, whlle he Lalks, whlle he undresses, and whlle he
cllmbs on Lhe couch.

And Lhe hlsLory ls so lmporLanL, LhaL Lo Csler we musL very carefully LlsLen Lo Lhe
paLlenL, he ls Lelllng you Lhe dlagnosls."



uear ?ln Llng, 19
Lh
March 2014

WL can Lalk abouL belng a good carlng docLor Llll Lhe cows come home buL lL wlll
mean noLhlng. 1he 1ruLh ls noL ln words buL ln acLs! lalLh, Lalk, speeches wlLhouL
works ls uead.

?our M8C exams are 1ough and for good reason for Lhe physlclan's flrsL duLy ls Lo
be compeLenL aL whaL he or she professes Lo be able Lo do, and Lo do lL conslsLenLly
and well. 1haL mlnlmal body of core knowledge ls essenLlal for anyone who clalms Lo
dlagnose and heal. 8lunLly puL, acLs of benevolenL compeLence ls compasslon, whlle
compasslon wlLhouL compeLence ls fraud.

We know of docLors who are klnd, pollLe, warm, and carlng-yeL Lhelr acLlons or
cllnlcal [udgmenL may be wrong. 1reaLmenL here ls Lhe placebo effecL. And Lhere are
dlagnosLlc supermen/women who pracLlce sLaLe-of-Lhe-arL evldence-based
medlclne, buL have such poor lnLeracLlons wlLh Lhe paLlenLs, colleagues and sLaff
LhaL ulLlmaLely all ls buL wasLed efforLs, and deparLmenLal envlronmenL, peer
relaLlonshlp and paLlenL care saboLaged for a slmple lack of baslc courLesy and
manners essenLlal for relaLlonshlps.

Clearly belng dedlcaLed Lo llfelong learnlng, belng observanL, developlng meLhods,
and belng Lhorough ls essenLlal for every healer. ln addlLlon, healers musL be
mlndful LhaL Lhey are Laklng care of a person and noL a dlsease, LhaL Lhey are leadlng
a Leam of colleagues from Lhe speclallsL Lo Lhe Pouseofflcer Lo Lhe medlcal sLudenL.
WhaL lmpresslon are we glvlng Lhem? WhaL llfe lessons are we Leachlng Lhem? Cne
of Csler's key recommendaLlons was, never leave Lhe bedslde wlLhouL a word of
encouragemenL." And Lhls applles Lo ALL, Lhe paLlenL and Lhe whole Leam.

1eachers cum cllnlclans are role models, we hope Lo be an embodlmenL of Lhe
humanlsLlc physlclan lmprlnLlng ln our charges mlnds Lhe quallLles we deem cruclal
Lo success as a compeLenL compasslonaLe docLor. Csler wroLe, 1he good physlclan
LreaLs Lhe dlsease, Lhe greaL physlclan LreaLs Lhe paLlenL who has Lhe dlsease."


I|na| Words
uear ?ln Llng, 20
Lh
March 2014

1oday ls 20Lh march. ln 20 days you wlll slL Lhrough 3 papers of 3 hours duraLlon, 9
hours of mlnd squeezlng Lo geL LhaL very lasL drop of medlcal wlsdom ouL of you.

27 years ago, l saL ln Lhe lecLure LheaLre aL Lhe 8oyal College of hyslclans and
Surgeons of Clasgow Lo pass Lhrough a slmllar exam. 1here were no compuLers Lhen
buL slldes pro[ecLed on Lhe screen and real papers Lo wrlLe on.

l plan Lo sLop Lhe uear ?ln Llng serles Loday. ?ou need Lo '8l Cuan' for Lhe nexL 20
days, Lo calm Lhe mlnd down. ?our accommodaLlon ln Spore has been arranged and
8ro !erry and hls famlly wlll love you llke Lhelr chlld.

l slgn off now, 4000 plus members of Lhls dlglLal classroom wlsh you well.

MeLLa,

rof