1

nuL Audlo flle 1: Cellular ln[ury 1

CnA1Lk 1: CLLLULAk kLAC1ICN 1C INIUk

key lssues hypoxla, cyanlde polsonlng, free radlcals, apopLosls, growLh alLernaLlons (l.e.


I. nypox|a = lnadequaLe oxygenaLlon of Llssue (same deflnlLlon of as shock). need C
2
for
oxldaLlon phosphorylaLlon paLhway where you geL A1 from lnner MlLo membrane (elecLron
LransporL sysLem, called oxldaLlve phosphorylaLlon). 1he lasL rxn ls C
2
Lo recelve Lhe elecLrons.
roLons are belng klcked off, go back lnLo Lhe membrane, and form A1, and A1 ln formed ln
Lhe mlLochondrla

A. 1erms:
1. Cxygen content = Pb x C
2
saLn + parLlal pressure of arLerlal oxygen
(Lhese are Lhe 3 maln Lhlngs LhaL carry C
2
ln our blood)

ln Pb, Lhe C
2
aLLaches Lo heme group (C
2

arLlal pressure of arLerlal C
2
ls C
2
dlssolved ln plasma

ln 88C, four heme groups (le musL be +2, lf le+ ls +3, lL cannoL carry C
2
)
1herefore, when all four heme groups have an C
2
on lL, Lhe C
2


2. C
2
S ls Lhe C
2
ln Lhe 88C ls aLLached 1C Lhe heme group = (measured by a pulse
oxlmeLer)

3. art|a| pressure of C
2
ls C
2
dlssolved ln LASMA

C
2
flow: from alveoll Lhrough Lhe lnLerphase, Lhen dlssolves ln plasma, and lncreases Lhe
parLlal pressure of C
2
, dlffuses Lhrough Lhe 88C membrane and aLLaches Lo Lhe heme
groups on Lhe 88C on Lhe Pb, whlch ls Lhe C
2


1herefore lf parLlal pressure of C
2
ls decreased, C
2
PAS 8 C
2

came from amounL LhaL was dlssolved ln plasma)

8. Causes of t|ssue hypox|a:

1. Ischem|a A81L8lAL nC1

2

MCC lschemla ls Lhrombus ln muscular arLery (b/c Lhls ls Lhe mcc deaLh ln uSA = Ml,
Lherefore Ml ls good example of lschemla b/c Lhrombus ls blocklng arLerlal blood flow,
produclng Llssue hypoxla)

CLher causes of Llssue lschemla: decrease ln Cardlac CuLpuL (leads Lo hypovolemla and
cardlogenlc shock) b/c Lhere ls a decrease ln arLerlal blood flow.
2. 2
nd
MCC of t|ssue hypox|a = hypoxem|a
nypox|a
nypoxem|a = cause of hypoxla (Lhey are noL Lhe same), deals wlLh Lhe parLlal pressure
of arLerlal C
2
(C
2
dlssolved ln arLerlal plasma, Lherefore, when Lhe parLlcle pressure of
C
2
ls decreased, Lhls ls called hypoxemla).

Pere are 4 causes of hypoxemla:
a. kesp ac|dos|s (ln Lerms of hypoxemla) u
parLlal pressure of gas musL = 760 aL aLmospherlc pressure (have C
2
, CC
2
, and
nlLrogen, nlLrogen remalns consLanL Lherefore, when you reLaln CC
2
, Lhls ls resp
acldosls, when CC
2
goes up, pC
2
PAS Lo go down b/c musL have Lo equal 760,
1herefore, every Llme you have resp acldosls, from An? cause, you have hypoxemla
b/c low arLerlal pC
2
, lncrease CC
2
= decrease pC
2
, and vlce versa ln resp alkalosls).

b. Vent||at|on defects besL example ls resp dlsLress syndrome (aka hyallne
membrane dz ln chlldren). ln adulLs, Lhls ls called AdulL 8uS, and has a venLllaLlon
defecL. LosL venLllaLlon Lo Lhe alveoll, buL sLlll have perfuslon, Lherefore have
creaLed an lnLrapulmonary shunL. Lxam quesLlon: pL wlLh hypoxemla, glven 100 of
C
2
for 20 mlnuLes, and pC
2
dld noL lncrease, Lherefore lndlcaLes a SPun1, masslve
venLllaLlon defecL.

c. erfus|on defects knock off blood flow
MCC perfuslon defecL = pulmonary embolus, especlally ln prolonged fllghLs, wlLh
slLLlng down and noL geLLlng up. SLasls ln velns of Lhe deep velns, leads Lo
propagaLlon of a cloL and 3-3 days laLer an embolus develops and embollzes. ln Lhls
case, you have venLllaLlon, buL no perfuslon, Lherefore Lhere ls an lncrease ln dead
space. lf you glve 100 C
2
for a perfuslon defecL, pC
2
wlll go u (way Lo dlsLlngulsh
venL from perfuslon defecL), b/c noL every slngle vessel ln Lhe lung ls noL perfused.

1herefore, perfuslon defecLs because an lncrease ln dead space, whlle venLllaLlon
defecLs cause lnLrapulmonary shunLs. 1o Lell Lhe dlfference, glve 100 C
2
and see
wheLher Lhe pC
2
sLays Lhe same, le does noL go up (shunL) or lncreases (lncrease ln
dead space).

3

d. D|ffus|on defect someLhlng ln Lhe lnLerphase LhaL C
2

flbrosls. 8esL exampleSarcoldosls (a resLrlcLlve lung dlsease), C
2
already have
Lrouble geLLlng Lhrough Lhe membrane, wlLh flbrosls lL ls worse. AnoLher example
ulmonary edema, C
2
cannoL cross, Lherefore Lhere ls a dlffuslon defecL. AnoLher
example ls plaln old fluld from hearL fallure leads Lo dyspnea, b/c acLlvaLed Lhe !
Cn Cn
Lake a full breaLh) b/c fluld ln lnLersLlum of Lhe lung, and Lhe ! recepLor ls lrrlLaLed.
1hese are Lhe four Lhlngs LhaL cause hypoxemla (resp acldosls, venLllaLlon defecLs,
perfuslon defecLs, and dlffuslon defecLs).

3. nemog|ob|n re|ated hypox|a
ln Lhe case of anemla, Lhe classlc mlsconcepLlon ls a hypoxemla (decrease ln pC
2
).
1here ls nC hypoxemla ln anemla, Lhere ls normal gas exchange (normal resplraLlon),
Lherefore normal pC
2
and C
2
saLuraLlon, buL Lhere ls a decrease ln Pb. 1haL ls whaL
anemla ls: decrease ln Pb. lf you have 3 gm of Pb, Lhere ls noL a whole loL of C
2
LhaL
geLs Lo Llssue, Lherefore geL Llssue hypoxla and Lhe paLlenL has exerLlonal dyspnea
wlLh anemla, exerclse lnLolerance.

a. Carbon monox|de (CC): classlc heaLer ln wlnLer, ln a closed space wlLh a heaLer
(heaLer have many combusLable maLerlals, auLomoblle exhausL and house flre. ln
Lhe house flre scenarlo, Lwo Lhlngs cause Llssue hypoxla: 1) CC polsonlng and 2)
Cyanlde polsonlng b/c upholsLery ls made of polyureLhrane producLs. When Lheres
heaL, cyanlde gas ls glven off, Lherefore pLs from house flres commonly have CC and
cyanlde polsonlng.

CC ls very dlffuslble and has a hlgh afflnlLy for Pb, Lherefore Lhe C
2
SA1n
decreased b/c lLs slLLlng on Lhe heme group, lnsLead of C
2
(remember LhaL CC has a
200x afflnlLy for Pb).

(Pb ls normal lLs nC1 anemla, pC
2
(C
2
dlssolved ln plasma) ls normal, Loo), when C
2

dlffuses lnLo Lhe 88C, CC already slLLlng Lhere, and CC has a hlgher afflnlLy for heme.
1o LreaL, glve 100 C
2
. uecrease of C
2

noL seen ln CC polsonlng b/c cherry red plgmenL MASkS lL, Lherefore makes Lhe
dlagnosls hard Lo make. MC sympLom of CC polsonlng = headache

b. Methemog|ob|n:
MeLhemoglobln ls le3+ on heme group, Lherefore C
2
CAnnC1 blnd. 1herefore, ln
meLhemoglobln polsonlng, Lhe only Lhlng screwed up ls C
2
saLuraLlon (b/c Lhe lron ls
+3, lnsLead of +2). Lxample: pL LhaL has drawn blood, whlch ls chocolaLe colored b/c
Lhere ls no C
2
on heme groups (normal pC
2
, Pb concenLraLlon ls normal, buL Lhe C
2

4

88C
a meLhemoglobln reducLase sysLem ln glycolyLlc cycle (reducLlon can reduce +3 Lo
+2).

Lxample: L from rocky mounLalns was cyanoLlc, Lhey gave hlm 100 C
2
, and he was
sLlll cyanoLlc (was drlnklng waLer ln mLns waLer has nlLrlLes and nlLraLes, whlch are
oxldlzlng agenLs LhaL oxldlze Pb so Lhe lron become +3 lnsLead of +2). Clue was LhaL
C
2
dld noL correcL Lhe cyanosls. 8x: lv meLhallne blue (uCC), anclllary 8x = vlLamln C
(a reduclng agenL). MosL recenL drug, uapsone (used Lo 8x leprosy) ls a sulfa and
nlLryl drug. 1herefore does Lwo Lhlngs: 1) produce meLhemoglobln and 2) have
poLenLlal ln produclng hemolyLlc anemla ln glucose 6 phosphaLe dehydrogenase
deflclencles. 1herefore, hemolysls ln C6u def ls referrlng Lo oxldlzlng agenLs,
causlng an lncrease ln peroxlde, whlch desLroys Lhe 88C, Lhe same drugs LhaL
produce hemolysls ln C6u def are sulfa and nlLryl drugs. 1hese drugs also produce
meLhemoglobln. 1herefore, exposure Lo dapsone, prlmaqulne, and 1M-SMx, or
nlLryl drugs (nlLroglycerln/nlLroprusslde), Lhere can be a combo of hemolyLlc anemla,
C6u def, and meLhemogloblnemla b/c Lhey are oxldlzlng agenLs. Common Lo see
meLhemogloblnemla ln Plv b/c pL ls on 1M-SMx for 8x of C. 1herefore, poLenLlal
compllcaLlon of LhaL Lherapy ls meLhemogloblnemla.

c. Curves: |eft and r|ght sh|fts
WanL a rlghL shlfLed curve wanL Pb wlLh a decreased afflnlLy for C
2
, so lL can
release C
2
Lo Llssues. Causes: 2,3 blsphosphoglyceraLe (8C), fever, low pP
(acldosls), hlgh alLlLude (have a resp alkalosls, Lherefore have Lo hypervenLllaLe b/c
you wlll decrease Lhe CC
2
, leadlng Lo an lncrease ln pC
2
, leadlng Lo a rlghL shlfL b/c
Lhere ls an lncrease ln synLhesls of 2,3 8C).

LefL shlfL CC, meLhemoglobln, Pbl (feLal Pb), decrease ln 2,3-8C, alkalosls
1herefore, wlLh CC, Lhere ls a decrease ln C
2


4. rob|ems re|ated to prob|ems re|ated to ox|dat|ve pathway

a. Most |mp: cytochrome ox|dase (lasL enzyme before lL Lransfers Lhe elecLrons Lo
C
2.
8emember Lhe 3 C cyLochrome oxldase, cyanlde, CC all lnhlblL cyLochrome
oxldase. 1herefore 3 Lhlngs for CC (1) decrease ln C
2
saL (hypoxla), (2) lefL shlfLs

blocks cyLochrome oxldase, so Lhe enLlre sysLem shuLs down

b. Uncoup||ng ablllLy for lnner mlLo membrane Lo synLheslze A1. lnner mlLo
membrane ls permeable Lo proLons. ?ou only wanL proLons Lo go Lhrough a cerLaln
5

pore, where A1 synLhase ls Lhe base, leadlng Lo producLlon of A1, y
random lnflux of proLons and LhaL ls whaL uncoupllng agenLs do. Lxamples:
dlnlLrylphenol (chemlcal for preservlng wood), alcohol, sallcylaLes. uncoupllng
agenLs causes proLons Lo go rlghL Lhrough Lhe membrane, Lherefore you are dralnlng
all Lhe proLons, and very llLLle A1 belng made. 8/c our body ls ln LoLal equlllbrlum
wlLh each oLher, rxns LhaL produce proLons lncrease (rxns LhaL make nAuP and
lAuP, Lhese were Lhe proLons LhaL were dellvered Lo Lhe elecLron LransporL sysLem).
1herefore any rxn LhaL makes nAuP and lAuP LhaL leads Lo proLon producLlon wlll
rev up rxns maklng nAuP and lAuP Lo make more proLons. WlLh lncreased raLe of
rxns, leads Lo an lncrease ln LemperaLure, Lherefore, wlll also see P?L81PL8MlA.
CompllcaLlon of sallcylaLe Loxlc = hyperLhermla (b/c lL ls an uncoupllng agenL).
AnoLher example: alcohollc on hoL day wlll lead Lo heaL sLroke b/c already have
uncoupllng of oxldaLlve phosphorylaLlon (b/c mlLo are already messed up).

1hese are all Lhe causes of Llssue hypoxla (lschemla, Pb relaLed, cyLo oxldase block,
uncoupllng agenLs). AbsoluLe key Lhlngs!

S. What happens when there |s:
a. resp acldosls Pb sLays same, C
2
C
2
decreased
(C
2
saL decreased b/c pC
2
ls decreased)
b. anemla only Pb ls affecLed (normal C
2
C
2
)
c. CC/meLhemoglobln Pb normal, C
2
C
2
normal
8x CC 100 C
2
, meLhemo lv meLhallne blue (uCC) or vlL C (ascorblc acld)

C. Decreased of A1 (as a resu|t of t|ssue hypox|a)

1. Most |mp: have to go |nto anaerob|c g|yco|ys|s, end producL ls lacLlc acld (pyruvaLe ls
converLed Lo lacLaLe b/c of lncreased nAuP), need Lo make nAu, so LhaL Lhe nAu can
feedback lnLo Lhe glycolyLlc cycle Lo make 2 more A1. Why do we have Lo use
anaeroblc glycolysls wlLh Llssue hypoxla? MlLochondrla are Lhe one LhaL makes A1,
however, wlLh anaeroblc glycolysls, you make 2 A1 wlLhouL golng lnLo Lhe
L 88C
anaeroblc glycolysls, Lherefore survlvlng on 2 A1 per glucose lf you have Llssue hypoxla.
MlLochondrlal sysLem ls LoLally shuL down (no C
2
aL Lhe end of Lhe elecLron LransporL
sysLem can only geL 2 A1 wlLh anaeroblc glycolysls).

Cood news geL 2 A1
8ad news bulld up of lacLlc acld ln Lhe cell and ouLslde Lhe cell (lncreased anlon-gap
meLabollc acldosls wlLh Llssue hypoxla) due Lo lacLlc acldosls from anaeroblc glycolysls.

6

Powever, causes havoc lnslde Lhe cell b/c lncrease of acld wlLhln a cell wlll denaLure
proLelns (wlLh sLrucLural proLelns messed up, Lhe conflguraLlon wlll be alLered), enzymes
wlll be denaLured, Loo. As a resulL, cells cannoL auLodlgesL anymore b/c enzymes are
desLroyed b/c bulldup of acld. 1lssue hypoxla wlll Lherefore lead Lo CCACuLA1lCn
necrosls (aka lnfarcLlon). 1herefore, bulldup of lacLlc acld wlLhln Lhe cell wlll lead Lo
CoagulaLlon necrosls.

2. 2
nd
prob|em of |ack|ng A1: a|| A1 pumps are screwed up b/c Lhey run on A1. A1
ls Lhe power, used by muscles, Lhe pump, anyLhlng LhaL needs energy needs A1. Na]k
pump blocked by dlglLalls Lo allow na Lo go lnLo cardlac muscle, so Ca channels open
Lo lncrease force of conLracLlon (Lherefore, someLlmes you wanL Lhe pump blocked),
and someLlmes you wanL Lo enhance lL.

WlLh no A1, na lnLo Lhe cell and lL brlngs P20, whlch leads Lo cellular swelllng (whlch ls
reverslble). 1herefore, wlLh Llssue hypoxla Lhere wlll be swelllng of Lhe cell due Lo
decreased A1 (Lherefore wlll geL C
2
back, and wlll pump lL ouL Lherefore lL ls
8LvL8SA8LL).

ln Lrue 88C, anaeroblc glycolysls ls Lhe maln energy source b/c Lhey do noL have
lA 1CA

3. Ce|| w|thout C
2
|eads to |rrevers|b|e changes.

Ca changes w|th |rrevers|b|e damage Ca/A1ase pump. WlLh decrease ln A1, Ca has
easy access lnLo Lhe cell. WlLhln Lhe cell, lL acLlvaLes many enzymes (le phosphollpases
ln Lhe cell membranes, enzymes ln Lhe nucleus, leadlng Lo nuclear pyknosls (so Lhe
chromaLln dlsappears), lnLo goes lnLo Lhe mlLo and desLroys lL).

Ca acLlvaLes enzymes, hypercalcemla leads Lo acuLe pancreaLlLls b/c enzymes ln Lhe
pancreas have been acLlvaLed. 1herefore, wlLh lrreverslble changes, Ca has a ma[or role.
Cf Lhe Lwo LhaL geL damaged (mlLo and cell membrane), cell membrane ls damaged a loL
worse, resulLlng ln bad Lhlngs from Lhe ouLslde Lo geL lnLo Lhe cell. Powever, Lo add
lnsulL Lo ln[ury, knock off mlLochondrla (energy produclng facLory), lL ls a very bad
Ck-M8 for Ml, Lransamlnases for hepaLlLls (SCC1 and AS1/AL1),
amylase ln pancreaLlLls.

II. Iree kad|ca|s
Llver wlLh brownlsh plgmenL llpofuscln (seen on gross plc, can also be hemoslderln,
blllrubln, eLc, Lherefore need Lo have a case wlLh Lhe gross plc), end producLs of free radlcal
damage are llpofuscln b/c cerLaln Lhlngs are noL dlgesLlble (lnclude llplds).
7


A. Def|n|t|on of free rad|ca| compound wlLh unpalred elecLron LhaL ls ouL of orblL,


8. 1ypes of Iree kad|ca|s:
1. Cxygen: We are breaLhlng C
2
, and C
2
can glve free radlcals. lf glve a person 30 C
2
for a perlod of Llme, wlll geL superoxlde free radlcals, whlch lead Lo reperfuslon ln[ury,
esp afLer glvlng LA when Lrylng Lo rld a damaged Lhrombus. CxygenLaLed blood goes
back lnLo Lhe damaged cardlac muscle=reperfuslon ln[ury. klds wlLh resp dlsLress
syndrome can geL free radlcal ln[ury and go bllnd b/c Lhey desLroy Lhe reLlna called
reLlnopaLhy premaLurlLy, also leads Lo bronchopulmonary dysplasla, whlch leads Lo
damage ln Lhe lungs and a crlppllng lung dlsease.

2. WaLer ln Llssues converLed Lo hydroxyl free radlcals, leadlng Lo muLaLlons ln Llssues.
CompllcaLlon of radlaLlon Lherapy ls CAnCL8 (MC cancer from radlaLlon ls leukemla, due
Lo hydroxyl free radlcals). le2+ produces hydroxyl free radlcals b/c of Lhe fenLon rxn.
1hls ls whaL makes le overload dlseases so dangerous, b/c wherever le ls overloaded,
leads Lo hydroxyl free radlcals whlch wlll damage LhaL Llssue (Lherefore, ln llver leads Lo
clrrhosls, ln hearL leads Lo resLrlcLlve cardlomyopaLhy, ln pancreas leads Lo fallure, and
malabsorpLlon, along wlLh dlabeLes).
Audlo flle 2: Cell ln[ury 2
3. 1ylenol (aka aceLamlnophen):
MCC drug lnduced fulmlnanL hepaLlLls b/c free radlcals (esp LargeLs Lhe llver, buL also
LargeLs Lhe kldneys). CyLochrome 430 ln llver meLabollzes drugs, and can change drugs
lnLo free radlcals. urugs are ofLen changed ln Lhe llver Lo Lhe acLlve meLabollLe le
phenyLoln. Where ln Lhe llver does aceLamlnophen LoxlclLy manlfesL lLself? rlghL
around cenLral veln. 1reaLmenL: n-aceLylcysLelne, how? Well, Lhe free radlcals can be
neuLrallzed. Superoxlde free radlcals can be neuLrallzed wlLh supraoxlde dlsmuLase
(SCu). CluLaLhlone ls Lhe end producL of Lhe hexose/penLose phosphaLe shunL and Lhls
shunL also generaLes nAuP. Maln funcLlon ls Lo neuLrallze free radlcals (esp drug free
radlcals, and free radlcals derlved from peroxlde). CluLaLhlone geLs used up ln
neuLrallzlng Lhe aceLamlnophen free radlcals. 1herefore, when glve n-aceLylcysLelne
(aka mucamlsL), you are replenlshlng gluLaLhlone, Lherefore glvlng subsLraLe Lo make
more gluLaLhlone, so you can keep up wlLh neuLrallzlng aceLamlnophen free radlcals.
(llke meLhoLrexaLe, and leukoverln rescue uslng up Loo much folaLe, leukoverln
supplles Lhe subsLraLe Lo make unA, folaLe reducLase).

4. Carbon LeLrachlorlde: CCl4 can be converLed Lo a free radlcal ln Lhe llver (CCl3) ln Lhe
llver, and a free radlcal can be formed ouL of LhaL (seen ln dry cleanlng lndusLry).

8

3. Asplrln + 1ylenol = very bad for kldney (Lakes a long Llme for damage Lo be seen).
lree radlcals from aceLamlnophen are desLroylng Lhe renal medulla *only recelves 10
of Lhe blood supply-relaLlvely hypoxlc) and renal Lubules. Asplrln ls knocklng off Lhe
vasodllaLor CL2, whlch ls made ln Lhe afferenL arLerlole. 1herefore AC ll (a
vasoconsLrlcLor) ls lefL ln charge of renal blood flow aL Lhe efferenL arLerlole. LlLher
sloughlng of medulla or desLroyed ablllLy Lo concenLraLe/dlluLe your urlne, whlch ls
called analgeslc nephropaLhy (due malnly Lo aceLamlnophen).

III. Apoptos|s

rogrammed cell deaLh. ApopLoLlc genes n
funcLlons: (1) embryo small bowel goL lumens from apopLosls. (2) klng of Lhe body ?
for men), Mll very lmp b/c all mullarlan sLrucLures (uLerus, cervlx, upper 1/3 of
vaglna) are gone, Lherefore, no mullarlan sLrucLures. Mll ls a slgnal worklng wlLh
apopLosls, vla caspasases. 1hey desLroy everyLhlng, Lhen wrap everyLhlng ln apopLoLlc
bodles Lo be desLroyed, and llpofuscln ls lefL over. (3)lor woman x
A
go Lhe ovarlan rouLe, Lherefore apopLosls knocked off Lhe wolflan sLrucLures (epldydymls,
semlnal veslcles, and vas deferens). (4) 1hymus ln anLerlor medlasLlnum large ln klds, lf
absenL, lL ls ulCeorge syndrome (absenL Lhymlc shadow), and would also have LeLany,
cause of Lhymus Lo lnvoluLe ls apopLosls. (3) ApopLosls ls Lhe ma[or cancer kllllng
mechanlsm. (6) rocess of aLrophy and reduced cell or Llssue mass ls due Lo apopLosls. Lx.
PepaLlLls councllman body (looks llke eoslnophlllc cell wlLhouL apopLosls) of apopLosls
(lndlvldual cell deaLh wlLh lnflammaLlon around lL). !usL needs a slgnal (hormone or
chemlcal) whlch acLlvaLe Lhe caspases, and no lnflammaLlon ls around lL. ApopLosls of
neurons loss braln mass and braln aLrophy, and leads Lo lschemla. 8ed cyLoplasm, and
pynoLlc nucleas. ALheroscleroLlc plaque. 1herefore, apopLosls ls lnvolved ln embryo,
paLhology, and knocklng off cancer cells.

IV. 1ypes of necros|s manlfesLaLlons of Llssue damage.

A. Coagu|at|on Necros|s: 8esulLs ofLen from a sudden cuLoff of blood supply Lo an organ l.e.
lschemla (deflnlLlon of lschemla = decrease ln arLerlal blood flow). ln lschemla, Lhere ls no
oxygen Lherefore lacLlc acld bullds up, and leads Lo coagulaLlon necrosls. Cross
manlfesLaLlon of coagulaLlon necrosls ls lnfarcLlon. under mlcroscope, looks llke cardlac
muscle buL Lhere are no sLrlaLlons, no nuclel, brlghL red, no lnflammaLory lnfllLraLe, all due
Lo lacLlc acld LhaL has denaLured and desLroyed all Lhe enzymes (cannoL be broken down
neuLrophlls need Lo come ln from Lhe ouLslde Lo breakdown). 1herefore, vague ouLllnes =
coagulaLlon necrosls (see color change ln hearL).

9

1. ale vs hemorrhaglc lnfarcLlons: look aL conslsLency of Llssue.

(a) Cood conslsLency = grossly look pale: lnfarcL: hearL, kldney, spleen, llver (raresL of
Lhe organ Lo lnfarcL b/c dual blood supply), le coagulaLlon necrosls. Lxample of a pale
lnfarcLlon of Lhe spleen, mosL llkely due Lo emboll from lefL slde of hearL, causes of
emboll: vegeLaLlons (rarely embollze ln acuLe rheumaLlc endocardlLls), lnfecLlve
endocardlLls, mlLral sLenosls (hearL ls repeaLedly aLLacked by group A beLa hemolyLlc
sLrepLococcus), and cloLs/Lhrombl. 1he worsL arrhyLhmla assoclaLed wlLh embollzaLlon
ln Lhe sysLemlc clrculaLlon ls aLrlal flb b/c Lhere ls sLasls ln Lhe aLrla, cloL formaLlon, Lhen
lL vlbraLes (lll pleces of cloL embollze).

Gangrenous Necros|s: dry and wet gangrene: lcLure of a dry gangrene noL weL
C
and posslble Lhrombosls, (dry gangrene relaLed Lo coagulaLlon necrosls relaLed wlLh
lschemla (deflnlLlon of lschemla = decrease ln arLerlal blood flow), whlch ls due Lo
aLherosclerosls of Lhe popllLeal arLery. aLhogenesls of Ml: coronary Lhrombosls
overlylng Lhe aLheromaLous plaque, leadlng Lo lschemla, and lumen ls blocked due Lo
Lhrombosls. MCC nonLraumaLlc ampuLaLlon = dlabeLes b/c enhanced aLherosclerosls
(popllLeal arLery = dangerous arLery). Coronary ls also dangerous b/c small lumen. ln
weL gangrene
necrosls.
(b) Loose conslsLency of Llssue= hemorrhaglc lnfarcL: bowel, LesLes (Lorslon of Lhe
LesLes), especlally Lhe lungs b/c ls has a loose conslsLency and when Lhe blood vessels
88C

Lxample: hemorrhaglc lnfarcLlon of small bowel due Lo lndlrecL hernla. 2
nd
MCC of
bowel lnfarcLlon ls geLLlng a plece of small bowel Lrapped ln lndlrecL hernlal sac. MCC of
bowel lnfarcLlon ls adheslons from prevlous surgery.

Lxample: ln Lhe Lung hemorrhaglc lnfarcLlon, wedge shaped, wenL Lo pleural surface,
Lherefore have effuslon and exudaLes, neuLrophlls ln lL, have pleurlLlc chesL paln (knlfe-
llke paln on lnsplraLlon). ulmonary embolus leads Lo hemorrhaglc lnfarcLlon.

8. L|quefact|ve Necros|s:
LxcepLlon Lo rule of CoagulaLlon necrosls seen wlLh lnfarcLlons: braln.
MC slLe of lnfarcLlon from caroLld arLery why we llsLen for a brulL (hearlng for a nolse
LhaL ls golng Lhru a vessel LhaL has a narrow lumen place wlLh Lhrombus develops over
aLheroscleroLlc plaque and leads Lo sLroke), leads Lo LranslenL lschemlc aLLacks ls llLLle
aLheroscleroLlc plaques golng Lo llLLle vessels of Lhe braln, produclng moLor and sensory
8 ln braln, asLrocyLes ls
10

analogous Lo Lhe flbroblasLs b/c of proLoplasmlc processes. 1herefore, acLlng llke

Lhe braln. 1herefore, lnfarcLlon of Lhe braln baslcally llquefles lL (has no sLrucL), and you
see a cysL space ||quefact|ve necros|s. 1herefore, excepLlon Lo Lhe rule of lnfarcLlons
noL belng coagulaLlve necrosls ls Lhe braln and lL undergoes llquefacLlve necrosls (no
sLruc, Lherefore leaves a hole). Cerebral abscess and old aLheroscleroLlc sLroke -boLh
are llquefacLlve necrosls.

LlquefacLlve llquefles, Lhlnk neuLrophll, b/c Lhelr [ob ls Lo phagocyLosls wlLh Lhelr

lnvolved (usually acuLe lnfecLlon produclng an abscess or an lnflammaLory condlLlon,
whlch llquefles Llssue). 1herefore, llquefacLlve necrosls usually applles Lo acuLe
lnflammaLlon, relaLed Lo neuLrophlls damaglng Lhe Llssue. LxcepLlon Lo Lhe rule:
llquefacLlve necrosls relaLed Lo lnfarcL (noL an lnflammaLory condlLlon, lL [usL llquefles)
(sllde shows llquefacLlve necrosls due Lo lnfecLlon ln Lhe braln). So, lf you lnfarcL Lhe
braln, or have an lnfecLlon, or have an abscess lL ls Lhe same process llquefacLlve
necrosls.

Lxample: Abscess W C
whlch leads Lo abscesses wlLh sLaph aur. Coagulase converLs flbrlnogen lnLo flbrln, so lL
locallzes Lhe lnfecLlon, flbrln sLrands geL ouL, resulLlng ln an abscess. SLrep: releases
hya CAC
Llssue (cellullLls). lrom polnL of vlew of necrosls, neuLrophlls are lnvolved, Lherefore lL ls
llquefacLlve necrosls.
Lxample: A8SCLSS: Lung yellowlsh areas, hlgh fever and producLlve cough, gram sLaln
MCC
bronchopneumonla.). noL hemorrhaglc b/c lLs pale, and wedged shaped necrosls aL Lhe
perlphery, whlch leads Lo pleurlLlc chesL paln.

Lxample: pL wlLh fever, nlghL sweaLs, wL loss M Lb, whlch has granulomaLous (caseous)
necrosls. aLhogenesls of granuloma (lnvolves lL- 1
u).

C. Caseous (cheesy cons|stency) Necros|s: elLher have mycobacLerlal lnfecLlon (any
lnfecLlons, lncludlng aLyplcals, or sysLemlc fungal lnfecLlon), Lhese are Lhe CnL? Lhlngs LhaL
l
Lo cheesy appearance.

Sarcoldosls geL granulomas, buL Lhey are noL caseous b/c Lhey are noL mybacLerlum or

11

C geL granulomas, buL noL caseous b/c noL relaLed Lo mycobacLerlum or sysLemlc
fungl.

D. Iat Necros|s:

1. LnzymaLlc laL necrosls: unlque Lo pancreas
Lxample: pL wlLh eplgasLrlc dlsLress wlLh paln radlaLlng Lo Lhe back pancreaLlLls
(cannoL be epLlc ulcer uz b/c pancreas ls reLroperlLoneal), Lherefore [usL have
eplgasLrlc paln radlaLlng Lo Lhe back. A Lype of enzymaLlc lA1 necrosls (Lherefore
necrosls relaLed Lo enzymes). LnzymaLlc faL necrosls ls unlque Lo Lhe pancreas b/c
lA C
lA
saponlflcaLlon (soap/llke salL formaLlon)), Lhese can be seen on xrays b/c have calclum ln
Lhem. Lxample: A pL wlLh paln consLenLly peneLraLlng lnLo Lhe back, show x-ray of 8uC.
ux ls pancreaLlLls and esp seen ln alcohollcs. PlsLo sllde on enzymaLlc faL necrosls
blulsh dlscoloraLlon, whlch ls calclflcaLlon (a Lype of dysLrophlc calclflcaLlon-calclflcaLlon
of damaged Llssue). WhaL enzyme would be elevaLed? Amylase and llpase (llpase ls
more speclflc b/c amylase ls also ln Lhe paroLld gland, small bowel, and falloplan Lubes).
WhaL Lype of necrosls? AnoLher example: LnzymaLlc faL necrosls. underlylng cause?
Alcohol produces a Lhlck secreLlon LhaL wlll lead Lo acLlvaLlon of enzymes, whlch leads Lo
pancreaLlLls. 1herefore, whenever you see blue dlscoloraLlon and aLheroscleroLlc
plaque ln a pancreas, lL wlll be calclum.

2. 1raumaLlc laL necrosls: Lxample: woman wlLh damage Lo breasLs ls 18AuMA1lC lA1
necrosls (noL enzymaLlc), lL can calclfy, can look llke cancer on mammogram. ulff bLwn
LhaL and calclflcaLlon ln breasL cancer ls LhaL lL ls palnluL. (cancer = palnless). 1raumaLlc
faL Llssue usually occurs ln breasL Llssue or oLher adlpose Llssue

L. I|br|no|d necros|s: (Lhe -
1 necrosls of lmmunologlc dz:
Lxamples of lmmunologlc dz:
alpable purpura = small vessel vascullLls (lmmune complex Lype lll).
llbrlnold necrosls has lmmune complex deposlLlon of small vessel.
aLhogenesls of lmmune complex: damage of Lype lll P? (an lmmune complex ls an Ag-
Ab clrculaLlng ln Lhe clrculaLlon, lL deposlLs wherever clrculaLlon Lakes lL le glomerulus,
small vessel, wherever). lL acLlvaLes Lhe complemenL sysLem (Lhe alL sysLem), whlch
produces C3a, whlch ls chemoLacLlc Lo neuLrophlls. 1herefore, damage done as a resulL
of Lype lll P? ls done by neuLrophlls. And Lhey are Lhere b/c Lhe lmmune complex
acLlvaLed Lhe alLernaLlve complemenL sysLem. 1he complex has llLLle Lo do wlLh Lhe

12


Penoch-Scholeln purpura lll
P?). 8hemaLlc fever (vegeLaLlons off Lhe mlLral valve) have flbrln llke (flbrlnold
necrosls) maLerlals (necrosls of lmmunologlc dz). Mornlng sLlffness = rheumaLold
arLhrlLls, see flbrnold necrosls b/c lmmunologlc damage. 1herefore, flbrlnold necrosls ls

glomerulonephrlLls, and ln lupus glomerulonephrlLls lnvolvlng lmmune complexes).

I. L|ver: 1rlad area: porLal veln, hepaLlc arLery, blle ducL. Llver ls unlque b/c lL has dual
blood supply and so hepaLlc arLery and and porLal veln wlll dump blood lnLo slnusolds.
CLher examples of slnusold organs are 8M and spleen. CharacLerlsLlc of slnusolds: gaps
88C
and lnflammaLory cells). C8M ls fenesLraLed, have llLLle Llny pores wlLhln Lhe cells, for
fllLraLlon. Slnusolds have gaps so large cells can geL Lhrough Lhem (noL Lrue wlLh C8M b/c lL
ls lnLacL, and lll pores allow fllLraLlon). orLal veln blood and hepaLlc arLery blood go
Lhrough slnusolds, and evenLually Laken up by cenLral veln, whlch becomes Lhe hepaLlc
veln. 1he hepaLlc veln dumps lnLo Lhe lnf vena cava, whlch goes Lo Lhe rlghL slde of Lhe
hearL. 1herefore, Lhere ls a communlcaLlon beLween rlghL hearL and llver. 8lghL Pl (blood
fllls behlnd falled hearL), Lherefore Lhe llver becomes congesLed wlLh blood, leadlng Lo
nuLmeg llver (aka congesLlve hepaLomegaly). lf you block Lhe porLal veln, noLhlng happens
Lo Lhe llver, b/c lL ls 8LlC8L Lhe llver. 8lockage of hepaLlc veln leads Lo budd chlarl and
llver becomes congesLed. Whlch parL of llver ls mosL suscepLlble Lo ln[ury normally? Around
cenLral veln, b/c lL geLs flrsL dlbbles on C
2
comlng ouL of Lhe slnusolds (zone 1). Zone 2 ls
where yellow fever wlll hlL (mldzone necrosls) due Lo ldes egypLl. Zone 3, around porLal
veln, whlch wlll have leasL C
2
(analogous Lo renal medulla, whlch only recelves 10 of Lhe
blood supply, and Lhe corLex recelves 90). laLLy change ls around zone 3 (parL around
cenLral veln). 1herefore, when asklng abouL aceLamlnophen LoxlclLy, whlch parL ls mosL
suscepLlble? Around Lhe cenLral veln b/c lL geLs Lhe leasL amounL C
2
, and Lherefore cannoL
combaL free radlcal ln[ury.
1. Alcohol relaLed llver damage:
(a) MCC faLLy change: alcohol.
(b) MeLabollsm of alcohol: nAuP and aceLyl CoA (aceLaLe ls a lA, and aceLyl CoA can
lA nAuP lsm of alcohol,
Lherefore, for blochemlcal rxns: WhaL causes pyruvaLe Lo form lacLaLe ln anaeroblc
glycolysls? nAuP drove lL ln LhaL dlrecLlon, Lherefore always see lacLlc acldosls (a
nAuP ln LhaL
dlrecLlon. Also, ln fasLlng sLaLe, alcohollc wlll have Lrouble maklng glucose by
gluconeogenesls b/c need pyruvaLe Lo sLarL lL off. Powever, you have lacLaLe (and
noL pyruvaLe) Lherefore alcohollcs wlll have fasLlng hypoglycemla. AceLyl CoA can
also make keLone bodles (aceLoaceLyl CoA, PMC CoA, and beLa hydroxybuLyrlc acld).
13

S nAuP
1herefore, Lwo Lypes of meLabollc acldosls seen ln alcohollcs are lacLlc acldosls (b/c
drlvlng pyruvaLe lnLo lacLaLe) and lncreased synLhesls of keLone bodles b/c excess
aceLyl CoA, maln keLoacld = beLa hydroxybuLyrlc acld. Why does lL produce faLLy
change? ln glycolysls, around rxn 4, geL lnLermedlaLes dlhydroxyaceLone phoshphaLe
(nAuP rxn) and ls forced Lo become glycerol 3-phosphaLe. 8lg Llme board quesLlon!
WlLh glycerol 3 phosphaLe shuLLle, geL A1. Also lmp Lo carbohydraLe backbone for
lA 1C l
llver, Lhe llpld fracLlon lf vLuL (endogenous 1C ls synLheslzed ln Lhe llver from
glycerol 3 phosphaLe derlved from glycolysls). 8esLrlcLlng faL wlll nC1 decrease Lhe
synLhesls of vLuL. 8esLrlcLlng carbs WlLL decrease Lhe vLuL synLhesls b/c lL ls
glucose lnLermedlaLe lL ls made from. Clycerol 3 phosphaLe ls a producL of glycolysls
MC
Audlo flle 3: lnflammaLlon 1
2. kwashlorker kld wlLh faLLy change. 1he mechanlsm: when you make vLuL, and Lo
be able Lo geL lL ouL of Lhe llver, Lhe vLuL musL be surrounded by apoproLelns. ln
kwashlorkor, Lhere ls decreased proLeln lnLake, Lhey have adequaLe number of calorles,
buL lLs all carbs. 1herefore, Lhey cannoL geL vLuL LhaL Lhey made ln Lhe llver ouL b/c
Lhere are no apollpoproLelns Lo cover lL and puL lL ouL ln Lhe bloodsLream and solublllze
lL ln waLer. Llpld and waLer do noL mlx, Lherefore lL ls necessary Lo puL proLelns around
Lhe llpld Lo dlssolve lL ln waLer. 1herefore, Lhe proLuberanL abdomen ln Lhese pLs ls
Lhere for Lwo reasons: 1) decreased proLeln lnLake whlch decreases oncoLlc pressure,
leadlng Lo asclLes. 2) 1he blggesL reason ls LhaL Lhey have huge llvers relaLed Lo faLLy
change. 1he mechanlsm for faLLy change ls dlfferenL from alcohol b/c ln alcohol, Lhe
mech ls due Lo lncreased synLhesls of vLuL. ln Lhls case, Lhere ls a lack of proLeln Lo puL
around Lhe vLuL and exporL lL ouL of Lhe llver.

3. Pemoslderln and lerrLln: brlef dlscusslon: lerrlLln = soluble form of clrculaLlng le,
and ls a good marker l 8M l l
problem l A C u l
hemochromaLosls and hemoslderosls (would be elevaLed). lerrlLln ls a soluble form of
le, whlle hemoslderln ls an lnsoluble form of le sLorage, and ls sLored ln macrophages
and 8M. SLaln lL wlLh russlan blue.

V. 1ypes of ca|c|f|cat|on: dysLrophlc and meLasLaLlc

A. Dystroph|c ca|c|f|cat|on: means abnormal calclflcaLlon. 1he damaged Llssue geLs
calclfled.
1. Lxample: Seen ln enzymaLlc faL necrosls (chalky whlLe areas on x-ray are a resulL of
dysLrophlc calclflcaLlon).
14

2. Lxample: fooLball player wlLh hemaLoma ln fooL, LhaL becomes calclfled
dsysLrophlcally (Ca blnds and co-produces dysLrophlc Ca deposlLs). Serum Ca ls normal,
buL damaged Llssue becomes calclfled. Cccurs ln aLheromaLous plaques (causes serlous
Llssue damage), Lherefore Lhey are dlfflculL Lo dlssolve (need Lo be on Lhe ornlsh dleL a
vegan dleL).
3. MCC aorLlc sLenosls (MCC: congenlLal blcuspld aorLlc valve) = dysLrophlc calclflcaLlon
(also leads Lo a hemolyLlc anemla). Sllde: Lhe aorLa has only 2 valves dolng Lhe [ob of
Lhree, and geLs damaged, leadlng Lo dysLrophlc calclflcaLlon whlch narrows orlflce of
valve, leadlng Lo aorLlc sLenosls.

8. Metastat|c ca|c|f|cat|on: ln cases of Pypercalcemla or hyperphosphaLemla, Calclum ls
acLually made Lo deposlL ln normal Llssues, non-damaged Llssues.
MCC hypercalcemla (ouLslde of hosplLal) = prlmary hyperparaLhyroldlsm
MCC hypercalcemla (lnslde Lhe hosplLal) = mallgnancy lnduced hypercalcemla.
WlLh hypercalcemla, can puL Ca ln nC8MAL Llssues, Lhls ls called meLasLaLlc calclflcaLlon. ln
dysLrophlc calclflcaLlon Lhere ls damaged Llssue wlLh normal serum Ca levels. MeLasLaLlc
calclflcaLlon ls when Lhere ls hlgh Ca or phosphorus serum levels (acLually when Ca ls
deposlLed lnLo bone, lL ls Lhe phosphorus parL of solublllLy producL LhaL drlves Ca lnLo
bone). Plgh phosphaLe levels (very dangerous) wlll Lake Ca and drlve lL lnLo normal Llssue.
1hls ls why have Lo puL a pL wlLh renal fallure on dlalysls (have hlgh phosphorus serum
levels) Lherefore need Lo dlalyze Lhe phosphaLe b/c Lhe phosphaLe wlll drlve Ca lnLo normal
Llssue le hearL, conducLlon sysLem, renal Lubules, basemenL membrane (nephrocalclnosls)
all lead Lo damage.

VI. Ce|| Membrane Defects

A. k8C membrane defect: SpherocyLosls ls a defecL ln specLrln wlLhln 88C cell membrane,

Absence of specLrln wlLh ln Lhe 88C does noL allow Lhe 88C Lo form a blconcave dlsk, lL ls
defecLlve, and Lherefore forms a sphere.

8!""Ub|qu|t|n sLress proLeln. Plgh ublqulLln levels are assoclaLed wlLh hlgh levels of sLress.
Some of Lhe lnLermedlaLe fllamenLs (keraLln, desmln, vlmenLln) are parL of Lhe
W
lnLermedlaLe fllamenLs geL damaged, Lhe ublqulLln marks Lhen for desLrucLlon. 1he
lnLermedlaLe fllamenLs have been Lagged (ublqulnaLed) and marked for desLrucLlon. Some
of Lhese producLs have names, for example: Lhere are open spaces wlLhln Lhe llver Llsse,
Lhese spaces are faL and Lhey are probably due Lo alcohol. 1he ublqulnlLed producLs of Lhe
llver are called Mallory bodles. 1hese are Lhe resulL of ublqulnaLed fllamenLs called keraLln
and Lhese are seen ln alcohollc hepaLlLls. AnoLher example: Sllver sLaln of neuroflbllary
15

Langles !acob cruLzfelL and alzhelmers dz. 1au proLeln ls assoclaLed wlLh neuroflb Langles,
Lhls ls an example of a ublqulnaLed neurofllamenL. Lxample S
uz lnclude lncluslons called Lewy bodles, neuroLransmlLLer deflclency ls dopamlne. Lewy
bodles are ublqulnaLed neurofllamenLs. 1herefore, Mallory bodles, Lewy bodles, and
neuroflb Langles are all examples of ublqulnLaLlon.

VII. Ce|| Cyc|e- very very lmporLanL: blg blg blg Llme

A. D|fferent types of ce||s:
1. Lablle cells cell where Lhe dlvlslon ls vla a sLem cell. 1hree Llssues LhaL has sLem
cells: bone marrow, basemenL membrane of skln, and Lhe base of crypLs ln Lhe lnLesLlne.
1hese cells have Lhe Lendency of belng ln Lhe cell cycle a loL. ln pharm: Lhere are cell
cycle speclflc and cell cycle nonspeclflc drugs. 1he cells LhaL are mosL affecLed by Lhese
drugs are Lhe lablle cells b/c Lhey are ln Lhe cell cycle. CompllcaLlons of Lhese drugs are
8M suppresslon, dlarrhea, mucocldls, and rashes on Lhe skln (Lhere are sLem cells ln all
Lhese Llssues!).

2. SLable cells ln resLlng phase, C
o
phase. MosL of perenchymal organs (llver, spleen,
and kldney) and smooLh muscle are sLable cells. SLable cells can ungo dlvlslon, buL mosL
of Lhe Llme Lhey are resLlng, and someLhlng musL sLlmulaLe Lhem Lo geL lnLo Lhe cell
cycle and dlvlde le a hormone or a growLh facLor. lor example: esLrogen ln woman
wlll help ln Lhe prollferaLlve phase of Lhe mensLrual cycle. 1he endomeLrlal cells are
lnlLlally ln Lhe C
o
phase and Lhen Lhe esLrogen sLlmulaLed Lhe cells Lo go lnLo Lhe Lhe cell
cycle. 1herefore, Lhey can dlvlde, buL Lhey have Lo be lnvlLed by a hormone or a growLh
facLor.

3. ermanenL cells can no longer geL lnLo Lhe cell cycle, and have been permanenLly
dlfferenLlaLed. 1he oLher Lypes of muscle cells: sLrlaLed, cardlac and neuronal cells.
Cnly muscle LhaL ls nC1 a permanenL Llssue = smooLh muscle, hyperplasla = lncrease ln
#, whlle hyperLrophy = lncrease ln slze. Would a permanenL cell be able Lo under
hyperplasla? nC, b/c LhaL means more coples of lL. Can lL go under hyperLrophy? ?es. A
smooLh muscle cell can undergo hyperplasla Anu hyperLrophy.

8. D|fferent phases of ce|| cyc|e:
1. C
1
phase: 1he mosL varlable phase of cell cycle ls Lhe C
1
phase. Compare wlLh
mensLrual cycle: 1he mosL varlable phase ls Lhe prollferaLlve phase (noL Lhe secreLory
phase). 1he prollferLlve phase varles wlLh sLress, however, once ovulaLlon has occurred,
lL ls 14 days. 1herefore, prollferaLlve phase ls analogous Lo C
1
phase of Lhe cell cycle b/c
lL can be shorLer or lengLhened, none of Lhe oLher phases (S, C
2
, and M phase) changes,
16

Lhey sLay Lhe same. 1herefore, ln cancer cells, ones wlLh a longer cell cycle wlll have a
longer C
1
phase, and cancer cells wlLh a shorLer cell cycle wlll have a shorLer C
1
phase.

C
1
phase ls Lhe masLermlnd of everyLhlng. Cyclln dependenL klnase (klnase =
phosphorylaLlon = acLlvaLlon). hosphorylaLlon usually lnvolves sendlng a message Lo
acLlvaLe someLhlng. Clucagon ls a phosphorylaLor, whlle lnsulln ls a dephosphorylaLor.
Clucagon wlll phosphorylaLe proLeln klnase and acLlvaLe lL, whlle lnsulln would
dephosphorylaLe proLeln klnase and lnacLlvaLe lL.

C1 Lo S phase: lnacLlve Cyclln d dependenL klnase: Cyclln d acLlvaLes lL, and C
1
phase
makes cyclln u. Cnce cyclln u ls made ln Lhe C
1
phase, lL Lhen acLlvaLes Lhe enzyme:
cyclln dep. klnase (Lherefore lL ls now acLlve). key area Lo conLrol ln cell cycle: LranslLlon
from C
1
Lo S phase. 8ecause lf you have a muLaLlon and lL goes lnLo S phase, lL Lhen
becomes dupllcaLed, Lhen you have Lhe poLenLlal for cancer. 1wo suppressor genes LhaL
conLrol Lhe LranslLlon: (1) 8b suppressor gene: locaLed on chromosome 13, whlch
makes Lhe 8b proLeln, whlch prevenLs Lhe cell from golng from Lhe C
1
Lo Lhe S phase. ln
general, Lo go from C
1
Lo S, Lhe acLlve cyclln dep klnase phosphorylaLes Lhe 8b proLeln,
when lL ls phosphorylaLed=acLlvaLlon, lL can go from Lhe C
1
phase Lo Lhe S phase. A
problem occurs lf Lhere ls a muLaLlon. 1herefore Lhe enzyme ls checked by (2) p33
suppressor gene: locaLed on chromosome 17, whlch makes a proLeln producL LhaL
lnhlblLs Lhe cyclln d dep klnase. 1herefore, lL cannoL go lnLo Lhe S phase, p33 ls Lhe
number 1, mosL lmp gene LhaL regulaLes human cancer.

Lxample: Pv lnacLlvaLes 8b suppressor gene and p33 suppressor gene. Pv makes
Lwo genes producLs L6 (whlch knocks off Lhe p33) and L7 (whlch knocks of Lhe 8b
suppressor gene).

lf you have a polnL muLaLlon Lhe 8b suppressor gene, Lhe 8b suppressor gene ls knocked
off, Lhere wlll be no 8b proLeln, and Lhe cell wlll progress Lo Lhe S phase b/c lL ls
unconLrolled. 1hls muLaLlon ln Lhe 8b suppressor gene predlsposlng Lo many cancers,
C
Lrlangle sunbursL appearance on x-rays), and breasL cancer (8b suppressor can be
lnvolved). uependlng on Lhe age brackeL, lL hlLs ln dlfferenL areas. lf you knock of p33
suppressor gene: Lhe klnase wlll be always acLlve, lL wlll always phosphorylaLe Lhe 8b
proLeln, and LhaL means LhaL lL wlll always go lnLo Lhe S phase, and Lhls ls bad. lf you
knock off any of Lhose genes, Lhe cell wlll go lnLo Lhe S phase. 1he p33 suppressor gene
ls Lhe guardlan of Lhe genome, b/c lL glves Lhe cell Llme Lo deLecL lf Lhere are any
defecLs/abnormallLles ln Lhe unA (spllclng defecLs, codon Lhlng, whaLever, eLc). unA
repalr enzymes can spllce ouL Lhe abnormallLy, correcL lL, and Lhe cell ls ready Lo go Lo
Lhe S phase. lf Lhe cell has Loo much damaged unA, Lhen lL ls removed by apopLosls.
17

1herefore Lhls gene ls lmp b/c lL glves Lhe cell an opporLunlLy Lo clean lLs unA before
golng lnLo Lhe S phase.

2. S phase = synLhesls phase, where everyLhlng ls doubled, lncludes unA and
n n l
number of conLracLlle elemenLs.

3. C
2
phase = where Lubulln ls made (lmp Lo mlcroLubule of Lhe mlLoLlc splndle), lL ls
blocked by eLoposlde and bleomycln.

4. M phase = mlLosls, where Lhe cell dlvldes lnLo Lwo 2n cells. 1he cell can elLher go
lnLo Lhe C
o
resLlng phase, or can conLlnue dlvldlng ln Lhe cycle, or can be permanenLly
dlfferenLlaLed. p33 gene makes a proLeln Lo lnhlblL Lhe klnase, Lherefore prevenLs Lhe
8b proLeln from belng phosphorylaLed, Lherefore sLays ln Lhe C
1
phase. 1herefore, when
you knock lL off, no one ls lnacLlvaLlng Lhe klnase, and Lhe cell ls consLanLly
phosphorylaLed and LhaL keeps Lhe cell dlvldlng, and Lhen has Lhe poLenLlal Lo lead Lo
cancer.

C. Drugs that act on the ce|| cyc|e:

1. urugs acLlng on S phase:
a) LrgoL alkalolds work on Lhe mlLoLlc splndle ln S phase
b) MeLhoLrexaLe works ln S phase: Lxample: pL wlLh rheumaLold arLhlrlLls has
macrocyLlc anemla. urug responslble for Lhls ls ln whaL phase of Lhe cell cycle? S
phase b/c lL ls meLhoLrexaLe blocklng dlhydrofolaLe reducLase

2. urugs acLlng on C
2
phase:
a) LLoposlde
b) 8leomycln

3. urugs acLlng on M phase:
a) Creslofulvln ln M phase
b) acllLaxel speclflcally works ln Lhe M phase: Cllnlcal scenarlo: Lhls drug ls a
chemoLherapy agenL made from a yew Lree? acllLaxel (m phase)
c) vlncrlsLlne and vlnblasLlne
d) 1hls drug used Lo be used for Lhe LreaLmenL of acuLe gouLy arLhrlLls buL b/c of all
Lhe slde effecLs ls no longer used. WhaL drug and where does lL acL? Colchlclne (m
phase)

18

4. Cllnlcal scenarlo LhaL does noL work on Lhe cell cycle Plv
and whlLe ouL of Lhe lung, on a drug, ends up wlLh cyanosls, whlch drug? uapsone
19

VII. Adaptat|ons to env|ronmenta| stress: Growth a|terat|ons

A. Atrophy: ulagnosls: Lhe decrease ln Llssue mass and Lhe cell decreases ln slze. 1he cell
has [usL enough organelles Lo survlve, le less mlLochondrla Lhen normal cells, Lherefore, [usL

1. Lxample: hydronephrosls, Lhe compresslon aLrophy ls causlng Lhlnnlng of corLex and
medulla, MCC hydronephrosls ls sLone ln Lhe ureLer (Lhe pelvls ls dllaLed). CuesLlon can
be asked whaL klnd of growLh alLeraLlon can occur here. Answer ls aLrophy b/c of Lhe
lncreased pressure on Lhe corLex and Lhe medulla and produces Lo lschemla, blood flow
decreases and can produce aLrophy of renal Lubules.

2. Lxample: ALrophled braln due Lo aLherosclerosls (MC) or degeneraLlon of neurons
(alzhelmers, relaLed Lo beLa amylold proLeln, whlch ls Loxlc Lo neurons).

3. Lxample: ln muscle, many causes of aLrophy L C u
sclerosls) knock off neurons Lo Lhe muscle, so lL ls noL sLlmulaLed, leadlng Lo aLrophy.

4. Lxample: Lndocrlne relaLed:
a) PypoplLulLarlsm wlll lead Lo aLrophy of adrenal corLex: Lhe zona faslculaLa and
reLlucularls layers of Lhe adrenal corLex, nC1 Lhe glomerulosa b/c AC1P has noLhlng
Lo wlLh sLlmulaLlng aldosLerone release. 1he faslculaLa ls where glucocorLlcolds
(corLlsol) are made, whlle reLlcularls ls where sex hormones are made (17
keLosLerolds and LesLosLerone). AC1P ls responslble for sLlmulaLlng Lhese, Lherefore
zona faslculaLa and zona reLlcularls are aLrophled.

b) 1aklng Lhyrold hormone wlll lead Lo aLrophy of Lhyrold gland. 1hls ls due Lo a
decrease of 1SP and Lherefore noLhlng ls sLlmulaLlng Lhe Lhyrold gland whlch leads Lo
aLrophy.

3. Lxample: Sllde showlng a blopsy of a pancreas ln a paLlenL wlLh cysLlc flbrosls. WhaL
ls growLh alLeraLlon? ALrophy, b/c Lhe Cl18
problems wlLh secreLlons. 1he secreLlons become Lhlcker and as a resulL, lL blocks Lhe
ducLs and so LhaL means LhaL Lhe glands LhaL were maklng Lhe flulds (Lhe exocrlne parL
of Lhe gland) cannoL make flulds b/c of Lhe back pressure blocklng Lhe lumen of Lhe
ducL, whlch leads Lo aLrophy of Lhe glands, whlch Lhen leads Lo malabsorpLlon ln all
chlldren wlLh cysLlc flbrosls.

6. Lxample: Sllde of an aorLa, wlLh aLheroscleroLlc plaque, whlch leads Lo aLrophy of
Lhe kldney and secondary P1n (renovasuclar P, leadlng Lo hlgh renln level comlng ouL
20

of Lhe kldney). ln Lhe oLher kldney, lL ls overworked, Lherefore Lhere ls hyperLrophy
(renln level comlng ouL of Lhls veln ls decreased and suppressed).

8. nypertrophy lncrease of Lhe SlZL of cell, noL number
Scenarlo: A cell blology quesLlon: whaL ls Lhe n of Lhls?
PyperLrophy of a cardlac muscle (permanenL muscle), suppose Lhere ls a block [usL
C W A mes ls
4n, b/c lL already underwenL synLhesls: already doubled.
n
2 n = normal (dlplold cell)
3 n = Lrlsomy
4 n = double Lhe number

C. nyperp|as|a lncrease ln Lhe # of cells
ln normal prollferaLlve gland, Lhere are Lhousands of mlLoses, Lherefore see more glands
wlLh hyperplasla.

1. Lxample leadlng Lo cancer: WlLh unopposed esLrogen, you may end up wlLh cancer,
-counLeracLs Lhe
esLrogen), you wlll geL cancer. 1he cells wlll go from hyperplasla, Lo aLyplcal hyperplasla
Lo endomeLrlal cancer. 1herefore hyperplasla lefL unchecked Lhere ls an lncreased rlsk
of cancer. Cne excepLlon: benlgn prosLaLlc hyperplasla, hyperplasla of Lhe prosLaLe
does nC1 lead Lo cancer, [usL urlnary lnconLlnence.

2. Lxample 1
30 hyperLrophy of Lhe smooLh muscle cells ln Lhe wall of Lhe uLerus, and 30 relaLed
Lo hyperplasla.

3. Lxample: 8one marrow: normally x W8C 88C S
W8C 88C 1 88C 1
expecLed Lo be seen ln lron def anemla nor ln Lhalassemlas b/c ln Lhose, Lhere a defecL
ln Pb producLlon. lL ls expecLed Lo be seen ln chronlc obsLrucLlve pulmonary dz (CCu)
b/c Lhe hypoxemla causes Lhe release of hormone LC (eryLhropoleLln), whlch ls made
ln Lhe endoLhellal cells of Lhe perlLubular caplllarles. So ln Lhe sllde Lhls ls an example of
LC sLlmulaLed marrow.

4. Lxample: psorlasls on elbow an example of hyperplasla (unregulaLed prollferaLlon
of squamous cells ln Lhe skln), leadlng Lo red skln, and ralsed red plaque, b/c excesslve
1 speclflc for
Lhe S phase, and prevenLs Lhe basal cells from prollferaLlng.
21


3. Lxample: prosLaLe gland and bladder hyperplasla of prosLaLe glands, lL a hormone
relaLed hyperplasla, all hormone sLlmulaLed glands undergo hyperplasla, noL
hyperLrophy. 1he wall of Lhe bladder ls Loo Lhlck, b/c urlne has Lo go ouL Lhru a narrow
openlng ln Lhe ureLhra, Lherefore Lhe muscle has Lo work harder whlch leads Lo
hyperLrophy of smooLh muscle cells of Lhe bladder wall (more urlne musL go ouL agalnsL
a greaLer force b/c of an lncrease ln afLer load).

D. Metap|as|a replacemenL of one adulL cell Lype by anoLher

1. Lxample: Sllde of an esophagus, parL of lf ls all ulceraLed away. Cn a secLlon
surroundlng Lhe ulcer (rlghL aL Lhe edge of Lhe muscosa) Lhere are mucous secreLlng
cells and gobleL cells (Lhese are grandular cells). 1hese cells are noL supposed Lo be
presenL ln lower esophagus, squamous cells should be Lhere (noL glandular cells).
MeLasLaLlc grandular: 8arreLs esophagus ls a precursor for adenocarclnoma.
Adenocarclnoma has surpassed squamous cell carclnoma of mld-esophagus as Lhe MC
cancer of Lhe esophagus. 1herefore, CL8u ls Lhe number one precursor Lo esophageal
cancer (adenocarclnoma).

Audlo flle 4: lnflammaLlon 2

2. Lxample: Llnlng of malnsLem bronchus clllaLed columnar, pseudosLaLlfled columnar.
ln smokers, Lhls would be an example of meLaplasla would be squamous.

3. Lxample: 1here are lncreased gobleL cells wlLhln malnsLem bronchus of an old
smoker, also see gobleL cells ln Lhe Lermlnal bronchlal. normally Lhere are gobleL cells
ln Lhe malnsLem bronchus buL Lhere are no gobleL cells ln Lhe Lermlnal bronchus,
Lherefore Lhls ls an example of hyperplasla.

4. Lxample: CobleL cells ln Lhe sLomach are abnormal (should be ln Lhe lnLesLlnes, only).
1hls ls a glandular meLaplasla, whlch ls a precursor for adenocarclnoma of Lhe sLomach.
P. pylorl are a precursor for adenocarclnoma ln Lhe sLomach. 8/c P. pylorl causes
damage Lo pylorus and anLral mucosa b/c lL ls a chronlc gasLrlLls whlch lnLesLlnal
glandular meLaplasla, whlch ls a precursor for adenocarclnoma. MCC adenocarclnoma
of Lhe sLomach = P. pylorl.

3. Lxample: Cases where meLaplasla causes an lncreased rlsk Lo caner:

a) 8emember LhaL lf hyperplasla ls lefL unchecked, could poLenLlally lead Lo cancer.
lor example: ln endomeLrlal hyperplasla Lhe MC precursor leslon Lo endomeLrlal
22

carclnoma due Lo unopposed esLrogen. 1he excepLlon ls prosLaLlc hyperplasla, whlch


b) MeLaplasla can also go Lhrough a process leadlng Lo cancer:

(1) ln lung, clllaLed columnar eplLhellum 8LCCMLS squamous, Lherefore, Lhls ls
called SCuAMCuS meLaplasla, Lhls wlll lead Lo squamous dysplasla, whlch Lhen
proceeds Lo cancer (squamous carclnoma),

(2) ln dlsLal esophagus, wenL from squamous Lo glandular eplLhellum b/c
squamous eplLhellum cannoL handle Lhe acld, Lherefore lL needs mucous
secreLlng eplLhellum as a defense agalnsL cellular ln[ury. Powever, Lhe glandular
meLaplasla can go on Lo an aLyplcal meLaplasla, predlsposlng Lo adenocarclnoma
of Lhe dlsLal esophagus.

(3) araslLes: 2 paraslLes produce cancer: clonesls slnesls leads Lo
cholanglocarclnoma (Chlnese llver fluke), and shlsLosoma hemaLoabla. 1he
schlsLosomlas hemaLobla causes bladder cancer by causlng Lhe LranslLlonal
eplLhellum Lo undergo squamous meLaplasla. 1hls leads Lo squamous dysplasla,
and Lhen on Lo squamous cancer. 1ranslLlonal eplLhellum leads Lo squamous
eplLhellum (called meLaplasla), Lhen dysplasla, Lhen on Lo cancer.

L. Dysp|as|a ls really an aLyplcal hyperplasla.

1. Lxample: Sllde of a squamous eplLhellum ls dlsorganlzed, wlLh nuclel LhaL are
larger near Lhe surface and Lhe basal cell layer ls responslble for Lhe dlvldlng, cells aL
Lop are blgger Lhan Lhe ones LhaL are dlvldlng, lL has lack orlenLaLlon. lf lL was found
durlng a cervlcal blopsy ln pL wlLh Pv lnfecLlon, or lf lL was found ln Lhe malnsLem
bronchus blopsy, you should be able Lo Lell LhaL lL ls dysplasLlc. 1herefore dysplasla,
wheLher glandular or squamous, ls a precursor for cancer.

2. Lxample: 1here was a farmer wlLh leslon on Lhe back of hls neck (can grow on any
parL of Lhe body, due Lo sun exposure), whlch could be scraped off and grew back
acLlnlc keraLosls (aka solar keraLosls) ls a precursor for sq. cell carclnoma of Lhe
skln. uv-b llghL damages Lhe skln. AcLlnlc keraLosls does noL predlspose Lo basal cell
carclnoma, even Lhough basal cell carclnoma ls Lhe mosL common skln cancer.
23

CnA1Lk 1WC: INILAMMA1ICN

I. Acute Inf|ammat|on

A. Card|na| s|gns of |nf|ammat|on
ln Lhe scenarlo wlLh a bee sLlng: you wlll see redness (1ubor). 1he klng of vasodllaLors ls
hlsLamlne and lL vasodllaLes Lhe arLerloles. 1herefore, hlsLamlne ls responslble for Lhe
redness of acuLe lnflammaLlon (le bee sLlng), and ls worklng on arLerloles. now lf we
felL Lhe area, lL wlll be warm (Ca|or = heaL), Lhls ls due Lo vasodllaLlng Lhe arLerloles,
whlch ls caused by hlsLamlne. lor example ln endoLoxlc and sepLlc shock, Lhe skln ls
warm b/c you are vasodllaLed. 1umor ls a ralsed sLrucLure caused by hlsLamlne.
PlsLamlne can lead Lo lncreased vessel permeablllLy ln Lhe venules, ls arLerlal Lhlcker
Lhan venules? ?es. 1he venules are very Lhln, Lhey baslcally have an endoLhellal cell
wlLh a basemenL membrane, all you have Lo ls drlll a hole Lhrough Lhe 8M and you are
ouL. 1herefore, lncreased vessel permeablllLy occurs aL Lhe venule level, noL Lhe arLerlal
level. PlsLamlne conLracLs Lhe endoLhellal cells, and leaves Lhe 8M bare, leadlng Lo
lncreased vessel permeablllLy, produclng an exudaLe, and swelllng of Llssue, hence
tumor of acuLe lnflammaLlon. 1he area may hurL (Do|or = paln) buL hlLamlne does noL
have anyLhlng Lo do wlLh Lhls. 8radyklnln ls parL of Lhe klnlnogen sysLem beLween
facLor 11 and Pageman facLor 12. So when you acLlvaLe Lhe lnLrlnslc paLhway, you
auLomaLlcally acLlvaLe Lhe klnlnogen sysLem. When you acLlvaLe facLor 12 (Pageman
facLor), lL wlll acLlvaLe 11 and Lhe whole klnlnogen sysLem. 1he end producL ls
bradyklnln. ACL degrades bradyklnln. CompllcaLlon of ACL lnhlblLor ls angloedema.
Also lnhlblL meLabollsm of bradyklnln, whlch lncreases vessel permeablllLy, produclng
Lhe angloedema (swelllng of Lhe Llssues). Pow bradyklnln produces cough ls noL really
undersLood. 8radyklnln and CL2 cause paln (do|or) and ls Lhe only one ouL of Lhe four
LaLln Lerms of acuLe lnflammaLlon LhaL ls noL due Lo hlsLamlne release.

8. Steps |nvo|ved |n Acute |nf|ammat|on (Lhls Lhe normal sequence ln acuLe
lnflammaLlon):
1. LmlgraLlon: lncludes marglnaLlon, paveenLlng, rolllng, adheslon, and LransmlgraLlon
neuLrophlls ln clrculaLlon sLarL Lo become sLlcky b/c of adheslon molecule synLhesls.
LndoLhellal cells begln Lo synLheslze adheslon molecules. LvenLaLually, neuLrophlls
wlll sLlck Lo endoLhellal cells, Lhese sLeps are called pavmenLlng or marglnaLlon. 1hen
neuLrophlls look for bare basemenL membrane on Lhe venules and Lhen Lhey drlll a
hole Lhrough lL vla Lype 4 collagenase. Cancer cells also have Lype 4 collagenase,
C
molecules, usually agalnsL lamlnln ln 8M, and Lhey have collagensae Lo geL Lhrough
Lhe 8M, Lherefore, cancer cells are preLLy much llke a neuLrophll when lnvadlng
Llssue.
24

2. ChemoLaxls:
When Lhey pass 8M of small venules, Lhey emlgraLe buL Lhey have Lo know whaL
dlrecLlon Lo go. 1hey geL dlrecLlons ln a process called dlrecLed chemoLaxls. C3a and
L1-84 (leukoLrlene 84) are Lhe chemoLacLlc agenLs. 1hese chemoLacLlc agenLs are
also lnvolved ln maklng adheslon molecules on neuLrophlls). 1herefore, Lhey make
adheslon molecules Anu glve dlrecLlon by acLlng llke chemoLacLlc agenLs.

3. hagocyLosls vla opsonlzaLlon:
a) Lxample: ln an acuLe lnflammaLlon wlLh sLaph aureus, Lhe bacLerla are belng
processed by opsonlns, whlch lmmoblllze Lhe parLlcles on Lhe surface of Lhe
phagocyLe. 1he Lwo maln opsonlns are lgC and C3b. 1hey help wlLh phagocyLosls.

b) Lxample of an opsonlzaLlon defecL: 8ruLons agammagloblnemla: an x-llnked
recesslve dz, where all Lhe lmmunoglobullns are mlsslng, lncludlng lgC. 1herefore,
MCC deaLh ln Lhese pLs ls due Lo lnfecLlon b/c cannoL opsonlze Lhlngs. lL produces
hypogamma-globlnemla, buL Lhe mechanlsm of lnfecLlon ls due Lo noL havlng lgC Lo
opsonlze bacLerla, Lherefore cannoL phagocyLose lL.

8acLerla are opsonlzed by lgC and C3b, whlch means LhaL neuLrophlls musL have
recepLors for Lhose. ln acuLe lnflammaLlon Lhe maln cell ls neuLrophll and ln chronlc
lnflammaLlon Lhe maln cell ls macrophage/monocyLe (monocyLes become
macrophages). 1hese cells have Lo have recepLors for Lhese opsonlns (lgC and C3b).
1hen Lhey become phagocyLosed or become phagolysomes. When Lhey are
phagocyLosed, Lhe lysosomes go Lo mlcroLubules and empLy Lhelr enzyme lnLo Lhls.

c) Lxample: ln l-cell dlsease: ln Lhls dz, mannose resldues cannoL be phosphorylaLe
ln golgl apparaLus Lherefore Lhe enzymes are noL marked wlLh phosphorus, and Lhe
lysosome are empLy.

4. lnLracellular mlcroblal kllllng:
a) Lxamples:
(1) SLaph aureus ln hoLLub surrounded by enzymes
(2)Chlamydla can geL ouL of phagolysosome, mechanlsm unknown, buL
someLlmes Lhey have mucous and all klnds of Lhlngs around Lhem.
b) C
2
dependent mye|operox|dase system ls Lhe boards!!
Molecular C
2
ls converLed by nAuP oxldase, whlch ls ln Lhe cell membrane of
neuLrophlls and monocyLes, buL noL macrophages. 1he mosL lmporLanL cofacLor ls
nAuP, whlch ls synLheslzed ln Lhe penLose phosphaLe shunL. 1he enzyme
responslble ls glucose 6 phosphaLe dehydrogenase, whlch converLs C6 lnLo 6-
25

phosphogluconaLe, generaLlng nAuP and a neuLrallzlng facLor for free radlcals
(gluLaLhlone).

lL ls converLlng C
2
lnLo a free radlcal, superoxlde. Superoxlde has an unpalred
elecLron glvlng off energy, whlch ls called a resp bursL, whlch can be measured by
radlaLlon deLecLors, and by a negaLlve n81 dye LesL. ln Lhe n81 LesL, you have a LesL
Lube, add Lhe colorless n81 dye, and lf neuLrophlls and monocyLes are worklng
normally, Lhey wlll phagocyLose lL, wlll have a resplraLory bursL, and Lhe free radlcal
C
2
wlll cause Lhe color Lo change Lo blue, lndlcaLlng LhaL Lhe resp bursL ls worklng. lf
Lhere ls no color change, Lhere ls noL a resp bursL, Lherefore Lhe pL has chronlc
granulomaLous dz of chlldhood.

lree radlcal C
2
SCu . eroxlde lLself
could klll bugs, buL lL ls used for anoLher reason. WlLhln Lhe neuLrophlls and
monocyLes are reddlsh granules whlch are lysosomes, and are seen ln Lhe perlpheral
blood. Myeloperoxldase (one of Lhe many enzymes ln Lhe granules) wlll caLalyze Lhe
rxn. lL wlll comblne peroxlde wlLh chlorlde Lo from bleach. 1hls |s the most potent
bacter|c|da| mechan|sm C
2
dep mye|operox|dase system, whlch ls ln
nLu18CPlLS and MCnCC?1LS buL nC1 ln macrophages, b/c macrophages lose Lhe
sysLem when Lhey converL from monocyLes Lo macrophages and Lhey use lysosomes
Lo klll. Macrophages of Lhe CnS are mlcrogllal cells, so Lhe reservolr cell for
CnS/AluS ls Lhe mlcroblal cell. CuLslde Lhe CnS, lL ls Lhe dendrlLlc cell, lL ls a
macrophage locaLed ln Lhe lymph nodes.

c) ln C6u deflclency, lnfecLlon ls Lhe MC preclplLaLlon of hemolysls b/c Lhere ls no
nAuP, Lherefore Lhere ls no funcLlonlng C
2
dependenL myeloperoxldase sysLem,
88CS

d) Chronlc granulomaLous dz of chlldhood = x llnked recesslve dz where Lhe mom
glves Lhe dz Lo Lhe boy, and ls an asympLomaLlc carrler, and Lhey wlll LransmlL Lhe dz
l nAuP oxldase, and
n81 ow color of dle), Lherefore no resp bursL. uo
Lhey have superoxlde? no. eroxlde? no. Myeloperoxldase? ?es. Chlorlde? ?es.
1herefore, lf Lhey phagocyLosed a bacLerla LhaL could make peroxlde, and add lL
lnslde Lhe phagolysosome, Lhls ls whaL Lhe kld would need Lo klll Lhe bacLerla. 1hese
klds are mlsslng L8CxluL b/c Lhere ls no nAuP oxldase. ALL llvlng organlsms make
peroxlde (lncludlng ALL bacLerla). Powever, noL all bacLerla conLaln caLalase, whlch
ls an enzyme LhaL breaks down peroxlde. So, ln chronlc granulomaLous dz, whaL can
C W 8
C CA1
26

lL wlll also make caLalase and neuLrallze lL, Lherefore Lhe chlld cannoL klll sLaph, and
wlll klll Lhe kld. lf lL was a sLrepLococcus organlsm LhaL makes peroxlde (does noL
have caLalase Lherefore peroxlde can be used by Lhe chlld), lL adds whaL kld really
needed Lo make bleach, and Lhe bacLerla ls Lhen wlped ouL. 1herefore, can klll sLrep
and noL sLaph!

e) Myeloperoxldase deflclency: uo Lhey have a resp bursL? ?es b/c Lhey have nAuP
oxldase. uo Lhey have peroxlde? ?es. uo Lhey have superoxlde free radlcals? ?es. uo
Lhey have chlorlde? ?es. uo Lhey have myeloperoxldase? no. 1hey have a normal
n81 cannoL
make bleach. 1hls ls called a myeloperoxldase defecL. CLher Lypes of defecLs: (1)
opsonlzaLlon defecLs wlLh bruLons (mlssln lC C
where cells do noL respond Lo chemoLaxls, (3) mlcroblocldal defecLs, Lhe defecL ln
Lhe abllllLy Lo klll bacLerla, example: chronlc granulmaLous dz of chlldhood and
myeloperoxldase deflclency are boLh mlcroblocldal dz, ln LhaL Lhey cannoL klll
bacLerla, buL for dlfferenL reasons. ln myeloperoxldase def Lhe problem ls LhaL Lhey
cannoL make bleach (b/c of Lhe mlsslng enzyme), buL do have resp bursL, and ls
AuLosomal recesslve dz. ln CCuz Lhe problem ls LhaL Lhey cannoL make bleach
elLher, buL Lhey have an A8SLn1 resp bursL, and ls a x-LlnkLu recesslve dz.

C W
removed and looked aL hlsLologlcally, Lhey dld noL see neuLrophlls ln Lhe Llssue or
neuLrophlls llnlng Lhe small vessels. 1hls ls an adheslon molecule defecL or beLa 2
lnLegrln defecL. umblllcal cord needs Lo have an lnflammaLory rxn lnvolvlng
1
Lhls ls a
classlc adheslon molecule defecL.

C. Chem|ca| med|ators:
1. PlsLamlne: Lhe klng of chemlcal medlaLors of acuLe lnflammaLlon
a) WhaL does lL do Lo arLerloles? vasodllaLes
b) venules? lncreased vessel permeablllLy

2. SeroLonln:
a) WhaL amlno acld makes seroLonln? 1rypLophan
b) ls seroLonln a neuroLransmlLLer? ?es
c) ln a deflclency, you geL depresslon (also decreased nL)
d) a vasodllaLor and lncreases vascular permeablllLy

27

3. ComplemenL sysLem: AnaphylaLoxlns C3a, C3a. luncLlon: sLlmulaLe masL cells Lo
release hlsLamlne, leadlng Lo vasodllaLlon and lncreased vessel permeabllllLy. 1hey also
play a role ln shock, b/c when Lhere ls lnflammaLlon Lhe compllmenL sysLem ls acLlvaLed,
Lherefore Lhere wlll be masL cells and hlsLamlne, Lherefore C3a, and C3a wlll boLh be
Lhere.

4. nlLrlc oxlde made malnly ln endoLhellal cells, and ls a poLenL vasodllaLor. lL ls used
for LreaLlng pulmonary hyperLenslon. lL has a blg Llme role ln sepLlc shock.

3. lL-1 assoclaLed wlLh a fever, lL ls a pyrogen, Lherefore sLlmulaLes Lhe hypoLhalamus Lo
C A
by lnhlblLlng Lhe synLhesls of prosLaglandlns Lhereby reduclng Lhe fever.

6. Arachldonlc acld meLabollLes:
a) CorLlcosLerolds lnhlblLs hosphollpase A
2
, Lherefore do noL release arachldonlc
C 1
supreme anLlflammaLory agenL 8C1P C
blocklng phosphollpase A
2
. Arachldonlc aclds make llnolelc acld (omega 3), whlch ls
found ln flsh olls and walnuLs. lL ls very good for you b/c lL acLs llke asplrln, and
s how omega 3 proLecLs your hearL.

b) Llpoxygenase paLhway: ZlleuLln blocks 3-llpoxgenase, oLher drugs acL by blocklng
Lhe recepLors, example: zlrkufulasL, eLc. LeukoLrlene (L1) C4, u4, L4 (Lhe slow reacLor
subsLances of anaphylaxls) seen ln bronchlal asLhma. 1hey are poLenL
bronchoconsLrlcLors, Lherefore lL can be seen why zlleuLln works well ln asLhma b/c lL
blocks Lhe leukoLrlenes, lncludlng Lhese (L1-C4, u4, and L4). L1 84 ls an adheslon
molecule ln chemoLaxls.

c) Cyclooxygenase paLhway: Asplrln blocks cycoloxygenase, lrreverslbly ln plaLeleLs.
CP2: where everyLhlng seems Lo be derlved from. Cl2: derlves from endoLhellal
prosLacyclln synLhase, ls a vasodllaLor and lnhlblLs plaLeleL
aggregaLlon (exacL Lhe opposlLe of 1xA2). 1hrombaxane A2 (Lhe enemy of Cl2) ls

plaLeleL aggregaLlon. WhaL drug blocks Lhrombaxane synLhase and ls used Lo sLress
LesLlng for CAu? ulpyrramldal blocks Lhe enzyme, 1xA2 synLhase, Lherefore does noL
have Lo perform a Lreadmlll sLress LesL, all you have Lo do ls use Lhe drug
dlpyrramldal.
CL2: vasodllaLor ln kldney, keeps paLenL ducLus paLenL ln baby hearL, makes Lhe
mucous barrler ln Cl (sLomach) Lhereby prevenLlng ulcers, can cause dysmenorrhea
28

woman and lncreased uLerlne conLracLlllLy, and lL an aborLlfacLanL, Lo geL rld of feLal
maLerlal.

d) CCx 2-make sure you know how Lhls works!

e) CorLlcosLerolds blocks phosphollpase A2, and lL also decreases adheslon molecule
synLhesls, along wlLh oLher sLerolds llke eplnephrlne and nL. uecreased adheslon
molecule synLhesls, wlll lead Lo lncreased neuLrophlls on C8C, ln lmmuno, 30
neuLrophlls are sLuck Lo Lhe endoLhellal vessels, and Lhe oLher 30 are clrculaLlng,
Lherefore, decreaslng adheslon molecule synLhesls wlll lead Lo doubled W8C (b/c Lhe
30 of neuLrophlls LhaL were sLuck are now clrculaLlng). CorLlcosLerolds desLroy 8-
M W8C 8 1
apopLosls, Lherefore, corLlcosLerolds are Lhe slgnal Lo acLlvaLe Lhe caspasases.
Loslnophlls, malnly seen ln Lype one P? rxn, corLlcosLerolds decrease Lhem. When
on corLlcosLerolds, Lhe only Lhlng LhaL ls lncreased ls neuLrophlls, vla decreased
adheslon molecule synLhesls. LymphocyLes and eoslnophlls are decreased. Lxample:
lf have Addlsons, do noL have corLlsol, Lherefore Lhe neuLrophll cL decreases and Lhe
eoslnophll counL wlll lncrease. Lxample: a person wlLh Ml wlLh an 18,000 C8C mosL
of whlch are neuLrophlls. Mechanlsm: Lplnephrlne decreases adheslon molecule
syLhesls and neuLrophll counL goes up.

D. L|ectron m|croscopy of |nf|ammatory ce||s:
1. ln lung, Lype ll pneomocyLe (black doLs are lysosomes).
Lamellar bodles sLrucLures where leclLhln and phosphoLldyl chollne ls locaLed, lf ask
where macrophage, ls, wlll ask whlch makes surfacLanL.

2. MonocyLe: slngle nucleus wlLh a graylsh cyLoplasm has scavaged, can form foam
LuL ls a free
radlcal), vlL L neuLrallzes oxldlzed LuL.

3. LymphocyLe all nucleus and scanL cypLoplasm, prob a 1 cell (60 of perlpheral
blood lymphocyLes are 1 cells), raLlo of helper Lo suppressor: Cu4:Cu8 ls (2:1),
Lherefore, more llkely Lo be a Pelper 1 cell, Lhen a suppressor 1-cell, and 8 cells (20)
are leasL llkely.

8L8 l
(Lherefore lL ls a plasma cell). MulLlple myeloma has eccenLrlcally locaLed nucleus,
cyLoplasm ls always sky blue, maklng plasma cells ez Lo recognlze. lasma cells are
derlved from 8 cells, and locaLed ln Lhe germlnal folllcle.

29

3. Cranules eoslnophll 88C have crysLals ln Lhe
granules. Loslnophlls are Lhe only lnflammaLory cell LhaL has crysLals ln Lhe granules.
1hey are called CharcoL-L
paLlenL. 1hey are degeneraLed eoslnophlls ln spuLum of asLhmaLlc, and have formed
crysLals LhaL look llke spear heads. 8asophlls have granules LhaL are more purpllsh and
darker, whlle basophlls have darker colors.

6. Mech for kllllng lnvaslve helmlnLhes1ype ll P?ma[or baslc proLeln ls lnvolved.
8 lL A Loslnophlls have lgL
recepLors, Lherefore, eoslnophlls hook lnLo Lhe lgL recepLor and release chemlcals, Lhe
maln one released ls ma[or baslc proLeln, whlch desLroys Lhe helmlnLh, whlch ls Lype ll
P?, b/c lL ls a cell hooklng lnLo an Ab on Lhe LargeL cell. 1he effecLor cell ls 1ype ll P?
rxn ls Lhe eoslnophlls 1ype l P? rxn where Lhe effecLor cell ls
Lhe MAS1 CLLL, and Lhey release hlsLamlne (an eoslnophll chemoLacLlc facLor), Lherefore
Lhey are lnvlLed Lo area of Lype l P? b/c Lhey have hlsLamlnase and arylsulfaLase, whlch
neuLrallzes leukoLrlenes. 1he purpose of eoslnophlls ln Lype l P? ls Lo knock off
chemlcal medlaLors produced ln rxn, however, when an eoslnophll kllls an lnvaslve
helmlnLh, lL does so vla Lype ll P?.

L. C|uster des|gnat|ons:
Pelper L cell = Cu4
CyLoLoxlc 1 cell = Cu8
Marker for Ag recognlLlon slLe for all 1 cells ls Cu3
M Cu
Marker for MC leukemla ln chlldren = Cu10 (calla Ag), poslLlve 8-cell lymphoma
Cu13 and 30 = 8S cell
Cu21, Cnly on 8 cells LpsLeln barr vlrus, hooks lnLo Cu21 on 8 cells, and acLually Lhe
aLyplcal lymphocyLes are noL 8-cells buL 1-cells reacLlng Lo Lhe lnfecLed 8-cells.
8urklLLs ls a 8 cell lymphoma
Cu43 ls found on all leukocyLes, ls a common anLlgen on everyLhlng

I. Iever lL-1 ls responslble and CL2 (Lhls ls whaL Lhe hypoLhalamus ls maklng) whlch
sLlmulaLes Lhe LhermoregulaLory cenLer. lever ls good! lL rlghL shlfLs Lhe C
2
dlssoc curve.
Why do we wanL more C
2
ln Lhe Llssues wlLh an lnfecLlon? 8/c of C
2
dependenL
1
mechanlsm of geLLlng C
2
Lo neuLrophlls and monocyLes Lo do whaL Lhey do besL. Also, hoL
Lemps ln Lhe body are noL good for reproducLlon of bacLerla/vlruses.

II. 1ypes of |nf|ammat|on (scenar|os)

30

A. posL parLum woman, wlLh pus comlng ouL of lacLlferous ducL Lhls ls sLaph aureus
suppleraLlve lnflammaLlon

8. 8one of chlld wlLh sepsls, on Lop of Lhe bone, was a yellowlsh area, and lL was an abscess
osLeomyellLls sLaph. aureus, lf Lhe kld had slckle cell, lL ls salmonella, why aL meLaphysls
of bone? 8/c mosL of blood supply goes here, Lherefore, mechanlsm of spread ls
hemaLogenous (Lherefore comes from anoLher source, and Lhen lL geLs Lo bone).

C. PoL, spread over face cellullLls due Lo sLrep (play odds!) group A pyogenes
(called eryslpllls, anoLher name for cellullLls)

u. ulphLherla = psuedomembrane (corynebacLerlum dlphLherla), a gram + rod, LhaL makes
an exoLoxln, messlng up rlbosylaLlon of proLlens vla elongaLlon facLor 2, Lhe Loxln damages

produces a Loxln LhaL damages Lhe membrane, closLrldlum dlfflclle also does Lhls. lL also
produeces a pseudomembrane and a Loxln, whlch we measure ln sLool Lo make Lhe dx.
1herefore, Lhe answer ls C. dlfflcle.

L. llbrlnouls perlcardlLls, usually wlLh lncreased vessel permeablllLy, seen ln (1)lupus,
leadlng Lo frlcLlon rub, also seen ln (2) Lhe flrsL week of Ml, and Lhen agaln 6 weeks laLer ln
C

l. MC organlsm produclng lnfecLlon ln Lhlrd degree burns = pseudomonas aurlglnosa. Color
of pus: green due Lo pyocyanln.

C. 8asal cell layer on boLh sldes of cloL, prollferaLe, and go underneaLh lL Lo cloL. ln a
k
prescence of granulaLlon Llssue. llbronecLln ls a very lmporLanL proLeoglycan and ls
lnvolved ln Lhe heallng of Lhe wound. llbronecLln ls an lmporLanL adheslon agenL and
chemoLacLlc agenL, lnvlLlng flbroblasL ln helplng heallng process. 1he granulaLlon Llssue
sLarLs aL day 3 and ls on lLs prlme by day 3. lf you ever plcked aL a scar and lL bleed llke mad
and you Lry L n
Llssue means no heallng of a wound. 1ype of collagen ln lnlLlal sLage of wound repalr = Lype
3, Lype 4 collagen seen ln 8M, Lype 1 very sLrong Lenslle sLrengLh, seen ln bone, skln,
Lendons, llgamenLs.

AfLer a few monLhs, afLer monLhs, Lhe collagen Lype 3 ls broken down by collagenases, and
a meLalllc enzyme converLs Lype 3 lnLo Lype 1. Zlnc ls parL of Lhe meLalllc enzyme, Lhls ls
why ln a pL wlLh zlnc deflclency has poor wound heallng b/c lL screws up Lhe collagenase
31

(musL replace Lype 3 wlLh Lype 1). Max Lenslle sLrengLh afLer 3 monLhs = 80. MCC poor
wound heallng = lnfecLlon

P. Lhlers uanlos defecL ln collagen due Lo syn/breaklng down, have poor wound heallng.

l. marfan defecL ln flbrllln, also have poor wound heallng

!. L wlLh scurvy prollne and lyslne vla ascorblc acld.
8
sLrengLh? Crossbrldges. When you crossbrldge Lhlngs, Lhey anchor lnLo areas where you
have hydroxylaLed prollne and lyslne. 1herefore have weak abnormal collagen ln scurvy b/c
Lhere are no crossbrldges Lo aLLach, leadlng Lo noL belng able Lo heal wounds,
hemo

Audlo flle 3: lluld and hemodyn1

k. CranulaLlon Llssue wlLh a loL of blood vessels due Lo loL of flbroblasL C, wlLh
lnflammaLory cells from plasma cells and lymphocyLes, necessary for wound heallng (rlch
vascular Llssue, whlch ls absoluLely essenLlal for normal wound heallng).

L. kelold (hyperLrophlc scar) = excess ln Lype 3 collagen deposlLlon, whlch causes a Lumor
looklng leslons, esp ln blacks. ln a whlLe kld kelold Lo due Lo Lhlrd degree burns. ln
anoLher example: ln a chronlcally dralnlng slnus LracL of Lhe skln, Lhey Lrled Lo puL

dralnlng LracL, and noLhlng worked. WhaL ls lL? 1he answer ls squamous cell carclnoma due
Lo a loL of Lurnover, Lype 3 converLed Lo Lype 1, and flbroblasLs are lnvolved. A loL of cell
dlvlslon occurrlng, whlch can presdlspose Lo muLaLlons and cancer, esp squamous cell
cancer. Squamous cancer ls lmp b/c chronlcally dralnlng slnus LracLs, and predlsposes Lo
sqamous cell carclnoma. Pyperplasla predlsposes Lo squamous cell carclnoma.

III. Chron|c |nf|ammat|on

A. ulfference ln lmmunoglobullns:
1. AcuLe lnflammaLlon: lgM = maln lg flrsL, and Lhen lgC
lgM = maln lg, need a loL of complemenL componenLs ln heallng process, lgM ls Lhe
mosL poLenL acLlvaLor, and have acLlvaLlon of complemenL paLhway (all Lhe way for
1-9), lgM has 10 acLlvaLlng slLes (penLamer).

lgC can acLlvaLe Lhe classlcal sysLem, buL does nC1 go passed C3 and sLops and does
noL go onLo C3-9.
32

AfLer 10 days, Lhere ls lsoLype swlLchlng, and Lhe mu heavy chaln ls spllced ouL (mu
chaln defles speclflclLy of an lg), lL spllces ln a gamma heavy chaln, and lgC ls made
vla lsoLype swlLchlng
2. Chronlc lnflammaLlon: lgC (as maln lg lgM ls coverLed Lo lgC lmmedlaLely)

8. ulfference ln Cell 1ypes:
1. AcuLe lnflammLlons = neuLrophll
2. AcuLe allerglc reacLlons= eoslnophlls (masL cells are ln Llssues)
3. vlral lnfecLlons = lymphocyLes are Lhe maln lnflammaLory cells
4. Chronlc lnflammaLlons = monocyLes/macrophages are lmp. And see a loL of plasma
cells and lymphocyLes, do noL see pus-exudaLlve (Lhls ls ln acuLe lnflamm lncreased
vessel permeablllLy, and lncreased emlgraLlon of neuLrophlls lnLo lnLersLlLlal Llssue, a
proLeln rlch fluld wlLh >3 grams/dL, wlLh a proLeln rlch fluld = pus). Lxample: CholecysLls.

C. 1ype lv PypersenslLlvlLy 8eacLlon:
AnoLher example: Cranuloma = chronlc lnflammaLlon (never acuLe), le caselous
necrosls ln someone wlLh 18, roundlsh, plnk, mulLlnucleaLed glanL cells = granulomas,
paLhogenesls = Lype lv hypersenLlsLlvlLy reacLlon delayed P?. 1he maln acLors are
cyLoxlc 1 cells, when Lhey klll neoplasLlc, vlrally lnfecLed cells, Lhese are also Lype lv P?
A lv P? 8 18
phagocyLoses lL, and Lhere ls lymphohemoLogenous spread, meanwhlle Lhe macrophage
ls processlng Lhe Ag. 1hen afLer weeks, lL presenLs lL Lo helper 1 cells. 1herefore, Lhe
key players ln 1ype lv hypersenslLlvlLy rxn are macrophages whlch process LhaL Ag and
presenLs LhaL Ag vla class ll MPC slLes Lo Lhe helper 1 cells. 1hese helper 1-cells release
cyLoklnes: gamma lln and macrophage lnhlblLory facLor. Camma lln wlll acLlvaLe Lhe
macrophage Lo klll Lhe 18, CrypLococcus, hlsLoplasmosls, eLc. 1herefore Lhe gamma lln
ls Lhe Lrlgger Lo acLlve Lhe macrophage, macrophage cannoL klll wlLhouL Lhe acLlvaLlon
from gamma lln, b/c sysLmemlc fungl and 18 have llpld ln Lhe cell wall, Lhls leads Lo
A epLhllold
macrophages (whlch have been acLlvaLed by gamma lln), when Lhey dle, Lhey dle ln
sLyle Lhey fuse LogeLher and form mulLlnucleaLed glanL cells (llke Lhelr
1herefore, eplLhelold cells are fused macrophages, black doLs are helper 1 cells.
1here are Lwo Lypes of helper 1-cell:
a. SubseL 1: lnvolved ln 1ype lv (delayed Lype) P?, macrophages have lL-12,
when lL ls secreLed, Lhe subseL 1 helper 1 cells are presenLed wlLh Lhe anLlgen,
Lhen, subseL 1 become MLMC8? 1 cells. lL-12 ls lnvolved ln acLlvaLlng Lhe
memory of subseL 1 helper L cells. MosL people ln Lhelr prlmary dz usually
recover wlLh no problems, buL Lhe granulomas can calclfy, as seen on x-ray. A
calclfled granuloma ls noL dead b/c Lhey are reslsLanL Lo dylng. 1herefore, mosL
33

cases of secondary 18 are due Lo reacLlvaLlon 18. Cranulomas necrosls ls due Lo
reacLlvaLlon.

u ln[ecLed lnLo Lhe skln, Lhe macrophage of
Cu whlch have blrbeck
granules-look llke Lennls rackeLs on LM. 1hey phagocyoLose Lhe Ag (Lhe u), and
process lL very qulckly, Lhey presenL lL Lo helper subseL 1, whlch has memory of
prevlous exposure. 1herefore, lL hooks ln Lhe MPC class ll Ag slLes (as all lmmune
A u
Lhe helper 1 cell releases Lhe cyLoklnes produclng Lhe lnflammaLory rxn wlLh
lnduraLlon u

C 1 lv
u
l Alu 1 per 1-
M
keeps macrophages ln LhaL area, Lherefore, wlLh Plv, b/c Lhe helper L cell cL ls
1 MAl
(organlsms) all over Lhe body wlLhouL granulomas b/c helper 1 cells are
W u

IV. 1|ssue kepa|r
Scar Llssue (b/c lLs permanenL Llssue), scar Llssue (flbrous Llssue) does noL conLracL, Lherefore,
lf you have more scar Llssue Lo free wall of lefL veLrlcle wlll lead Lo decreased e[ecLlon fracLlon
(whlch ls sLroke volume dlvlded by Luv).

A. 8esponse of kldneys Lo ln[ury: kldney wlll form scar Llssue, medulla ls mosL suscepLlble
Lo lschemla (b/c leasL amounL of blood supply). WhaL parL of nephron mosL suscepLlble Lo
Llssue hypoxla? 2 places:

1. SLralghL porLlon of prox Lubule b/c mosL of oxldaLlve meLabollsm ls locaLed Lhere,
wlLh brush borders Lhls ls where mosL of reabsorpLlon of na, and reclalmlng of blcarb
ls Lhere.

2. Medullary segmenL of Lhlck ascendlng llmb where Lhe na/k-2Cl pump ls whlch ls
where loop dlureLlcs block. 1he na/k-2Cl pump generaLes free waLer. 1he Lwo Lype of
waLer ln urlne: obllgaLed and free. lf Lhe waLer ls obllgaLed, Lhen Lhe waLer ls obllgaLed
n k C 8
n k C nkC 1 AuP
free waLer b/c Lhe pump generaLes free waLer.
34


L n 20 mls,
k C
reabsorbed whlch ls anoLher 40, Lherefore, for absorblng one na, one k, and 2 C
have Laken 80 mls of free waLer from Lhe urlne Lhls ls free waLer LhaL ls generaLed, lLs
ls Lhls pump LhaL loop dlureLlcs block, whlch ls ln Lhe Lhlck ascendlng llmb of Lhe
medullary segmenL.

8. Lung repalr cell ls Lype ll pneumocyLe (can also repalr Lype l pneumocyLes), lL also
synLheslzes surfacLanL.

C. CnS
neuron), LhaL can prollferaLe and produces proLoplasmlc processes called gllosls (rxn Lo
ln[ury ln Lhe braln, whlch ls due Lo asLrocyLe prollferaLlon), Lhls ls analogous Lo flbroblasLs
laylng collagen Lype 3 ln Lhe wound.

u. nS wallarlan degeneraLlon ls Lhe mech of axonal regeneraLlon
ln nS, have Schwann cells, whlle ln Lhe CnS, have ollgodendrocyLes
(boLh make myelln). 1umor Schwann cell = schwannoma, lf lL lnvolves Cn vlll lL ls called
acousLlc neuroma. WhaL geneLlc dz LhaL ls auLo domlnanL has assoclaLlon?
neuroflbromaLous.

(Slde noLe: myasLhenla gravls Lensllon ln[ecLlon wlll lncrease Ach ln synapses ln eyellds,
and myasLhenlc crlsls wlll end)


V. Lxtra S|de notes and kev|ew of Inf|ammat|on:

A. LS8 puLLlng whole blood lnLo cyllnder and see when lL seLLles. 1he hlgher Lhe denslLy,
or welghL, Lherefore seLLle preLLy qulck and Lherefore have a lncrease sedlmenLaLlon raLe.
When sLuck LogeLher and looks llke colns = roulouex. When aggregaLed LogeLher =
lncreased sed raLe, whlch ls lncreased lgC and flbrlnogen (lncludes every acuLe and chronlc
lnflammaLlon Lhere ls. WhaL causes 88C lgM, b/c Lhe neg charge normally
88C lM cold aggluLlnlns are assoclaLed wlLh lgM
1 8
nose, ears, Loes, flngers Lurn blue). 1he lgM ab can cause cold aggluLlnlns, leadlng Lo
lschemla. AnoLher Lype of clumplng of lgM are Cryoglobullns l
lM P C M
lncreased e lC lM W
Macroglobemla).
35


8. AcuLe appendlclLls geL C8C, and wanL Lo see absoluLe neuLrophlllc leukocyLosls,
meanlng LhaL you have an lncrease of neuLrophlls ln Lhe perlpheral blood, also looklng for
Loxlc granulaLlon, and a LLl1 SPll1. Assumlng you sLarL from myeloblasL on Lhe lefL, and
evenLually form a segmenLed neuLrophll on Lhe rlghL, normally go lefL Lo rlghL on
maLuraLlon, Lherefore, wlLh a lefL shlfL, lLs means LhaL we go back Lo lmmaLure neuLrophlls,
Lhe deflnlLlons ls greaLer Lhan 10 band neuLrophlls ls consldered a LLl1 SPll1 (all Lhe
neuLrophlls are bands), lf you have [usL one meLamyelocyLe or one myelocyLe, lLs ls
auLomaLlcally consldered a LLl1 SPll1. ln acuLe appendlclLls, Lhere ls an absoluLe lncrease
ln neuLrophlls, wlLh Loxlc granulaLlon and a lefL shlfL.

C. MosL poLenL sysLem for kllllng bugs = C
2
dependenL myeloperoxldase sysLem,
Myeloperoxldase ls locaLed ln azurophlllc granules, whlch are lysosomes.
WanL a loL of lysosome ln an acuLe lnflammaLory rxn, b/c Lherefore Lhere ls more
myeloperoxldase around for kllllng bugs Lhls ls whaL Loxlc granulaLlon.
1herefore, Loxlc granulaLlon ensures LhaL Lhere ls enough myeloperoxldase Lo work LhaL
poLenL sysLem Lo klll bugs (C
2
dep myeloperoxldase sysLem).
CnA1Lk 3: ILUID AND nLMCDNAMICS

I. Ldema excess fluld ln Lhe lnLersLlLlal space, whlch ls exLracellular fluld (LCl), Lhls ls ouLslde
Lhe vessel

A. 1ypes of Ldema

1. non-lLLlng edema lncreased vessel permeablllLy wlLh pus ln Lhe lnLersLlal space
(pus=exudaLes). LymphaLlc fluld ls anoLher Lype of non-plLLlng edema. 8lockage of
lymphaLlcs leads Lo lymphaLlc fluld ln Lhe lnLersLlal space. lLs early, buL evenLually
becomes nonplLLlng. LxudaLes and lymphaLlc fluld does noL plL.

2. lLLlng edema LransudaLe wlLh rlghL hearL fallure, swelllng of Lhe lower exLremlLles,
fluld ln Lhe lnLersLlal space. 1ransudaLe does plL.

3. So Lhere are Lhree Lhlngs LhaL cause edema: exudaLes, lymphedema, and LransudaLe,
and LransudaLes are Lhe only one LhaL has plLLlng edema.

8. 1ransudate]|tt|ng Ldema
1ransudaLe deals wlLh sLarllng forces:

1. WhaL keeps fluld ln our blood vessels? Albumln, and Lhls ls called oncoLlc pressure.
80 of our oncoLlc pressure ls relaLed Lo Lhe serum albumln levels. AnyLlme Lhere ls
36

hypoalbumlnemla Lhen we wlll have a leaklng of a LransudaLe (proLeln of less Lhan 3
g/dL) leaklng lnLo lnLersLlal space vla caplllarles and venules (plLLlng edema),

2. normally, hydrosLaLlc pressure ls Lrylng Lo push fluld ouL. 1herefore, ln a normal
person, oncoLlc pressure ls wlnnlng. 1herefore, a decrease ln oncoLlc pressure and an
lncrease ln hydrosLaLlc pressure wlll lead Lo LransudaLe (plLLlng edema).

3. Albumln ls made ln Lhe llver. WlLh chronlc llver dz (clrrhosls), have a decreased
albumln level. Can you vomlL lL ouL? no. Can crap lL ouL (malabsorpLlon syndrome), or
can pee lL ouL (nephroLlc syndrome), can come off our skln (3
rd
degree burn b/c loslng
plasma), anoLher posslblllLy of low proLeln cL (low-lnLake) ls seen ln klds kwashlorkor
kld has faLLy llver and decreased proLeln lnLake, leadlng Lo low albumln level.

4. Lxamples:
a. erson wlLh Ml 24 hrs ago and he dled and he has fluld comlng ouL LransudaLe
b/c lncreased hydrosLaLlc pressure and lefL Pl due Lo Ml so Lhlngs backed up lnLo Lhe
lungs. 8/c Lhe CC decreased, Lhe Luv lncreases and pressure on lefL venLrlcle
lncreases, and Lhe pressure ls LransmlLLed lnLo Lhe lefL aLrlum, Lo Lhe pul veln, keeps
backlng up, and Lhe hydrosLaLlc pressure ln Lhe lung approaches Lhe oncoLlc
pressure, and a LransudaLe sLarLs leaklng lnLo Lhe lnLersLlLlal space, whlch leads Lo
acLlvaLlon of Lhe ! recepLor, whlch wlll cause dyspnea. Leads Lo full blown ln alveoll
and pulmonary edema, whlch ls whaL Lhls ls.

b. venom from bee sLlng on arm leads Lo exudaLe due Lo anaphylacLlc rxn (face
swelled), wlLh hlsLamlne belng Lhe propagaLor, and Lype one P?, causlng Llssue
swelllng. 8x alrway, 1:1000 aqueous eplnephrlne subcuLaneously

c. clrrhosls of llver, wlLh swelllng of Lhe legs: LransudaLe, mechanlsm: decreased
oncoLlc pressure b/c cannoL syn albumln, and lncreased hydrosLaLlc pressure b/c
porLal P1n, Lhere ls clrrhosls of Lhe llver, and Lhe porLal veln empLles lnLo Lhe llver, ln
Lhls case, lL cannoL, and Lhere ls an lncrease ln hydrosLaLlc pressure, pushlng Lhe fluld
ouL lnLo Lhe perlpheral cavlLles (so Lhere are 2 mech for aclLes). lLLlng edema ln
legs: decreased ln oncoLlc pressure

d. L wlLh dependenL plLLlng edema: pL has rlghL hearL fallure, and Lherefore an
lncrease ln hydrosLaLlc pressure, wlLh rlghL hearL fallure, Lhe blood behlnd Lhe falled
rlghL hearL ls ln Lhe venous sysLem, clrrhosls of llver ls due Lo decrease ln oncoLlc
pressure.

37

e. modlfled radlcal masLecLomy of LhaL breasL, wlLh nonplLLlng edema: lymphedema.
CLher causes w. bancrofLl, lymphogranulomon venarlum (subLype of chylamdla
LrachomaLa scarrlng Llssure and lymphaLlcs, leadlng Lo lymphedema of scroLum
l sL) deals
wlLh dermal lymphaLlcs plug wlLh Lumor, excess leads Lo dlmpllng, and looks llke Lhe
surface of an orange. MCC lymphedema = posLradlcal masLecLomy, can also run rlsk
of lymphanglosarcoma.

II. kena| hys|o

A. LCI]ICI
LCl (1/3) = exLracellular fluld of Lwo comparLmenLs vascular (1/3) and lnLersLlLlal (2/3)
lCl (2/3) = lnLracellular fluld comparLmenL

Lxample: how many llLers of lsoLonlc sallne do you have Lo lnfuse Lo geL 1 llLer lnLo Lhe
plasma? 3 LlLers (2/3:1/3 relaLlonshlp), 2 llLers ln lnLersLlal space, and 1 L would go Lo Lhe
vascular space, lL equlllbraLes wlLh lnLersLlal/vascular comparLmenLs.

8. Csmo|a||ty = measure of soluLes ln a fluld, due Lo Lhree Lhlngs: na, glucose, and blood
urea nlLrogen (8un) urea cycle ls locaLed ln Lhe llver, parLly ln Lhe cyLosol and parLly ln
Lhe mlLochondrla, usually mulLlply na Llmes 2 (b/c one na and one Cl).

Audlo flle 6: lluld and hemodyn 2
normal na ls 133-140 range, Llmes LhaL by 2 LhaL 280. lor glucose, normal ls 100 dlvlde
8un
llver, parL of Lhe cycle ls ln Lhe cyLosol and parL of lL ls ln mlLochondrla. 1he urea comes
8
cycle ls urea. 1he normal ls abouL 12, dlvlde LhaL by 3, so we have 4. 1herefore, ln a
normal person na ls conLrolllng Lhe plasma osmolallLy. 1o measure serum osmolallLy:
double Lhe serum na and add 10.

C. Csmos|s
2 of Lhese 3 are llmlLed Lo Lhe LCl comparLmenL, one can equlllbraLe beLween LCl and lCl
across Lhe cell membranes urea, Lherefore, wlLh an lncreased urea, lL can equlllbraLe
equally on boLh sldes Lo lL wlll be equal on boLh sldes, Lhls ls due Lo osmosls. 8/c na and
glucose are llmlLed Lo Lhe LCl comparLmenL, Lhen changes ln lLs concenLraLlon wlll resulL ln
Lhe movemenL of WA1L8 from low Lo hlgh concenLraLlon (opposlLe of dlffuslon le ln
lungs, 100 mmPg ln alveoll of C
2
, and reLurnlng from Lhe Llssue ls 40 mmPg pC
2
, 100 vs. 40,
whlch ls blgger, 100 ls blgger, so vla dlffuslon, C
2
moves Lhrough Lhe lnLerspace lnLo Lhe
38

plasma Lo lncrease C
2
Lo abouL 93mmPb). 1herefore, ln dlffuslon, lL goes from hlgh Lo low,
whlle ln osmosls, lL goes from low Lo hlgh concenLraLlon.

1. Lxample: ln Lhe case wlLh hyponaLremla waLer goes from LCl lnLo Lhe lCl, b/c Lhe
lower parL ls ln Lhe LCl (hence P?CnaLremla), waLer goes lnLo Lhe lCl, and Lherefore ls
expanded by osmosls. now make belleve LhaL Lhe braln ls a slngle cell, whaL wlll we
see? cerebral edema and menLal sLaLus abnormallLles vla law of osmosls (Lhe
lnLracellular comparLmenL of all Lhe cells ln Lhe braln would be expanded)

2. Lxample: hypernaLremla waLer goes ouL of Lhe lCl lnLo Lhe LCl, Lherefore Lhe lCl
wlll be conLracLed. So ln Lhe braln, lL wlll lead Lo conLracLed cells, Lherefore menLal
sLaLus abnormallLles, Lherefore, wlLh hypo and hypernaLremla, wlll geL menLal sLaLus
abnormallLles of Lhe braln.

3. Lxample: ukA have (1000mg) large amounL blood sugar. 8emember LhaL boLh na
and glucose are llmlLed Lo Lhe LCl comparLmenL. ?ou would Lhlnk LhaL glucose ls ln Lhe
lCl ?
Lhe lCl (agaln lLs noL) b/c Lo order Lo geL lnLo Lhe cell (lnLracellular), glucose musL blnd
Lo phosphorus, generaLlng C6
galacLose, whlch are also meLabollzed lmmedlaLely, Lherefore, Lhere ls no glucose,
frucLose, or galacLose, per se, lnLracellularly). So, wlLh hyperglycemla, Lhere ls hlgh
glucose ln Lhe LCl, so waLer wlll move from lCl Lo LCl. 1herefore, Lhe serum na
concenLraLlon wlll go down Lhls ls called dlluLlonal hyponaLremla (whlch ls whaL
happens Lo Lhe serum sodlum wlLh hyperglycemla).
1herefore Lhe Lwo Lhlngs LhaL conLrol waLer ln Lhe LCl are na and glucose, buL a normal
slLuaLlon, na conLrols. urea does noL conLrol waLer movemenLs b/c lLs permeable, and can
geL Lhrough boLh comparLmenLs Lo have equal concenLraLlons on boLh sldes.

D. 1on|c|ty lsoLonlc sLaLe, hypoLonlc sLaLe, and hyperLonlc sLaLe
We have all dlfferenL Lypes of sallne: lsoLonlc sallne, hypoLonlc sallne (1/2 normal sallne, x
normal sallne, 3 dexLrose ln waLer), and hyperLonlc sallne (3, 3), normal sallne ls 0.9.
We are referrlng Lo normal LonlclLy of Lhe plasma, whlch ls conLrolled by Lhe serum na.
1hese are Lhe Lhree Lypes of LonlclLy (lso, hypo, and hyper). Serum na ls a reflecLlon of
LoLal body na dlvlded by LoLal body P
2
0. lor example: hypernaLremla ls noL [usL caused by
lncreased LoLal body na, lL can also be caused by decreaslng LoLal body waLer wlLh a normal
LoLal body na, Lherefore Lhere ls an lncrease ln serum na concenLraLlon. lL ls really a raLlo
of LoLal body na Lo LoLal body P
2
0. 1o deLermlne serum na, [usL look aL serum levels. WlLh
dlfferenL fluld abnormallLles, can lose or galn a cerLaln LonlclLy of fluld.

39

1. Isoton|c |oss of f|u|d look aL raLlo of LoLal body na and waLer, ln Lhls case, you are
loslng equal amounLs of waLer and na, hence lSCLonlc. 1hls fluld ls malnly losL from Lhe
LCl. 1he serum na concenLraLlon ls normal when loslng lsoLonlc fluld. LCl would look
conLracLed. 1here would be no osmoLlc gradlenL movlng lnLo or ouL of Lhe LCl. Cllnlcal
condlLlons where Lhere ls an lsoLonlc loss of fluld: hemorrhage, dlarrhea.

lf we have an |soton|c ga|n, we have ln equal lncrease ln salL and waLer, le someone
geLLlng Loo much lsoLonlc sallne, normal serum na, excess lsoLonlc na would be ln Lhe
LCl, and Lhere would be no osmoLlc gradlenL for waLer movemenL.

2. nypoton|c so|ut|ons by deflnlLlon, lL means hyponaLremla. Pypoglycemla wlll noL
produce a hypoLonlc condlLlon. MCC of low osmolallLy ln plasma ls hyponaLremla.
Pow? Lose more salL Lhan waLer, Lherefore, serum na would be decreased. lf loslng
more salL Lhan waLer, kldney ls probably Lhe locaLlon of where/why lL ls happenlng.
Maln place Lo deal wlLh sodlum (elLher Lo geL rld of lL or Lo geL lL back) ls ln kldney, esp
when deallng wlLh dlureLlcs (furosemldes and PC1Z). 1he LonlclLy of soluLlon you lose ln
you P?L8
condlLlon. LCl concenLraLlon ls low wlLh hyponaLremla, Lherefore Lhe waLer wlll move
lnLo Lhe lCl comparLmenL. (Csmosls-remember low Lo hlgh)

Lxample: lf you galned pure waLer, and no salL, you have really lowered your serum
na: MCC = SlAuP ln small cell carclnoma of Lhe lung, you galn pure waLer b/c AuP
renders Lhe dlsLal and Lhe collecLlng Lubule permeable Lo free waLer. WlLh AuP
presenL, wlll be reabsorblng waLer back lnLo Lhe LCl comparLmenL, dlluLlng Lhe
serum na, and Lhe LCl and lCl wlll be expanded. 1he LCl ls expanded due Lo waLer
reabsorpLlon, and Lhe lCl ls expanded b/c lL has a hlgh concenLraLlon levels (lLs levels
are noL dlluLed). 1hls can lead Lo menLal sLaLus abnormallLles. 1herefore, Lhe more
waLer you drlnk, Lhe lower your serum na levels would be. 1he LreaLmenL ls by
u n n W AuP
ls presenL, you wlll CCnCLn18A1L your urlne b/c Laklng free waLer ouL of urlne, wlLh
absenL AuP, lose free waLer and Lhe urlne ls dlluLed. 1herefore, for wlLh SlAuP,
waLer sLays ln Lhe body, goes lnLo Lhe LCl comparLmenL, and Lhen move lnLo Lhe lCl
comparLmenL vla osmosls. 1he lowesL serum sodlum wlll be ln SlAuP. Cn Lhe
boards, when serum na ls less Lhan 120, Lhe answer ls always SlAuP. Lxample: pL
wlLh SlAuP, noL a smoker (Lherefore noL a small cell carclnoma), Lherefore, look aL
drugs she was on chlorpropramlde, oral sulfylureas produce SlAuP.

Lxample: Caln boLh waLer and salL, buL more waLer Lhan salL, leadlng Lo
hyponaLremla Lhese are Lhe plLLlng edema sLaLes le 8Pl, clrrhosls of Lhe llver.
When LoLal body na ls lncreased, lL always produces plLLlng edema. WhaL
40

comparLmenL ls Lhe LoLal body na ln? LCl WhaL ls Lhe blggesL LCl comparLmenL?
lnLersLlal comparLmenL. 1herefore, lncrease ln LoLal body na wlll lead Lo expanslon
of lnLersLlal comparLmenL of Lhe LCl, waLer wlll follow Lhe na, Lherefore you geL
expanslon vla LransudaLe and plLLlng edema, seen ln rlghL Pl and clrrhosls.

Lxample: hyperLonlc loss of salL (from dlureLlc) leads Lo hyponaLremla

Lxample: SlAuP (galnlng a loL of waLer) leads Lo hyponaLremla

Lxample: galnlng more waLer Lhan salL wlll lead Lo hyponaLremla: plLLlng edema

3. nyperton|c state by deflnlLlon, have Loo much na (hypernaLremla) or have
hyperglycemla (le pL wlLh ukA has a hyperLonlc condlLlon, whlch ls more common Lhan
hypernaLremla). WlLh hypernaLremla, whaL does lCl look llke? lL wlll always be
conLracLed or shrunken.
rlmary aldosLeronslm galn more salL and waLer.

ulabeLes lnslpldus Lose pure waLer (vs. galnlng pure salL ln SlAuP). lf you lose more
waLer Lhan salL ln Lhe urlne, you have osmoLlc dluresls mlxLure. When Lhere ls glucose
and mannlLo

Lxample: 8aby dlarrhea = hypoLonlc salL soluLlon (adulL dlarrhea ls lsoLonlc), Lherefore,
lf baby has no access Lo waLer and has a roLavlrus lnfecLlon, serum sodlum should be
hlgh because loslng more waLer Lhan salL, leadlng Lo hypernaLremla. Powever, mosL
moms glve Lhe baby waLer Lo correcL Lhe dlarrhea, Lherefore Lhe baby wlll come ln wlLh
normal serum na or even hyponaLremla b/c Lhe denomlnaLor (P
2
C) ls lncreased.
1reaLmenL ls pedlalyLe and CaLorade Lhese are hypoLonlc salL soluLlon ([usL glve Lhem
back whaL Lhey losL). WhaL has Lo be ln pedlalyLe and whaL has Lo be ln CaLorade Lo
order Lo reabsorb Lhe na ln Lhe Cl LracL? Clucose b/c of Lhe co-LransporL. WlLh Lhe co-
LransporL, Lhe na PAS Lo be reabsorbed wlLh glucose or galacLose. Lxample: cholera, ln
oral replacemenL, need glucose Lo reabsorb na b/c co-LransporL pump locaLed ln Lhe
small lnLesLlne. CaLorade has glucose and sucrose (whlch ls converLed Lo frucLose and
glucose).

SweaL = hypoLonlc salL soluLlon, lf you are sweaLlng ln a maraLhon, you wlll have
hypernaLremla

L. Vo|ume Compartments
ArLerlal blood volume ls same as sLroke volume and CC (cardlac ouLpuL). When CC
decreases, all physlologlc processes occur Lo resLore volume. WlLh decrease CC (le
41

hypovolemla), oxygenaLed blood wlll noL geL Lo Llssues, and we can dle. 1herefore,
volume ls essenLlal Lo our bodles.

We have barorecepLors (low and hlgh pressure ones). 1he low pressure ones are on Lhe
venous slde, whlle Lhe hlgh pressure ones are on Lhe arLerlal slde (le Lhe caroLlds and
arch of aorLa). 1hey are usually lnnervaLed by Cn 9 and 10 (Lhe hlgh pressure ones).
When Lhere ls a decrease ln arLerlal blood volume (decreased Sv or CC), lL wlll under flll
Lhe arch vessels and Lhe caroLld, lnsLead of 9
Lh
or 10
Lh
nerve response, you have a
sympaLheLlc nS response, Lherefore caLecholamlnes are released. 1hls ls good b/c Lhey
wlll consLrlcL Lhe venous sysLem, whlch wlll lncrease blood reLurnlng Lo Lhe rlghL slde of
Lhe hearL (do noL wanL venodllaLlon b/c lL wlll pool ln your legs). CaLecholamlnes wlll
acL on Lhe beLa adrenerglc recepLors on Lhe hearL, whlch wlll lncrease Lhe force of
conLracLlon, Lhere wlll be an lncrease ln sLroke volume (sllghL) and lL wlll lncrease hearL
8 A
sysLemlc slde: sLlmulaLe beLa recepLors ln smooLh muscle. ulasLollc pressure ls really
due Lo Lhe amounL of blood ln Lhe arLerlal sysLem, whlle you hearL ls fllllng wlLh blood.
Who conLrols Lhe amounL of blood ln arLerlole sysLem, whlle your hearL ls fllllng ln
dlasLole? ?our perlpheral reslsLance arLerloles LhaL malnLalns your dlasLollc blood
pressure. So, when Lhey are consLrlcLed, very llLLle blood ls golng Lo Lhe Llssues (bad
news), good news: keep up dlasLollc pressure Lhls ls lmporLanL b/c Lhe coronary
arLerles flll ln dlasLoles. 1hls ls all done wlLh caLecholamlnes. 8enln sysLem ls acLlvaLed
by caLecholamlnes, Loo, angloLensln ll can vasoconsLrlcLor Lhe perlpheral arLerloles
(Lherefore lL helps Lhe caLecholamlnes). AC ll sLlmulaLes 18 hydroxylase, whlch converLs
corLlcosLerone lnLo aldosLerone, and sLlmulaLes aldosLerone release, whlch leads Lo
reabsorpLlon of salL and waLer Lo geL cardlac ouLpuL up.
WlLh decreased Sv, renal blood flow Lo Lhe kldney ls decreased, and Lhe 8AA can be
sLlmulaLed by Lhls mechanlsm, Loo. Where exacLly are Lhe recepLors for Lhe
[uxLaglomerlur apparaLus? AfferenL arLerlole. 1here are sensors, whlch are modlfled
smooLh muscle cells LhaL sense blood flow. AuP wlll be released from a nerve response,
and pure waLer wlll lncrease buL LhaL does noL help wlLh lncreaslng Lhe cardlac ouLpuL.
need salL Lo lncrease CC.

Lxample L ld how can you keep 8
up? Clve normal sallne ls lsoLonlc Lherefore Lhe sallne wlll sLay ln Lhe LCl comparLmenL.
normal sallne ls plasma wlLhouL Lhe proLeln. Any Llme you have hypovolemlc shock,
glve normal sallne Lo lncrease 8 b/c lL sLays ln Lhe LCl comparLmenL. CannoL ralse 8
wlLh x normal sallne or 3 dexLrose, have Lo glve someLhlng LhaL resembles plasma and
has Lhe same LonlclLy of plasma. normal sallne ls 0.9.

42

erlLubular caplllary pressures: you reabsorb mosL of Lhe sodlum ln Lhe proxlmal Lubule
(60-80). Where ls Lhe resL absorbed?, ln Lhe dlsLal and collecLlng Lubule by
aldosLerone. 1he na ls reabsorbed lnLo Lhe perlLubular caplllarles. SLarllng forces ln Lhe
caplllarles musL be amenable Lo lL. 1wo sLarllng forces: oncoLlc pressure (keeps flulds ln
Lhe vessel) and hydrosLaLlc (pushes flulds ouL of vessel).

Lxample: When renal blood flow ls decreased (wlLh a decreased Sv and CC), whaL
happens Lo Lhe perlLubular caplllary hydrosLaLlc pressure? lL decreases. 1herefore, Lhe
perlLubular oncoLlc pressure ls lncreaslng (le Lhe force LhaL keeps flulds ln Lhe vessel),
and LhaL ls responslble for reabsorpLlon of anyLhlng lnLo Lhe blood sLream from Lhe
kldney. 1hls ls why C (perlLubular oncoLlc pressure) > P (hydrosLaLlc pressure of
perlLubular caplllary), allows absorpLlon of salL conLalnlng fluld back lnLo blood sLream
lnLo Lhe kldney.

1onlclLy of fluld reabsorblng ouL of proxlmal Lubule ls lsoLonlc (llke glvlng normal sallne).
AuP ls reabsorblng lsoLonlc salL soluLlon, buL noL as much as Lhe proxlmal Lubule. AuP

add Lhe AuP effecL and Lhe pL becomes sllghLly hyponaLremlc and hypoLonlc, Lherefore
absorbs lnLo Lhe LCl comparLmenL when Lhere ls a decreased CC.

CpposlLe Lxample: lncreased Sv, and lncrease arLerlal volume, wlll lead Lo sLreLch of
barorecepLors (lnnervaLed by 9
Lh
and 10
Lh
nerve), and a parasympaLheLlc response wlll
be ellclLed, lnsLead of a sympaLheLlc response. 1here wlll noL be any venuloconsLrlcLlon
nor any lncrease ln Lhe force of conLracLlon of Lhe hearL. 1hls ls fluld overload,
Lherefore we need Lo geL rld of all Lhe volume. 1here ls lncreased renal blood flow, so
Lhe 8AA wlll noL be acLlvaLed. lluld overload does noL AuP be released. 1he
perlLubular hydrosLaLlc pressure ls greaLer Lhan Lhe oncoLlc. Lven of Lhe pL absorbed
1
loslng hypoLonlc salL soluLlon wlLh lncreased ln arLerlal blood volume.

need Lo know whaL happens lf Lhere ls decreased CC, whaL happens when An ls
released from Lhe aLrla, and glve off dlureLlc effecL, lL wanLs Lo geL rld salL. An ls only
released ln volume overloaded sLaLes.

Lxample: pL glven 3 hyperLonlc sallne: whaL wlll happen Lo osmolallLy? lncrease.
WhaL wlll LhaL do Lo serum AuP? lncrease lncrease of osmolallLy causes a release of
AuP.
Lxample: WhaL happens ln a pL wlLh SlAuP? decreased plasma osmolallLy, hlgh AuP
levels.
43

Lxample: WhaL happens ln a pL wlLh ul? no AuP, Lherefore, serum na lncreases, and
AuP ls low

Pow Lo Lell LoLal body na ln Lhe pL: 1wo plcs: pL wlLh dry Longue = Lhere ls a decrease
ln LoLal body na, and Lhe pL wlLh lndenLaLlon of Lhe skln, Lhere ls an lncrease ln LoLal
body na. uehydraLlon: Skln Lurgur ls preformed by plnchlng Lhe skln, and when Lhe skln
goes down, Lhls Lells you LhaL LoLal body na ls normal ln lnLersLlal space. Also look ln
mouLh and aL mucous membranes.

lf you have dependenL plLLlng edema LhaL means LhaL Lhere ls an lncrease ln LoLal body
na.

SlAuP galnlng pure waLer, LoLal body sodlum ls normal, buL serum na ls low, have Lo
resLrlcL waLer.

8lghL Pl and dependenL plLLlng edema fluld kldney reabsorbs ls hypoLonlc salL
soluLlon wlLh a decreased CC (llLLle more waLer Lhan salL), Lherefore serum na wlll low.
numeraLor ls lncreased for LoLal body sodlum, buL denomlnaLor has larger lncrease wlLh
waLer.

WhaL ls nonpharmaloglcal 8x of any edema sLaLes? (le 8Pl/llver dz) resLrlcL salL and
waLer

WhaL ls Lhe 8x for SlAuP = resLrlcL P
2
C

WhaL ls Lhe 8x for any plLLlng edema sLaLe? 8esLrlcL salL and waLer
harmacologlcal 8x for plLLlng waLer dlureLlcs (also geL rld of some salL).

III. Shock

A. Causes of hypovo|em|c shock dlarrhea, blood loss, cholera, sweaLlng, noL ul (b/c loslng
pure waLer, and noL loslng na, LoLal body na ls nC8MAL! Loslng waLer from lCl, no slgns of
dehydraLlon, when you lose salL, show slgns of dehydraLlon).

Lxample: lady wlLh hypovolemlc shock when she was lylng down, her 8 and pulse
were normal, when Lhey saL her up, Lhe 8 decreased and pulse wenL up. WhaL does
Lhls lndlcaLe? 1haL she ls volume depleLed. 1hls ls called Lhe 1lL1 LesL. normal 8 when
lylng down b/c Lhere ls no effecLlve gravlLy, Lherefore normal blood reLurnlng Lo Lhe
rlghL slde of Lhe hearL, and normal CC. Powever, when you slL Lhe paLlenL up, and
44

lmpose gravlLy, you decrease Lhe venous reLurn Lo rlghL hearL. So, lf you are
hypovolemlc, lL wlll show up by a decrease ln 8 and an lncrease ln pulse.
Cardlac ouLpuL ls decreased, and Lhe caLecholamlne effecL causes Lhls scenarlo. Pow
would you 8x? normal sallne.

Audlo flle 7: lluld and hemodyn 3
Lxample: pL collapses, and you do a LllL LesL: 100/80 and pulse of 120 whlle lylng down.
SlLLlng up, lL was 70/60 and pulse of 130. 1he pL ls severely hypovolemlc, Lherefore 8x ls
normal sallne. 1reaLmenL: Cne llLer ln, showed no slgns, puL anoLher llLer and Lhe 8
becomes normal, and ls feellng beLLer, buL sLlll slgns of volume depleLlon (dry mouLh).
We have Lhe 8 sLablllzed, buL Lhe pL losL hypoLonlc salL soluLlon, Lherefore we need Lo
S lv
W 1
glve x normal sallne. 1he LreaLmenL proLocol ls: when a pL loses someLhlng, you replace
whaL Lhey losL. And when pL ls hypovolemlc, always glve lsoLonlc sallne.

Lxample: ukA, have osmoLlc dluresls, LonlclLy of fluld ln Lhe urlne LhaL has excess
glucose ls hypoLonlc. PypoLonlc fluld has a llLLle more fluld Lhan salL. So Lhe pL ls
severely hypovolemlc, Lherefore Lhe flrsL sLep ln managemenL ls correcLlon of volume
depleLlon. Some people are ln hypovolemlc shock from all LhaL salL and waLer loss.
1herefore need Lo correcL hypovolemla and Lhen correcL Lhe blood sugar levels (ukA pLs
lose hypoLonlc soluLlon). 1herefore, flrsL sLep for ukA pL ls Lo glve normal sallne b/c you
wanL Lo make Lhem normo- u
unless you correcL Lhe hypovolemla. lL can Lake 6-8 llLers of lsoLonlc sallne before Lhe
blood pressure sLarLs Lo sLablllze. AfLer pL ls feellng beLLer and Lhe pL ls flne volume
wlse. now whaL are we golng Lo do? 1he pL ls sLlll loslng more waLer Lhan salL ln urlne,
Lherefore sLlll loslng a hypoLonlc salL soluLlon, Lherefore need Lo hang up an lv wlLh x
normal sallne (le Lhe raLlo of soluLes Lo waLer) and lnsulln (b/c Lhe pL ls looslng glucose).

So, flrsL Lhlng Lo do always ln a pL wlLh hypovolemlc shock ls normal sallne, Lo geL Lhe 8
normal. 1hen Lo correcL Lhe problem LhaL caused Lhe hypovolemla. lL depends on whaL
ls causlng Lhe hypovolemla (le lf pL ls sweaLlng, glve hypoLonlc salL soluLlon, lf dlarrhea
sallne), lf pL wlLh ul (le sLable 8, pL ls lucld)
glve waLer (Lhey are loslng waLer, Lherefore glve 3 dexLrose (le 30 glucose) and
waLer).

8. Iour k|nds of shock:
1. Pypovolemlc shock: blood loss, dlarrhea (adulL or chlld), baslcally whenever you are
lose salL, you could end up wlLh hypovolemlc shock
2. Cardlogenlc shock: MC due Lo Ml
45

3. neurogenlc shock: assoc. wlLh splnal cord ln[urles
4. SepLlc shock: MC due Lo L. coll, also MCC sepsls ln hosplLal and ls due Lo an lndwelllng
of Lhe urlnary caLheLer. SLaph aureus ls noL Lhe MC cause of lv relaLed sepLlcemla ln Lhe
hosplLal, L.Coll wlns hands down. LndoLoxln ln cell wall ls a llpopolysacharlde, whlch are
seen ln gram negaLlve bacLerla. 1he llplds are endoLoxlns. 1herefore, gram negaLlves
have llplds (endoLoxlns) ln Lhelr cell wall, gram poslLlve do noL. SC lf you have L.Coll
sepsls, you wlll have blg Llme problems, and ls called sepLlc shock.

3. Classlcal cllnlcal presenLaLlons:

a) Pypovolemlc and cardlogenlc shock: you would see cold and clammy skln, b/c of
vasoconsLrlcLlon of Lhe perlpheral vessels by caLecholamlnes (release ls due Lo Lhe
decrease ln Sv and CC) and AC ll. 1hese wlll vasoconsLrlcL Lhe skln and redlrecL Lhe
blood flow Lo oLher lmporLanL organs ln Lhe body llke braln and kldneys, leadlng Lo a
cold clammy skln. 8 ls decreased, pulse ls lncreased.

b) : ls a concepL LhaL Leaches you abouL perlpheral reslsLance of
arLerloles whlch conLrol Lhe dlasLollc blood pressure.

18 = 1oLal perlpheral reslsLance of Lhe arLerloles
v = vlscoslLy
r = radlus of Lhe vessel Lo Lhe 4
Lh
power

1he maln facLor conLrolllng 18 ls radlus Lo Lhe 4
Lh
power
WhaL conLrols Lhe vlscoslLy ln Lhe blood? Pb. So lf you are anemlc, vlscoslLy of blood
ls decreased (le low hemoglobln), and lf you have polycyLhemla (hlgh hemoglobln),
vlscoslLy wlll be lncreased. 1herefore, 18 ln anemla wlll decrease, and ln
polycyLhemla wlll lncrease.

c) SepLlc shock 1here ls a release of endoLoxlns whlch acLlvaLes Lhe alLernaLlve
complemenL sysLem. 1he complemenL wlll evenLually release C3a and C3a whlch are
anaphylaLoxlns, whlch wlll sLlmulaLe Lhe masL cells Lo release hlsLamlne. 1he
hlsLamlne causes vasodllaLlon of arLerloles (Lhe same ones of Lhe perlpheral
reslsLance arLerloles). 1herefore blood flow ls lncreased LhroughouL Lhe perlpheral
reslsLance arLerloles and Lhe skln feels warm. 1he endoLoxlns also damage Lhe
endoLhellal cells, as a resulL, Lwo poLenL vasodllaLors (nC and Cl
2
) are released.
1herefore, 2 or 3 vasodllaLors are released, and affecL Lhe 18 Lo Lhe fourLh power.
1herefore, Lhe 18 wlll decrease (due Lo vasodllaLlon).

TPR = V/r
4


46

18 arLerloles conLrol your dlasLollc 8 b/c when Lhey are consLrlcLed, Lhey conLrol
Lhe amounL of blood LhaL remalns ln Lhe arLerlal sysLem whlle your hearL ls fllllng up
ln dlasLole. 1herefore, when Lhe 18 arLerloles are dllaLed, Lhe dlasLollc 8 wlll pan
ouL.
1hlnk of a dam (wlLh gaLes): lf all Lhe gaLes are wlde open all LhaL waLer wlll come
gushlng Lhrough. 1hls ls whaL happens Lo Lhe arLerloles when Lhey are dllaLed. 1he
blood gushes ouL and goes Lo Lhe caplllary Llssues, supposedly feedlng all Lhe Llssues
wlLh C
2
. 1hlnk ln Lhe conLexL of flshlng: when Lhe dam wall opens, all Lhe waLer
rushes Lhru causlng LurbulenL waLers, Lherefore Lhls would be a bad Llme Lo go
flshlng. 1he flshes would be Lrylng Lo save Lhemselves. 1haL ls whaL Lhe C
2
ls dolng.
1herefore, wlLh all Lhls blood golng by, Lhe Llssues cannoL exLracL C
2
b/c lL ls golng
1 od ls comlng
back Lo Lhe rlghL slde of Lhe hearL fasLer Lhan usual, b/c all Lhe arLerloles are wldely
dllaLed. uue Lo Lhe blood golng back Lo Lhe hearL fasLer, Lhe cardlac ouLpuL ls
lncreased. 1hls ls seen ln sepLlc shock and Lhe skln feels warm b/c Lhe vessels are
dllaLed. 1herefore, wlLh sepLlc shock, Lhere ls a PlCP ouLpuL fallure, wlLh warm skln.

Powever, ln hypovolemlc and cardlogenlc shock, Lhe cardlac ouLpuL ls decreased (b/c
Lhe vessels are consLrlcLed by caLecholamlnes and angloLensln ll), and Lhe skln feels
cold and clammy.

C. Swan ganz catheter ls lnserLed ln Lhe rlghL slde of Lhe hearL and lL measures all
parameLer LhaL ls LaughL ln physlology. All of Lhese Lhlngs are measured ln a swan ganz
caLheLer.
1. Cardlac CuLpuL: measured by swan ganz

2. SysLemlc vascular reslsLance: Lhls ls a calculaLlon. 1he baslcally measures Lhe 18, le
measures whaL arLerloles are dolng

3. Mlxed venous C
2
conLenL. ?ou know normally LhaL Lhe C
2
conLenL ls equal Lo = 1.34 x
Pb x C
2
C
2
. Measured ln 8A wlLh swan ganz caLheLer, Lhls ls Lhe 8LS1 1LS1 for
evaluaLlng Llssue hypoxla.

Cardlac ouLpuL ln cardlogenlc and hypovolemlc shock ls low, Lherefore, blood noL belng
pushed ahead wlLh a greaL deal of force. So, Llssue wlll have a loL of Llme Lo exLracL C
2

from whaL llLLle blood LhaL ls belng dellvered. As a resulL, mlxed venous C
2
conLenL ln
hypovolemlc and cardlogenlc shock wlll be decreased le very low b/c Lhe blood golng
Lhrough Lhe vessels ls very slow (no force ls helplng Lo push lL Lhrough). 1herefore, lL
exLracLs more C
2
Lhan normal. Mlxed venous C
2
conLenL ln sepLlc shock (when blood ls
47

passlng Lhrough vessels aL a very fasL raLe) wlll lead Lo a PlCP mlxed venous conLenL
(b/c Llssues unable Lo exLracL C
2
).

4. ulmonary caplllary wedge pressure measures LefL venLrlcular end dlasLollc volume
and pressure (Luv and Lu). CaLheLer ln rlghL hearL wlll Lell you whaL Lhe pressure ls ln
Lhe lefL venLrlcle.

3. ulfferences beLween Pypovolemlc, Cardlogenlc, and SepLlc Shock uslng swan ganz
caLheLer:

CC ln hypovolemlc and cardlogenlc? boLh decreased
CC ln sepLlc shock? lncreased

SysLemlc vasc reslsLance (18) ls a measure of whaL Lhe A81L8lCLLS are dolng.
WhaL ls 18 ln hypovolemlc and cardlogenlc shock? lncreased due Lo
vasoconsLrlcLlon
18 ln sepLlc shock? uecreased due Lo vasodllaLlon.

Mlxed venous ln hypovolemlc and cardlogenlc? Low.
Mlxed venous ln sepLlc shock? Plgh.

Pow do we separaLe hypovolemlc and cardlogenlc?
ulmonary caplllary wedge pressure (measures lefL venLrlcular Luv)
ln Pypovolemlc, whaL ls LvLuv? Low.
ln Cardlogenlc, whaL ls LvLuv? Plgh.
l L

D. Lxamp|es:

1. Lxample: Cf all organs ln Lhe body, whlch suffers Lhe greaLesL due Lo decreased 8?
kldneys. WhaL parL? Medulla. noL Lhe braln b/c wlLh decreased CC, Lhe clrcle of wlllls
wlll dlsLrlbuLe blood flow Lo cerLaln areas ln Lhe braln, especlally Lhe areas where Lhere
are neurons. Someone wlLh hypovolemlc, or cardlogenlc, or sepLlc shock: ollgurla, and
an lncreased ln 8un/CreaLlne causes sugars ln Lhe body. 1hls occurs b/c Lhe paLlenL ls
golng lnLo acuLe Lubular necrosls. nephrologlsLs wanL Lo correcL Lhe renal blood flow,
so LhaL you can prevenL A1n b/c a pL can dle. WhaL Lype of necrosls? CoagulaLlon
necrosls. 1he dead renal Lubules wlll slough off and produce renal Lubular casLs ln Lhe
urlne whlch wlll block urlne flow, Lhereby produclng ollgurla. 1here ls also a decrease ln
Cl8, leadlng Lo A1n (chances of survlval are zero). So lL ls Lhe kldneys LhaL are Lhe mosL
48

affecLed when Lhe cardlac ouLpuL ls decreased, le decreased blood flow. 8raln would be
a close second Lo necrosls. 1he hearL has a blL of a collaLeral clrculaLlon as well.

2. Lxample C
2

Lenslon ls low enough Lo lnduce slckllng. 1herefore lf you have a young black woman
wlLh mlcroscoplc hemaLurla comlng Lo Lhe offlce, whaL ls flrsL LesL you should do? Slckle
cell screen, b/c she probably has Lhe slckle cell LralL. 1herefore, slckle cell LralL has
problems, b/c C
2
Lenslon ln renal medulla ls low enough Lo lnduce slckllng ln perlLubular
1
produce CoagulaLlon necrosls (aka A1n)

IV. Ac|d-base and 8|ood Gas
Acldosls lncrease ln P
+
lons, Lherefore decrease ln pP
Alkalosls decrease ln P
+
lons, Lherefore lncrease ln pP

A. New equat|on for acld/base physlo by Col[an:




8. Compensat|on = bodles aLLempL Lo Lry Lo malnLaln a normal pP (whlch lL never does). So
lf you wanL Lo keep pP roughly normal (assumlng you could).

1. Lxample: lf you have meLabollc alkalosls (lncrease ln blcarb: whlch ls ln Lhe
numeraLor), Lhen have Lo lncrease denomlnaLor (pCC
2
) Lo keep lL normal, Lherefore,
compensaLlon ls due Lo resplraLory (pCC
2
) acldosls. A nlce way of memorlzlng lL ls whaL
ls Lhe opposlLe of meLabollc? 8esplraLory and whaL ls Lhe opposlLe of acldosls? Alkalosls,
and vlce versa.

2. Lxample: lf you have meLabollc acldosls (decrease blcarb) whaL do we have Lo do
wlLh Lhe pCC
2
? We have Lo geL rld of lL. lf we decrease Lhe nomlnaLor, we have Lo
decrease Lhe domlnaLor ln order for Lhe equaLlon Lo sLay Lhe same. 1herefore, we have
Lo blow off Lhe CC
2
(hypervenLllaLlon).

3. venLllaLlon ls a CC
2
Lerm!
PypervenLllaLlon = lncrease ln resplraLory raLe allows for Lhe blowlng off of CC
2
,
Lherefore resulLs ln resplraLory alkalosls. lor Lhe LreaLmenL of resplraLory alkalosls ls Lo
pH = [HCO
3
-
] / pCO
2


Increase in bicarb = increase pH = metabolic alkalosis
Decrease in bicarb = decrease pH = metabolic acidosis

Increase pCO
2
= decrease pH = respiratory acidosis
Decrease pCO
2
= increase pH = respiratory alkalosis

49

glve Lhe pL a paper bag and ask Lo breaLh ln lL, b/c Lhen Lhey are re-breaLhlng Lhelr own
CC
2
.

PypovenLllaLlon = uecrease ln resplraLory raLe allows for Lhe reLenLlon of CC
2
, Lherefore
resulLs ln resplraLory acldosls.

lull compensaLlon does noL exlsL, you never brlng back Lhe pP Lo Lhe normal range. 1here
ls one excepLlon: chronlc resplraLory alkalosls ln hlgh alLlLude, le mounLaln slckness (le
peru).

C. kesp|ratory cond|t|ons: ac|dos|s and a|ka|os|s
1. 1hlngs LhaL deal wlLh CC
2
:

a) 8esplraLory cenLer ls ln medulla oblongaLa, whlch conLrols Lhe breaLhlng raLe

b) upper alrways lf obsLrucLed, Lhere wlll be a problem geLLlng rld of CC
2
.
c) ChesL bellows mosL lmp muscle of resplraLlon ls dlaphragm. Cn lnsplraLlon: Lhe
dlaphragm goes down, Lhe negaLlve lnLraLhroaclc pressure lncreases, and alr ls
sucked lnLo Lhe lungs and blood ls sucked lnLo Lhe rlghL slde of Lhe hearL (Lhls ls why
neck velns collapse on lnsplraLlon). negaLlve vacuum sucks blood and alr lnLo your
C l
Lhe lefL hearL Lo push blood ouL and lL also helps Lhe lungs by pushlng ouL alr.

2. Lxamples:
(a) 8arblLuraLes or any drug LhaL depresses Lhe resplraLory cenLer wlll leads Lo
resplraLory acldosls

(b) CnS ln[ury Lo medulla oblongaLa resp acldosls

(c) AnxleLy = MCC resp alkalosls. When you Lake a LesL, someLlmes you feel sLrange,
and geL numb and Llngly, especlally around mouLh and on Lhe Llps of flngers, and
become LwlLchy (b/c you are ln LeLany) lLs all caused by belng alkaloLlc and lonlzlng
calclum level geLs lower and you really are geLLlng LeLany. 1herefore you become

LeLany). All due Lo LeLany b/c of breaLhlng Loo fasL from anxleLy.

(d) regnanL woman have resp alkalosls b/c esLrogen and progesLerone over
sLlmulaLe Lhe resplraLory cenLer. LocaLed ln Lhe lungs are splder anglomas due Lo Av
flsLulas relaLed Lo hlgh esLrogen, Lherefore clear more CC
2
per breaLh Lhan a normal
50

woman. A loL of shunLlng occurrlng wlLhln lungs. 1hese splder anglomas go away
afLer dellvery of Lhe baby.

(e) LndoLoxlns over sLlmulaLe Lhe sysLem. All pLs ln endoLoxlc shock have resp
alkalosls. 1hey are also ln anaeroblc meLabollsm, produclng lacLlc acld, Lherefore are
also ln meLabollc acldosls. 1herefore, endoLoxlc resp alkalosls due Lo
oversLlmulaLlon, and meLabollc acldosls due wlLh normal pP.

(f) SallcylaLe overdose oversLlmulaLe resp cenLer, leadlng Lo resp alkalosls. Sallcyllc
acld ls an acld, hence meLabollc acldosls, and pP wlll be normal b/c Lhey balance e/o
ouL. (1lnnlLus ln sallcylaLe Cu also a MlxLu dlsorder!)

(g) 6 y/o chlld wlLh lnsplraLory sLrlder do a laLeral x-ray, and see LhumbprlnL slgn,
wlLh a swollen eplgloLLls. 1he dlagnosls ls acuLe eplgloLLlLls, due Lo P. lnfluenza,
P
b/c of Lhe vacclnaLlon. 1he MC of menlnglLls ln 1 monLh 18 yrs = n. menlnglLls.

(h) 3 monLh old croup, a larygloLracheobronchlLls dz due Lo paralnfluenza vlrus.
WanL Lo do a laLeral x-ray and see a sLeeple slgn. Where ls Lhe obsLrucLlon ln croup?
1rachea
(l) L shovlng food ln Lhelr mouLh (cafe coronary) Pelmllch maneuver, lf Lhey can
Lalk, leave alone and leL Lhem cough lL ouL.

([) ulaphragm lnnervaLed by Lhe phrenlc nerve le erb uuchene palsy, wlLh brachlal
plexus ln[ury, and chlld has resp dlfflculLy, and dlaphragm on rlghL slde ls elevaLed.
aralysls of Lhe dlaphragm wlll lead Lo lncreased CC
2
.

L C amyoLrophlc laLeral sclerosls LMn uMn
Lherefore cannoL breaLh b/c no lnnervaLlon Lo Lhe dlaphragm (le dlaphragm and
lnLercosLals are paralyzed)

(l)Culllaln-8arre ascendlng paralysls ln a paLlenL who a week ago had a resplraLory
lnfecLlon. 1he splnal fluld shows lncreased proLeln, sllghL lncrease ln lymphocyLes,
and a gram sLaln negaLlve. uz: Culllaln-8arre, demyellnaLlng dz

(o) ollo LMn uMn 1
muscle of resp wlll lead Lo resp acldosls.

(p) LunCS
51

CbsLrucLlve lung dz problem geLLlng alr ouL, compllance lncreased and elasLlclLy ls
decreased, Lherefore, have a resp acldosls.
ln resLrlcLlve lung dz, le Sarcoldosls and pneumonoclonloses, Lhere ls a problem ln
geLLlng alr ln Lherefore has a resp alkalosls (?)

Day 2

C u underwaLer: for every 30 fL, lncrease 1 aLm, (le 760 aL level, buL 30 fL lower
lL wlll be 2 aLm), Lhe reverse ls Lrue when you go Lo hlgh alLlLudes le aL Lop of mL eversL, Lhe
aLmospherlc pressure ls 200 aLm, sLlll breaLhlng 21 C
2
, breaLhlng Lhe same, buL aLmospherlc
pressure ls dlfferenL, dependlng on where you are.

lormula for calculaLlng: alveolar C
2
= (0.21 x aLmospherlc pressure) CC
2
/ .8

Plgh AlLlLude: (.21 x 200) 40mmPb/.8 = 2mmPg of alr ln alveoll, Lherefore wlll have Lo
hypervenLllaLe aL hlgh alLlLudes, b/c lower pCC
2
= lncreased C
2
(you PAvL Lo hypvervenLllaLe
oLherwlse you dle).

Powever, when you go under, Lhe aLm pressure lncreases, and Lhe nlLrogen gases are
dlssolved ln your Llssues, leadlng Lo an lncrease ln pressure. le 60 fL below, wanL Lo geL up
fasL, llke shaklng a soda boLLle, as you ascend, Lhe gas comes ouL of faL ln bubbles, Lhe
8v s Lo paln, and quadrlplegla, loss
of bladder conLrol. 8x = hyperbarlc C2 chamber.
52

CnA1Lk 4: NU1kI1ICN

I. Lat|ng d|sorders |nc|udes obes|ty, anorex|a, bu||m|a
ulfference beLween anorexla and bullmla?
A. Anorex|a
ulsLorLed body lmage, women wlLh anorexla can have dlsLorLed lmage, conLrol lssue,
Lhey have losL conLrol of everyLhlng ln Lhelr llfe, and Lhe only Lhlng LhaL Lhey can conLrol
over ls whaL Lhey puL ln Lhelr mouLh. WlLh a decrease of body faL and wL, Cn8P
decreases, Lherefore lSP and LP also decrease, leadlng Lo low esLrogen, as a resulL,
amenorrhea occurs, Anu predlsposes Lo osLeoporosls, as lf pL ls posLmenopausal.
Anorexlc people wlll evenLually develop osLeoporosls.
8x convlnce person Lo galn enough wL Lo brlng perlod back, noL blrLh conLrol.
(le flrsL sLep ln managemenL of P/dlabeLes = wL loss, as you lose adlpose, you
upregulaLe lnsulln reslsLance). ln anorexla, usually dle Lo cardlac dz (hearL fallure: hearL
[usL sLops).

8. 8u||m|a Nervosa
1. MeLabollc Alkalosls l mage problem Lhey can be obese, normal or
Lhln (no welghL lssue), however, Lhey blnge (eaL a loL), Lhen force Lhemselves Lo vomlL.
lc on boards: from vomlLlng, wear down enamel on LeeLh, so, brownlsh sLuff seen on
LeeLh ls [usL denLlne (eroslons seen on LeeLh). MeLabollc alkalosls from forced vomlLlng
wlll be seen. MeLabollc alkalols ls bad b.c Lhere ls a lefL shlfL curve, and Lhe
compensaLlon ls resp acldosls, whlch drops pC
2
, Lherefore wlll geL hypoxla wlLh
meLabollc alkalosls, and Lhe hearL do noL llke LhaL. 1he hearL already wlLh low C
2
wlll geL
vC -maLure venLrlcular conLracLlons), 881 phenom, Lhen v-flb, Lhen deaLh.
1herefore, meL alkalosls ls very dangerous ln lnduclng cardlac arryLhmlas, and Lhls
commonly occurs ln bullmlcs due Lo forced vomlLlng. L can also vomlL ouL blood
Mallory Welss Syndrome Lear ln dlsLal esophagus or proxlmal sLomach.

2. 8orhave syndrome, whlch ls worse. ln Lhe syndrome, Lhere ls a rupLure and alr and
secreLlons from Lhe esophagus geL lnLo Lhe pleural cavlLy, Lhe alr wlll dlssecL Lhrough
subcuLaneous Llssue, come around Lhe anLerlor medlasLlnum, whlch leads Lo Pemlmans
crunch
1 Lhrough lnLersLlal Llssue up lnLo Lhe
medlasLlnum, lndlcaLlng LhaL a rupLure occurred ln Lhe esophagus, Lhls ls anoLher
common Lhlng ln bullmlcs.
So, Lhere are 2 Lhlngs lmp ln bullmlcs: 1) MeLabollc alkalosls from vomlLlng (whlch can
lnduce arrLhymlas 2) 8

C. Cbes|ty W 8Ml
53

l 8Ml
morbldly obese. Maln compllcaLlon of obeslLy = P1n, wlLh P1n, leads Lo LvP, and
poLenLlally hearL fallure. MCC deaLh ln P1n = cardlac dz. CLher compllcaLlons of obeslLy
lnclude: gallbladder dz, cancers wlLh a loL of adlpose, you aromaLlze many 17-
keLosLerolds llke androsLenedlone lnLo esLrogens. 1herefore, wlll hyperesLrlnlsm (all
obese women have hyperesLrlnlsm), you are aL rlsk for esLrogen relaLed cancers le
breasL cancer, endomeLrlal carclnoma, colon cancer.

II. Ma|nutr|t|on

roLeln-calorle malnuLrlLlon:
1. Marasmus LoLal calorle deposlLlon, and wasLlng away of muscle, however, hlgh
chance of survlval lf Lhey geL food
2. kwashlorkor prob gonna dle, have carbs, buL no proLeln, also have anemlas, cellular
lmmunlLy probs (le no rxn Lo ags), low albumln levels, asclLes, faLLy llvers.
1hese klds are apaLheLlc and need Lo be force-fed, Lherefore, kld wlLh kwashlorkor ls
more llkely Lo dle Lhan chlld wlLh Marasmus. Lxample: kld wlLh edema, flaky dermaLlLls,
reddlsh halr (Cu def) kwashlorkor

III. V|tam|ns

A. D|fference between fat and water so|ub|e v|tam|ns:
1. laL soluble vlLamlns dlssolve ln faLs, lndlcaLlng LhaL Lhey are Laken up by
chymlomlcrons. 1he chymlomlcron wlll have A, u, L, and, k b/c Lhese are Lhe faL soluble
vlLamlns. laL soluble are more llkely Lo be sLored ln faL, so Lhe LoxlclLy ls much greaLer,
b/c lf lL ls waLer soluble, we [usL pee lL ouL.
MCC brlghL yellow urlne = vlLamlns
2. WaLer soluble vlLamlns

8. Iat so|ub|e v|tam|ns:
1. V|tam|n A
a. luncLlon: ls very lmp ln chlldren for growLh and can have fallure Lo Lhrlve ln vlL
A def. very lmporLanL ln lodopsln/rhodopsln wlLhln Lhe eye and Lhe flrsL slgn of vlL A
def ls nlghL bllndness whlch ls called nlcLolopla. vlL A also prevenLs sq meLaplasla.

b. Lxample of vlL A def: eye wlLh sq meLaplasla, goose bumps on back of arm called
folllcular hyperkeraLols. Lye ls llned wlLh cuboldal eplLhellum, when you geL sq
meLaplasla, wlll geL whlLe spoLs on Lhe eye. lf become exLenslve, grow over eye, and
can lead Lo sofLenlng of Lhe cornea (keraLomalacla), and leads Lo bllndness. 2
nd
MCC
bllndness globally = vlL A def. MCC bllndness globally = Lrachoma, MCC bllndness ln
54

uSA = dlabeLes. 1herefore, vlL A wlll prevenL sq meLaplasla, lf you are vlL A deflclenL
and a nonsmoker, a person can end up wlLh sq meLaplasla ln malnsLem bronchus and
bronchogenlc carclnoma.

c. 1oxlclLy: PypervlLamlnosls A ex. blg game hunLer LhaL eaLs bear llver and has
headaches. lncreased vlL A causes cerebral edema, also geL papllloedema (whlch
causes Lhe headache), can alsp lead Lo hernlaLlon and deaLh. 1here ls also an
lncrease of reLlnolc acld (used from LreaLlng acne and acuLe progranulocyLlc anemla).
1he reLlnolc acld LoxlclLy can lead Lo severe llver LoxlclLy. 1herefore,
hypervlLamlnosls of vlL A affecLs 2 areas: 1) cerebral edema (braln) 2) llver. Lxample:
lf have young lady pL on reLlnolc acld for acne, need Lo check llver enzymes and ask
for headaches (can be developlng papllloedema or cerebral edema relaLed Lo vlL A
LoxlclLy). Masslve amounL of vlL A ln bear llvers, and hunLer dles wlLh masslve
headaches or llver fallure

2. V|tam|n D = vL8? lmp on Lhe boards, MC source of vlL u ls from sunllghL.
a. CholesLerol ls Lhe
1. Maln componenL of our cell membranes
2. SLarLlng polnL for maklng blle salLs and blle aclds
3. llrsL compound LhaL sLarLs Lhe synLhesls of sLerold hormones ln Lhe adrenal
corLex
4. And Lhe 7-dehydrocholesLerol ln Lhe skln ls phoLoconverLed Lo vlLamln u.
1herefore we need cholesLerol! (makes blle salLs, hormones, cell membranes, and vlL
u).

b. Source: Sun ls Lhe mosL lmp source of vlL u. Lake baby ouL Lo expose Lo sunllghL
(no vlL u or vlL k ln breasL mllk, Lherefore musL be supplemenLed expose Lo sun for
vlL u).

c. SynLhesls of vlLamln u: 8eabsorbed ln Lhe [e[unum. undergoes 2 hydroxylaLlon
sLeps, flrsL ls ln Lhe llver, where lL ls 23 hydroxylaLed and Lhe 2
nd
ls ln Lhe kldney and
lLs 1 alpha hydroxylase. WhaL hormone puLs 1-alpha hydroxylase ln Lhe proxlmal
Lubule? 1P. 1P ls responslble for synLhesls of 1-a-hydroxylase and ls synLheslzed
ln Lhe proxlmal Lubule. (ACL ls from Lhe endoLhellal cells of Lhe pulmonary caplllary,
LC ls from Lhe endoLhellal cells of Lhe perlLubular caplllary). 1-a-hydroxylase ls Lhe
2
nd
hydroxylaLlon sLep, and now lL ls acLlve (Lhe flrsL was ln Lhe kldney).

d. vlL u funcLlon: reabsorb Ca and phosphorus from Lhe [e[unum. lL PAS Lo reabsorb
boLh of Lhese, b/c lLs maln [ob ls mlnerallzlng bone and carLllage. Pave Lo have
approprlaLe solublllLy producL Lo be able Lo do LhaL, Ca and phosphorus are
55

necessary Lo mlnerallze carLllage and bone (llke Lhe osLeold maklng bone).
1herefore, lL makes sense Lo reabsorb Ca and phosphorus b/c lL needs Lo make sure
LhaL boLh of Lhem are presenL ln adequaLe amounLs Lo have an adequaLe solublllLy
producL Lo mlnerallze bone.

e. araLhyrold Pormone (1P) luncLlons: (1)ls somewhaL relaLed Lo vlLamln u
meLabollsm, lL helps lasL sLep for hydroxylaLlon of vlL u syn. (2) 1P wlll lead Lo
reabsorpLlon of Ca ln Lhe early dlsLal Lubule (Lhls ls also where na ls reabsorbed, and
Lhlazldes block Lhls channel). AL LhaL locaLlon, Lhere ls a Ca channel, 1P helps
C C n
na, reabsorbed, Lherefore Ca has Lo sneak Lhrough channel, wlLh help of 1P.
1herefore, wlLh Lhlazldes, na ls blocked, leavlng Lhe Ca channel compleLely open, and
Lhe Lhlazldes wlll lead Lo hypercalcemla. 1herefore, use ln Ca sLone formers mosL
of sLone formers have hypercalclurea, Lhese pLs have Loo much Ca ln Lhelr urlne,
when Lhey are on Lhlazldes, Lhe drug Lakes Ca Cu1 of Lhe urlne, so Lhey do noL form
sLones. (3) 1P wlll decrease reabsorpLlon of phosphorus ln Lhe prox Lubule, and (4)
decrease Lhe reaccumulaLlon of blcarb, Loo.

f. vlLamln u and 1P and how Lhey work LogeLher:
<u ? maln funcLlon ls mlnerallzlng bone, and osLeoblasLs (bone bullders) are
lnvolved wlLh Lhls process, Lherefore Lhe recepLor for vlL u ls locaLed on Lhe
osLeoblasL. When vlL u hooks lnLo Lhe recepLor, lL causes Lhe release of alkallne
phosphaLase. So, when you are growlng bone or reheallng of a fracLure, you expecL
Lo see an lncrease ln alkallne phosphaLase, whlch makes Lhe approprlaLe solublllLy
producL Lo mlnerallzed carLllage and bone. knowlng LhaL 1n breaks down bone
(malnLalns Ca levels ln Lhe blood sLream) you would Lhlnk LhaL lLs recepLor would be
on Lhe osLeoclasL (cell normally breaks bone down). Powever, only one hormone
has a recepLor on osLoeclasLs and LhaL ls ca|c|ton|n. When calclLonln hooks lnLo Lhe
osLeoclasL recepLor, lL lnhlblLs Lhe osLeoclasL, and Lherefore ls used Lo LreaL
hypercalcemla. CalclLonln also used ln LreaLlng osLeoporosls. 1he recepLor for 1P ls
on Lhe osLeoblasL, buL noL sharlng Lhe same one as vlL u. When 1P hooks on Lhe
osLeoblasL, lL releases lL-1. AnoLher name for lL-1 ls osLeoclasL acLlvaLlng facLor
(oLher funcLlons of lL-1 are also lnvolved ln fever, sLlmulaLes Ab synLhesls, and 8 cell
sLlmulaLlon). So, lL-1 (released from Lhe osLeoblasL) acLlvaLes osLeoclasLs vla lL-1
release from osLeoblasL, and osLeoclasL ls slgnaled Lo break down bone Lo malnLaln
Ca levels ln our bloodsLream. Sex hormones keep lL-1 ln check, ln women, esLrogen
levels keep a check on lL-1 (do noL wanL Loo much osLeoclasL acLlvaLlon), ln men, lL ls
LesLosLerone LhaL keeps lL-1 ln check (puLs lnhlblLory effecL on lL-1 release from Lhe
osLeoblasL afLer 1P hooks ln). 1herefore, ln women, can see why Lhey geL
56

osLeoporosls lack of esLrogen = lL-1 noL ln check and breaklng more bone down
Lhan maklng (Lhls ls Lhe mechanlsm of posLmenopausal osLeoporosls).
1P ls more lnvolved ln malnLalnlng Ca levels ln our blood, whlle vlL u ls more
lnvolved ln mlnerallzlng our bones and carLllage.

g. vlLamln u deflclency: Many reasons: lack of sun, poor dleL, llver dz, renal dz.

Lxample: L
rlfampln all lnduce Lhe cyL p430 sysLem locaLed ln Lhe SL8. 1herefore, geL SL8
hyperplasla, Lherefore, you meLabollze drugs and oLher Lhlngs made ln Lhe llver,
lncludlng 23-hydroxyvlLa u 1
wlll cause a decrease ln vlL u, and any oLher drugs belng Laken.

Lxample: woman on blrLh conLrol pllls and Laklng phenyLoln, and she goL pregnanL,
1 ch lncreased Lhe meLabollsm of
esLrogen and progesLerone ln Lhe blrLh conLrol pllls, Lherefore noL enough levels Lo
prevenL pregnancy.
Lxample SL8
Camma gluLamyl Lransferase (CC1) enzyme of SL8! (look aL ln alcohollcs)

Lxample: MCC chronlc renal dz ln uSA: dlabeLes melllLus Lubular damage, so no 1-
a-hydroxylase, Lherefore lnacLlve vlL u. 1herefore, pLs wlLh chronlc renal fallure are
puL on 1-23-vlL u.

Lxample: lf someone geLs C1C vlL u, whaL sLeps does lL go Lhrough Lo become
meLabollcally acLlve? 23 hydroxylaLed ln llver, and 1-a-hydroxylaLed ln your kldney (lL
ls nC1 1, 23 vlL u Lhls ls a prescrlpLlon drug, and exLremely dangerous). Many
people have Lhe mlsconcepLlon LhaL Lhe vlLamln u ls already worklng. 1hls ls noL Lhe
case, pL musL have a funcLlonlng llver and kldney.

WlLh vlL u def ln klds = rlckeLs, vlL u def ln adulLs = osLeomalacla (sofL bones).
l ey wlll boLh be
sofL, Lherefore paLhologlc fracLures are common.

klds have dlfferenL a few Lhlngs LhaL are dlfferenL ln rlckeLs le cranloLoples, sofL
skulls (can acLually press ln and lL wlll recoll). 1hey can also geL rlckeLlc rosarles, b/c
Lhe osLeold ls locaLed ln Lhe cosLochondral [unc, and b/c Lhey are vlL u def, Lhere ls a
loL of normal osLeold walLlng Lo be mlnerallzed, buL noL an approprlaLe
Calclum/phosphorus solublllLy producL, wlll have excess osLeold wlLh llLLle bumps,
whlch ls called rlcke n
57


So, 2 Lhlngs you see ln klds and noL adulLs: 1) cranloLoples 2) rlckeLlc rosarles, rhe
resL ls Lhe same, wlLh paLhologlc fracLures belng Lhe maln problem.

h. 1oxlclLy/PypervlLamlnosls of vlL u: hypercalcemla, Lherefore rlsk of havlng Loo
many sLones ln Lhe urlne, and sLones ls a MCC compllcaLlon.
1ype 1 rlckeLs mlsslng Lhe 1-a-hydroxylase
1ype 2 rlckeLs mlsslng Lhe recepLor for vlL u

3. V|tam|n L
a. Maln funcLlon: malnLaln cell membranes and prevenL llpld peroxldaLlon of Lhe cell
membranes, ln oLher words, lL proLecLs Lhe cell membranes from belng broken down
by phosphollpase A (llpld peroxldaLlon, whlch ls free radlcal damage on Lhe cell
membrane, and ls prevenLed wlLh vlL L). CLher funcLlon: neuLrallzed oxldlzed LuL,
whlch ls far more aLherogenlc Lhan LuL by lLself. When LuL ls oxldlzed, lL ls way
more ln[urlous Lo Lhe cell Lhen when lL ls noL oxldlzed. vlL L wlll neuLrallze oxldlzed
LuL, Lherefore ls a cardloproLecLanL (vlL L and C boLh neuLrallze oxldlzed LuL). ln
summary: vlL L func = 1) proLecLs cell mem from free radlcal damage. 2) Cxldlzes free
LuL (Lhls ls Lhe LuL LhaL macrophages phagocyLose Lo produce foam cells, and leads
Lo aLheroscleroLlc plaques).

b. ueflclency of vlLamln L: ls seen buL ls very uncommon, and lf seen lf would be ln
klds wlLh cysLlc flbrosls, from blrLh, klds have resp probs and pancreas problems.
(look aL ln robblns, Loo). A kld LhaL has cysLlc flbrosls wlll have malabsorpLlon
problems, Lherefore whaL four vlLamlns should you glve hlm? CysLlc flbrosls pL has a
malabsorpLlon of faL, Lherefore Lhey wlll have malabsorpLlon of faL soluble vlLamlns
A, u, L, and k. vlL L def ln uSA ls usually seen ln cysLlc flbrosls paLlenLs.

c. Cllnlcal presenLaLlons: Cne of Lhe feaLures of vlL L def ls hemolyLlc anemla (vlL L
normally malnLalns Lhe lnLegrlLy of Lhe membrane), Lhls pL ls now suscepLlble Lo free
radlcal damage, damaged mem of 88C leads Lo hemolysls of 88C and hemolyLlc
anemla. AnoLher feaLure of vlL L are Lhlngs relaLed Lo myelln: posLerlor column dz,
splnal cerebellar probs. 1herefore, wlLh vlL L def, have neurologlcal problems and
hemolyLlc anemla.

d. vlLamln L LoxlclLy: anyLhlng more Lhan 1100 unlLs (average capsule ls 400 unlLs,
Lherefore, lf Lake 3 pllls, already Loxlc). vlLamln L LoxlclLy wlll lnhlblL synLhesls of
vlL k dependenL CoagulaLlon facLors (2, 7, 9, 10, proLeln C, proLeln S), ln oLher words,
you are anLlCoagulaLed. Lxample: pL wlLh Ml Lake anLloxldanLs, and asplrln, wlLh
anLerlor Ml, Lhey anLlCoagulaLe Lhe pL, and pL goes home on Lhree monLhs of
58

warfarln. normal ln8 raLlo, and Lakes loLs and loLs of vlL L and oLher vlLamlns. 1ake a
loL of vlL L and wlll help warfarln, leadlng Lo over anLlCoagulaLed sLaLe, (remember
LhaL warfarln blocks gamma carboxylaLlon of vlLamln k dep facLors). vlL L wlll
prevenL Lhe S?n1PLSlS of Lhese facLors. 1herefore, vlL L LoxlclLy ls synerglsLlc ln
acLlvlLy wlLh warfarln. Lxample: pL on warfarln, came home from Ml, ln8 raLlo ls
huge, why? 1aklng vlL L.

4. V|tam|n k
a. Sources: Can come from whaL we eaL, buL mosL ls synLheslzed by our colonlc
bacLerla (our anaerobes ln our guL) Lhls ls why we glve vlL k ln[ecLlons Lo our baby
when Lhey are born, Lhey only have 3 days worLh of vlL k from mom, buL afLer LhaL,
k
beLween days 3- k 1
geL hemorrhaglc dz of Lhe newborn (Lhls ls why we glve vlL k when Lhey are born),
afLer 3 days, Lhe bacLerla colonlze, and vlL ls made by Lhe baby.

b. MeLabollsm: 8acLerla make vlL k ln an lnacLlve form k2. k2 (lnacLlve form musL
be converLed by epoxlde reducLase Lo k1 (k1 ls Lhe acLlve form of vlLamln k). k1 wlll
gamma carboxylaLes Lhe vlL k dependenL facLors (2, 7, 9, 10, proLeln C and S).
Camma carboxylaLes requlres Lhe same undersLandlng as vlLamln C, ln vlL C lf you
C
carboxylaLlon of vlL k dep facLors acLually acLlvaLes Lhem Lo become funcLlonal. vlL k
dep facLors all have someLhlng ln common: (1)have Lo be acLlvaLed by vlL k1 and (2)
Lhey are Lhe only CoagulaLlon facLors LhaL are bound Lo a cloL by Calclum (Ca), so
Lhey have Lo be bound by Ca ln
you are anLlCoagulaLed. 1haL ls whaL gamma carboxylaLlon: gluLamlc acld resldues
are gamma carboxylaLed on Lhe vlL k dep facLors (whlch ls done wlLh k1), and allows
Ca Lo blnd Lhe facLors, Lherefore, lL keeps Lhem LogeLher and you are able Lo form a
C
Lhem Lo form a cloL (so, gammacarboxylaLlon ls Lhe anchor pL, so Ca can blnd Lo
form a cloL, slmllar Lo hydroxylaLlon of prollne and lyslne ln collagen synLhesls).

Warfarln blocks epoxlde reducLase, so all Lhe vlL k pL has ls k2 and no
gammacarboxylaLlon wlll occur. 1herefore, Lhe paLlenL ls anLlcoagulaLed.

c. vlLamln k deflclency: MCC vlL k def (ln hosplLal) = broa A
nd
MCC =
poor dleL, belng a newborn, malabsorpLlon. uef vlL k = hemorrhaglc dlaLhesls
(bleedlng lnLo skln or braln). know why newborn has vlL k def: Lxample: kld wlLh raL
polson raL polson ls warfarln, when raLs eaL lL, Lhey geL anLlCoagulaLed and dle.
1reaL wlLh lnLramuscular vlLamln k. Lxample: kld llved wlLh grandparenLs and
59

developed hemorrhaglc dlaLhesls: why? 8/c Lhe elderly were on warfarln, and kld
aLe Lhe warfarln, and led Lo Loxlc levels.

C. Water So|ub|e V|tam|ns: all are cofacLors ln ma[or blochemlcal paLhway
1. V|tam|n C:
a) Classlc example of vlLamln C deflclency: older person on Lea and LoasL dleL
lndlcaLlng LhaL Lhey are malnourlshed, pL geLs bleedlng of Lhe gums = scurvy, due Lo
vlL C def. vlL C ls responslble for hydroxylaLlon of prollne and lyslne, and Lhls occurs
C -LranslaLlonal modlflcaLlon occurs. Ls
have weak 1 l 8v
gums bleed. CeL bleedlng of Lhe gums, lnflammaLlon, and may loose LeeLh.

b) AssoclaLed quesLlon: whaL compllcaLlon ls assoclaLed wlLh severe hemophllla A?
PemearLhroses v C 8v
rupLure).

c) hyslcal dlagnosls of vlLamln C deflclency: Along wlLh Lhe Lea and LoasL dleL, Lhere
ls also perlfolllcular hemorrhage (hemorrhage around Lhe halr folllcles). See rlng
slderoblasL (nucleaLed 88C, and has Loo much lron ln Lhe mlLochondrla), rlng around
Lhe halr folllcle and also see cork screw halrs due Lo vlL C def. 1he Longue looks llke lL
hurLs and paLlenLs wlLh vlL C have a smooLh Longue glosslLls, wlLh kelosls around
ankles, plus a hemorrhaglc dlaLhesls = scurvy.

d) Lxcess vlLamln C: very common b/c pLs Lake way Loo much vlL C (6-8gm), maln
compllcaLlon ls 8enal sLones (lncreased urlc acld sLones, and oLher klnds of sLones).
vlLamln C and u boLh have LoxlclLy sLones.

e) vlLamln C ls used ln anclllary 8x for meLhemogloblnurla, lL ls a reduclng agenL and
a greaL scavenger hunLer for free radlcals (knocks Lhem off).

f) CofacLor ln blochemlcal paLhway: vlL C ls a cofacLor for converLlng Lhe
caLecholamlne nL lnLo Lpl.


2. V|tam|n 8
1
(1h|am|ne):
l
phosphaLe shunL, and pyruvaLe dehydrogenase, alpha keLo gluLaraLe dehydrogenase,
and alpha keLo acld dehydrogenase. All Lhe dehydrogenase rxns requlre Lhlamlne as
a cofacLor. yruvaLe dehydrogenase ls Lhe maln rxn LhaL converLs pyruvaLe lnLo
aceLyl CoA. yruvaLe can also be converLed Lo CAA wlLh a carboxylase enzyme.
60

When you comblne aceLyl CoA wlLh CAA, you make clLraLe, and you are ln Lhe 1CA
cycle.

b) So, lf Lhlamlne def, b/c lL ls lnvolved ln Lhe pyruvaLe dehydrogenase rxn (whlch
converLs pyruvaLe Lo aceLyl CoA), you wlll noL have a loL of aceLyl CoA around,
1CA
worklng efflclenLly, and LLSS A1. 1herefore, Lhe problem wlLh Lhlamlne def ls A1
depleLlon. When you go from pyruvaLe Lo aceLyl CoA, y nAuP
slnce Lhls ls ln Lhe mlLo, you geL 6 A1 (so, [usL from golng from pyruvaLe Lo aceLyl-
C A1 1CA A1 A1
geL from compleLely meLabollzlng glucose ls 38 A1, so, lf you are Lhlamlne def, you
A1 maln prob of Lhlamlne def ls A1 depleLlon.

l
berlberl). Pow does Lhls explaln weL/dry berlberl?

1) ury berlberl = perlpher W
llke an exam
l A1
synLhesls of myelln, wlLhouL myelln, you wlll geL perlpheral neuropaLhy and fooL
drop (due Lo common peroneal palsy), can geL wrlsL drop (radlal nerve palsy), and
claw hand (ulnar nerve palsy). W
nysLagmus. All of Lhese are due Lo demyellzaLlon.
2) WeL berlberl = hearL fallure, MCC Lhlamlne def = alcohol (noL pollshed rlce).
Alcohollcs are Lhe MC people wlLh Lhlamlne def. WeL berlberl ls referrlng Lo
cardlomyopaLhy cause: LPl wenL lnLo 8Pl whlch lead Lo plLLlng edema. PearL
needs A1 Lo funcLlon, Lherefore, Lhe pL wlLh have congesLlve cardlomyopaLhy,
Lhelr hearL wlll have blvenLrlcular enlargemenL (Lhe whole chesL wlll be hearL), wlLh
lefL and rlghL Pl (plLLlng edema ls a slgn of rlghL Pl due Lo lncreased hydrosLaLlc
pressure behlnd Lhe falled hearL). lf you glve lv Lhlamlne, can reverse, and ln some


d) Lxample: pL ln L8 glven lv of 3 dexLrose and normal sallne, all of sudden, pL
develops confuslon, nysLagmus, and aLaxla, and opLhalmaplegla. ulagnosls:
subcllnlcal Lhlamlne deflclency. As soon as Lhe glucose was hung up, Lhe pyruvaLe
CA W
encephalopaLhy. 1herefore, moral of Lhe sLory: glve lv Lhlamlne before hanglng up
lv glucose, especlally ln L8.

61

f) When people come ln comaLose or semlcomaLose, several Lhlngs you always do: 1)
30 glucose lf a hypoglycemla problem 2) naloxone (Cu) 3) lv Lhlamlne

3. V|tam|n 8
3
(N|ac|n):
Sllde: 8ash ln sun exposed area = pellagra (aka dermaLlLls), due Lo nlacln def (also
dlarrhea, dermaLlLls, demenLla), hyperplgmenLaLlon ln sun- C
necklace (dermaLlLls/pellagra),

nAu/nAu rxns (n sLands for nlcoLlnamlde, and Lhe nlcoLlnamlde was derlved from
nlacln). 1he L
pyruvaLe Lo aceLyl CoA = wenL from nAu Lo nAuP and nlacln ls lnvolved here.

1rypLophan
rce of nlacln, buL a good source.

nlcoLlnlc acld = leasL expenslve llpld lowerlng drug, see Lhe flushlng assoc wlLh lL,
supposed Lo Lake asplrln wlLh lL Lo remove Lhe flushlng relaLed Lo nlcoLlnlc acld (used
ln LreaLlng famlllal hyperllpldemla), lL ls Lhe uCC for elevaLed hyper1Cemla.

4. V|tam|n 8
2
(k|bof|av|n):
lAu/lMn rxns are rlboflavln cofacLor rxns (Lherefore, whenever you have lAu and
lMn rxns, Lhese are rlboflavln cofacLor rxns).
(nlacln for nAu/nAu rxns, and rlboflavln for lAu/lMn rxns).
Also, Lhe flrsL rxn: gluLaLhlone reducLase converLs oxldlzed gluLaLhlone lnLo
gluLaLhlone whlch rlboflavln ls a cofacLor for.

S. V|tam|n 8
6
(yr|dox|ne):
W l
succlnyl Coa, plus glyclne. 1he enzyme ls ALA synLhase, and Lhe cofacLor ls 8
6
.
1herefore, lL ls lmp Lo Lhe synLhesls of hemoglobln and heme proLelns. 1he
cyLochrome sysLem ls Lhe heme sysLem, Loo. Myoglobln ls dlfferenL from Pb (has
one heme group), whlle Pb has four heme groups. 1here ls also heme ln Lhe llver, ln
Lhe cyLochrome sysLem. yrldoxlne ls lnvolved ln Lhe synLhesls of heme, whlch ls ln
porphyrln. yrldoxlne ls ln Lhe Lransamlnases rxn. MosL abundanL subsLraLe from
maklng glucose ln Lhe fasLlng sLaLe = alanlne (aa from muscle
from muscle Lo geL glucose, vla gluconeogenesls). Pow can an aa be used Lo make
glucose? 1ransamlnaLlon. 1ransamlnaLlons (SCC1, SC1) from Lhe llver can Lake
Lransamlnases, Lhey Lake amlno groups ouL and puL Lhem lnLo oLher Lhlngs, lf you
Lake Lhe amlno group ouL of alanlne, Lhls produces pyruvaLe (an alpha keLo acld). lf
you Lake asparLaLe and Lake Lhe aa ouL, you have CAA, whlch ls a subsLraLe for
62

gluconeogenesls. lf you Lake pyruvaLe, and add an amlno group, can synLheslze
alanlne. lf you Lake CAA, and add an amlno group, you can make asparLaLe. 1hls ls
whaL Lhe Lransamlnases do, wlLh 8
6
as a cofacLor. 8
6
ls also lnvolved ln Lhe synLhesls
of neuroLransmlLLers. 1herefore, a chlld LhaL ls 8
6
deflclenL, Lhey end up wlLh severe
neurologlcal problems b/c no neuroLransmlLLers (8
6
lmp Lo synLheslzlng Lhe
neuroLransmlLLers). lmporLanL ln LransamlnaLlon, neuroLransmlLLer, and heme
synLhesls.

MCC def 8
6
def = lsonlazld, wlLhouL 8
6
, wlll develop neurologlc problems and
slderoblasLlc anemla relaLed Lo heme problem.

D. Cther |mportant co-factors

1. antothen|c ac|d ls relaLed Lo lA synLhase, noL Lhe raLe llmlLlng rxn, buL lmp ln
maklng palmlLlc acld (a 16 C lA), and helps ln maklng CoA (le aceLyl CoA, PMC CoA),
panLoLhenlc acld ls Lhe cofacLor for Lhese rxns.

2. 8|ot|n
CofacLor for oLher rxn of pyruvaLe Lo aceLyl Coa vla pyruvaLe dehydrogenase =
Lhlamlne ls Lhe cofacLor, whlle bloLln ls Lhe cofacLor for yruvaLe decarboxylase Lo
CAA. 1herefore, Lhlamlne helps form aceLyl CoA from pyruvaLe, whlle bloLln helps
form CAA from pyruvaLe.
lf you are def, need Lo eaL 20 raw eggs/day
ueflclency: geL a rash and go bald (alopecla). lf bloLln def, cannoL form CAA, and
cannoL from clLraLe elLher (Lhls ls Lhe flrsL sLep ln gluconeogenesls, Lherefore you can
end up wlLh fasLlng hypoglycemla). lf you bulld pyruvaLe, lL wlll be forced Lo go Lo
lacLlc acld.

3. 1race e|ements
a) Chromlum = glucose Lolerance facLor, and helps lnsulln do lLs [ob.
CaLmeal can also decrease glucose wlLh all Lhe flber, good for a Lype ll dlabeLlc Lo be
on chromlum.

b) Copper lysl oxldase puLs crossbrldge beLween collagen flbrlls and elasLlc Llssue.
1herefore, lf Cu def, have weak collagen and weak elasLlc Llssue, predlsposlng Lo
dlssecLlng aorLlc aneurysm. 8ed halr ln kwashlorkor also due Lo Cu def.

c) lluorlne needed Lo prevenL denLal carrles, Loo much fluorlne leads Lo whlLe, chalky
LeeLh, also ln Colorado b/c waLer has Loo much fluorlne. lL wlll also geL calclflcaLlon of
63

Lhe llgamenLs, where llgamenLs go lnLo bone, Lhe calclfled llgamenLs are sub[ecL Lo
rupLure, any good radlologlsL can deLecL fluorlne LoxlclLy.

d) Selenlum ln penLose phosphaLe shunL, form gluLaLhlone, and have rlboflavln
helplng LhaL enzyme. CluLaLhlone can neuLrallze peroxlde, and Lhls requlres
gluLaLhlone peroxldase, selenlum ls Lhe cofacLor for Lhls reacLlon. 1herefore, ln oLher
words, lL ls an anLloxldanL b/c lf you are def ln lL, Lhe gluLaLhlone cannoL breakdown
Lhe peroxlde. (vlL L usually comes wlLh selenlum so one works on gluLaLhlone,
whlle Lhe oLher proLecLs Lhe llpld membrane from free radlcal damage and scavenges
oxldlzed LuL).

e) Zlnc Lxample: older person wlLh dysgusla (abnormal LasLe) and anosmla (lack of
sell), smell and LasLe are boLh def ln zlnc def. Zlnc ls a meLalloenzyme, Lherefore lL
has a Lrace meLal as a cofacLor. Collagenase ls a meLalloenzyme b/c lL has zlnc ln lL,
and lL breaks down Lhe Lype 3 collagen, so you can form Lype 1 collagen. 1herefore,
lf deflclenL ln lL, wlll have poor wound heallng, and you geL a rash on Lhe face. So,
rash on face, dysgusla, anosmla, poor wound heallng = zlnc deflclency!!! ulabeLlcs
are zlnc def, unless Laklng supplemenLs.

4. D|etary f|ber (|nso|ub|e and so|ub|e) soluble flber can lower cholesLerol (noL Lhe
P
guL, lL wlll suck up waLer lnLo lL from Lhe colon, and also suck up bad Lhlngs llpopollc
acld. 93 of blle aclds and blle salLs are reabsorbed ln Lhe Lermlnal lleum. 1he 3 are
llpopollc aclds, whlch are carclnogenlc (produces colon cancer). So, flber (lnsoluble and
soluble), lL sucks Lhe llpopollc acld up, lnLo Lhe lnLerlor of Lhe sLool, so lL has no conLacL
wlLh Lhe bowel mucosa. lus, defecaLe more ofLen and Lherefore llpopollc aclds have
even less conLacL wlLh Lhe sLool. Women are lucky b/c Lhey recycle esLrogens, maln way
of excreLlng esLrogens ls ln blle and ouL of your sLool, buL a small of esLrogens are
recycled back lnLo Lhe sysLem. ?ou may noL necessarlly need LhaL, so, when on flber,
lncreased esLrogen ls passed ouL, Lherefore, decreaslng chance of breasL cancer, ovarlan
cancer, and uLerlne cancer b/c flber ln Lhe dleL.

IV. Spec|a| d|ets prote|n restr|ct|on
W eln ln?

1) 8enal fallure b/c excess proLeln broken down Lo ammonla and oLher Lhlngs Lhe
ammonla ls meLabollzed ln Lhe urea cycle, wlll have lncrease urea and Lhe kldney wlll have
Lo geL rld of more urea.

64

2) Clrrhosls of Lhe llver defecLlve urea cycle Lherefore cannoL meLabollze ammonla, mosL
of Lhe ammonla LhaL we have ln our bodles comes from bacLerla ln our colon LhaL have
urease ln Lhem (P. pylorl), and Lhey breakdown urea Lo ammonla ln our colon. Ammonla ls
reabsorbed, and supposed Lo go back Lo our llver and go lnLo Lhe urea cycle, become urea
and geL rld of lL. 8uL wlLh clrrhosls, no urea cycle, so Lhe ammonla levels lncrease ln Lhe
blood, leadlng Lo hepaLlc encephalopaLhy, menLal sLaLus abnormallLles, asLerlxls, also
caused by ocLpaneme, benzolc acld, neuroLransmlLLers.

So, Lwo slLuaLlons Lo resLrlcL proLeln: clrrhosls and chronlc renal fallure.
65

CnA1Lk S. NLCLASIA

I. Nomenc|ature: 89 vs. ma||gnant
A. Ma|n d|fference 89 usually does noL meLasLaslze, mallgnanL has Lhe capaclLy Lo
meLasLaslze. LxcepLlon: 89 Lumor LhaL meLasLaslze: lnvaslve mole (meLasLaslze Lo lungs,
buL goes away).

8. S||des:
a) MC skln cancer lnvAuLS buL does noL meLasLaslze: basal cell carclnoma.
b) uLerus: lelomyoma, MC 89 Lumor ln woman ls MC locaLed ln whlch organ? uLerus

c) llbrolds smooLh muscle, become very hard
d) MC 89 Lumor ln male (yellow) = llpoma
e) 89 Lumor of glands = adenomas (le adrenal adenoma Lhln adrenal corLex b/c lL ls
funcLlonal, lL could be maklng corLlsol, Lherefore suppresslng AC1P, and Lhe faslculaLa
A18CP? C l
mlneralocorLlcolds C
(Cl8 salLy sweeL sex)

f) 1ubular adenoma = MC precursor leslon for colon cancer (looks llke sLrawberry on a
sLlck)

C. Carc|noma vs. sarcoma
1. Carclnoma mallgnancy of eplLhellal Llssue (3 eplLhellal Llssues squamous,
glandular, and LranslLlonal)

a) Squamous carclnoma how Lo recognlze? LlLLle swlrls of lncreased redness (brlghL
red) called squamous pearls,

b) Clandular carclnoma 8ound glands, wlLh someLhlng ln Lhe mlddle =
adenocarclnoma

c) 1ranslLlonal cell carclnoma from bladder, ureLer, renal pelvls (from genlLal
urlnary LracL) all wlLh LranslLlonal eplLhellum

1herefore 3 carclnomas = squamous, adenocarclnoma, and LranslLlonal cell
carclnomas.

66

d) Lxample: MallgnanL melanoma flrsL sLep ln managemenL? Lxclslon (b9 verslon =
nevus), boLh are derlved from melanocyLes. 1hls ls Lhe mosL rapldly lncreaslng
cancer ln Lhe uSA, noL MC. 1hey are S- A apuL Lumors

e) ApuL 1umors: S- A apuL Lumors, apuL ls precursor upLake
decarboxylaLlon, meanlng LhaL Lhey are of neurosecreLory or neural cresL orlgln. 1herefore, on
LM, have neurosecreLory granules. S-100 Ag ls used Lo sLaln Lhlngs of apuL orlgln or neural
cresL orlgln (mosL, noL all, wlll Lake up LhaL Ag).
Lxamples of apuL Lumors: melanoma, small cell carclnoma of Lhe lung, bronchlal
carclnold, carclnold Lumor aL Lhe Llp of Lhe appendlx, neuroblasLoma (secreLory
Lumor), le 2 y/o wlLh Lumors all over skln, and on blopsy, lL ls S-
was from adrenal medulla, meLasLaslze Lo skln.

2. Sarcomas are mallgnancy of MLSLnCP?MAL Llssue (noL eplLhellal).
Sarcoma of smooLh muscle = leloymyosarcoma, SLrlaLed muscle =
rhabdomyosarcoma, laL = llposarcoma, (Lhese are mallgnancles of mesenchymal


Lxamples:
a) 8one, see meLaphysls, see C -ray
b/c Lhls Lumor acLually makes bone. ux = osLeogenlc sarcoma (bone maklng
sarcoma).

b) 8lopsy from glrl havlng necroLlc mass comlng ouL of her vaglna, vlmenLln and
- Lonal rhabdomyosarcoma (see sLrlaLlon of
muscle). 1hls ls Lhe MC sarcoma of chlldren (vaglna ln llLLle glrls and penls ln llLLle
boys)

c) Movable mass aL angle of [aw = mlxed Lumor
hlsLologlcally have Lwo dlfferenL Lypes of Llssue buL derlved from SAML cell layer (noL
a LeraLoma, whlch ls from Lhree cell layers),. MC overall sallvary gland Lumor (usually
b9) = mlxed Lumor

d) 1eraLoma = LooLh, halr, derlved from all Lhree cell layers (ecLoderm, mesoderm,
and endoderm) Aka germ cell Lumors b/c Lhey are LoLlpoLenLlal, and sLay mldllne.
Lx. anLerlor medlasLlnum, or plneal gland, Lherefore, LeraLomas are germ cell,
mldllne Lumors.

e) CysLlc LeraLoma of Lhe ovarles 8LC
confuse wlLh C C -ray,
67

see calclflcaLlons of Lhe pelvlc area! CysLlc LeraLoma (Lhe calclflcaLlons can be bone
or LeeLh). usually develop ln mldllne germ cell Lumor.

68

II. Nomenc|ature: Leukem|a and |ymphoma
MC on Lhe boards: Auer rod from myeloblasL, and hypersegmenLed neuLrophll from 812
and folaLe deflclency.

A. Leukem|a = mallgnancy of sLem cells ln Lhe 8M, and Lhey can meLasLaslze (llke all cancer)
and Lo lymph nodes, leadlng Lo generallzed lymphadenopaLhy and hepaLosplenomegaly.
uerlved from sLem cells ln Lhe marrow and meLasLaslze.

8. Ma||gnant |ymphoma: arlse from LMn nodes, and can meLasLaslze anywhere, lnclude
8M.

1he MC slLe ln body for lymphoma nC1 developlng ln lymph node: stomach
MosL exLranodal (ouLslde lymph node) prlmary lymphomas occur ln Lhe sLomach,
P. pylorl can produce Lhese.
2
nd
MCC locaLlon (lymphold organ ln Lhe Cl LracL) = 4? 0 (locaLed ln Lhe
Lermlnal lleum).

MC lymphoma = folllcular 8 cell lymphoma. 1hls ls an example of knocklng off apopLosls
gene -14:18 LranslocaLlon of a heavy chaln, when you geL Lhe LranslocaLlon, 8 cells wlll
make bcl-2, whlch lnacLlvaLes apopLoLlc gene ln Lhe 8 cell, Lherefore, Lhe apopLoLlc gene
ls lmmorLal, leads Lo cancer.

III. Nomenc|ature of 1rophob|ast|c 1umors
A. nydat|d|form mo|e, presenLs wlLh clusLer of grapes. lL manlfesLs ln Lhe flrsL LrlmesLer
wlLh slgns of preeclampsla (P, proLelnurla, edema ln Lhe flrsL LrlmesLer). Cn ulLrasound,
wlll see uLerus Loo large for lLs gesLaLlonal age, wlLh a snowsLorm appearance = classlc
compleLe mole, and can progress Lo chorlocarclnoma.

8. Chor|ocarc|noma mo|e ls a benlgn Lumor of Lhe chorlonlc vlllus, chorlonlc vllll are llned
wlLh LrophoblasLlc cells, lncludlng syncLloLrophoblasL on Lhe ouLslde (has conLacL wlLh Lhe
blood, from whlch C
2
ls exLracLed), under Lhe syncLloLrophoblasL ls Lhe cyLoLrophoblasL,
umblllcal
veln, whlch has Lhe mosL C
2
ln Lhe vessels of Lhe feLus.

So, hydaLldlform mole ls a 89 Lumor of Lhe WPCLL chorlonlc vlllus, and lL looks llke grapes
C
syncLloLrophoblasL and Lhe cyLoLrophoblasL (noL Lhe acLual chorlonlc vlllus). Whlch makes
hormones? 1he syncyLloLrophoblasL synLheslzes 8-PCC and human placenLal lacLogen
(growLh hormone of pregnancy So, when
gesLaLlonally derlved, and even when Lhey meLasLaslze Lo Lhe lungs, Lhey respond well Lo
69

chemoLherapy (meLhoLrexaLe, chlabucll). 1herefore, Lhese are hlghly mallgnanL Lumors,
buL go away wlLh chemoLherapy.

NI7q-vq-, 6k
LveryLhlng LhaL end ln oma ls noL necessarlly b9 le melanoma (mallgnanL Lumor of
melanocyLes), lymphoma (mallgnanL Lumor of lymph nodes)

Also, all LhaL ends ln oma ls noL necessarlly a neoplasm le hemarLoma = overgrowLh of
Llssue LhaL ls normally presenL ln LhaL area. Lxample: A bronchlal hemarLoma seen lung

granuloma). 1he polyp ln euLz !eghers syndrome ls a hemarLoma (noL even a neoplasm),
P MC polyp ln Cl) ls
8
sLomach) Lhls ls called a chorlsLoma, or heLeroLoplc reL.

M u
MC M u c mucosa LhaL ls
S
dlverLlculum? no, b/c lL ls ln Lhe small bowel (abouL 2 fL from Lhe lleocecal valve).
PemarLomas are non-neoplasLlc, and Lherefore do noL have cancer produclng poLenLlal.

V. Ma||gnant Ce||s
lncreased mlLoLlc raLe does noL mean cancer. WhaL makes mlLosls mallgnanL ls havlng an
).
key th|ng that determ|nes |f |t |s ma||gnant |s |ts ab|||ty to metastas|ze. MallgnanL cells
usually have a longer cell cycle Lhan Lhe cells Lhey derlved from. now many doub||ng t|mes
does |t take to get a tumor that can be detected c||n|ca||y? 30 doub||ng t|mes means LhaL
Lhe Lumor goes Lhrough Lhe cell cycle 30 Llmes, and a Lumor of one sonomeLer ln slze ls
produced, 10
9
ln mass. MallgnanL cells are lmmorLal
adheslon, lf Lhey were sLuck Lo each oLher, Lhey would have problems lnfllLraLlng Llssue.
MallgnanL cells have slmple blochemlcal sysLems, Lyplcally anaeroblc meLabollsm, and have
many enzymes such as proLeases (used Lo break Lhrough Llssue), collagenases (used Lo
break Lhrough 8M). 1hls ls whaL makes a mallgnanL cell mallgnanL.

VI. Mechan|sms of Metastas|s: |ymphat|c, hematogenous, seed|ng

A. Lymphat|c metastas|zes:
Pow do carc|nomas usually meLasLaslze? Lymph nodes Lhey draln Lo Lhelr reglonal
lymph nodes, le breasL cancer goes Lo axlllary nodes or lnLernal mammary nodes. lor
colon cancer, go Lo nodes around Lhem (Lhe local lymph nodes), same wlLh carclnoma of
70

Lhe esophagus. WhaL parL of Lhe lymph node do meLasLases go Lo? Subcapsular slnus.
lf Lhey can geL Lhrough Lhe lymph node, Lhey go Lo Lhe efferenL lymphaLlcs whlch dralns
lnLo Lhe Lhoraclc ducL, and Lhen lnLo Lhe subclavlan, and Lhen Lhey become
hemaLogenous. 1herefore, carclnoma can become hemaLogenous, Lhls means LhaL Lhey
1
sL
wenL Lhrough Lhe lymph nodes, now, Lhey can spread Lo oLher organs (le bone, llver,
eLc). 1hls ls beLLer Lhan sarcoma b/c can feel Lhe lymph nodes by cllnlcal exam and plck
up before lL spreads.

8. nematogenous metastas|zes:
Cn Lhe oLher hand, sarcomas do noL llke Lo go Lo lymph nodes. 1hey go rlghL Lhrough
8v characLerlzed by hemaLogenous spread
1 1
are a llLLle worse b/c Lhey lmmedlaLely go hemaLogenous, and do noL glve a clue LhaL
Lhey are spreadlng. Lxample: have anglosarcoma of Lhe breasL, would you do a radlcal
dlssecLlon of Lhe axllla? no, b/c anglosarcoma does noL go Lo Lhe lymph nodes,
Lherefore, do a slmple masLecLomy. lf lL ls breasL carclnoma, Lake breasL and
lumpecLomy and local axlllary lymph nodes and compleLe Lhe dlssecLlon.

LxcepLlons: lolllcular carclnoma of Lhe Lhyrold sklps lymph
8v
8enal adenocarclnoma goes Lo renal velns (also deLermlnes prognosls)
PepaLocellular carclnoma llke Lo aLLack Lhe vessels

ln general, carclnomas 1
sL
llke Lo go Lo lymph nodes, and Lhe have Lhe poLenLlal Lo
become hemaLogenous. Sarcomas go hemaLogenous, maklng Lhem dangerous.

C. Seed|ng: Classlcal Lxample: cancers LhaL are ln cavlLles and have a poLenLlal of seedlng,
llke llLLle mallgnanL lmplanLs. MosL ovarlan cancers are surface derlved cancers, Lherefore
derlved from llnlng around Lhe ovary, and Lhey seed llke llLLle lmplanLs. 1herefore, easy Lo
Lhrow ouL Lhese lmplanLs and for lL Lo meLasLaslze Lo Lhe omenLum, and lnLo Lhe pouch of
uouglas. 1he pouch of uouglas ls posLerlor Lo Lhe uLerus and anLerlor Lo Lhe recLum and ls
felL by dlglLal recLal exam. 1he pouch of uouglas ls Lo a woman, as Lhe prosLaLe gland ls Lo
Lhe man. lf you do a recLal on a man, and push forward, you wlll feel Lhe prosLaLe. lf you
do a recLal on a woman and push forward, Lhls ls Lhe pouch of uouglas. 1hls ls an lmp area
cloLLed
blood ln a rupLure ecLoplc pregnancy, where endomeLrlal lmplanLs go ln endomeLrlosls,
and where seedlng goes ln ovarlan cancers (pouch of uouglas). So, seedlng of ovarlan
cancer Lo Lhe omenLum and can acLually lnvade. Can also seed ln Lhe pleural cavlLy, for
example: perlpherally locaLed lung cancer LhaL can seed lnLo Lhe pleural cavlLy. C8M (MC
71

prlmary mallgnancy of Lhe braln ln adulLs) can seed lnLo Lhe splnal fluld and lmplanL lnLo
Lhe enLlre splnal cord, as can a medulloblasLoma ln a chlld.

So, Lhe 3 mechanlsms for meLasLasls are lymphaLlc, hemaLogenous, and seedlng.

VII. Most Common (MC) cancers
1 l

ln mosL cases, meLasLasls ls Lhe MC cancer ln an organ (noL a prlmary cancer). LxcepLlon:
renal adenocarclnoma (whlch ls more common Lhan meLasLasls Lo lL).

Lung: MC cancer ls meLasLasls from Lhe breasL cancer. 1herefore, MC cancer ln Lhe lung ls
breasL cancer. 1herefore, women are more llkely Lo geL lung cancer.

8one: MC cancer ln bone ls meLasLasls (noL mulLlple myeloma or osLeogenlc sarcoma). MC
cancer LhaL meLasLasls Lo bone ls breasL cancer b/c Lhe baLsom sysLem, lL ls a venous
complex golng from base of Lhe skull down Lo Lhe sacrum, and has no valves ln lL. 1he llLLle
LrlbuLarles communlcaLe wlLh Lhe vena cava and also go rlghL lnLo Lhe verLebral bodles.
1hen Lhey collecL around Lhe splnal cord and go up. lor example: a lady has a llLLle plug of
Lumor ln Lhe lnLercosLal veln, and bends down Lo plck up someLhlng off Lhe ground, whlch
causes Lhe cancer Lo be dlslodged from Lhe veln Lo Lhe vena cava Lo Lhe baLson plexus ln
Lhe verLebral bodles, and 3 monLhs laLer she ls complalnlng of lower back paln. All of a
sudden, she ls sLage four cancer.

MC bone meLasLasls 1C Lhe verLebral column. 2
nd
MC ls Lhe head of Lhe femur (ln a
woman, Lhls ls due Lo breasL cancer le breasL cancer ln head of femur, when Lhey
LhoughL lL was degeneraLlve arLhrlLls).

MC organ metastas|s to = |ymph nodes (carclnomas are more common Lhan sarcomas, and
carclnomas llke Lo go Lo lymph nodes, meanlng lL ls Lhe MC meLasLasls Lo)

L|ver: MC cancer of llver = meLasLasls from lung lnLo llver (noL colon colon ls 2
nd
b/c porLal
veln dralnage).

1est|cu|ar Cancer: Where would LesLlcular cancer meLasLaslze flrsL? araorLlc lymph nodes,
nC1 Lhe lngulnal lymph nodes b/c lL derlved from Lhe abdomen, and Lhen descended.
Lxample: semlnoma (mallgnanL) wlll meLasLaslze Lo paraorLlc nodes b/c LhaL ls where lL
came from

72

Left suprac|av|cu|ar node, aka V|rcqS . 1 MC v
nodes = sLomach cancer! 1here ls a mass ln Lhe lefL supraclavlcular nodes along wlLh wL loss
and eplgasLrlc dlsLress.

73

8one: 8esL LesL looklng for bone meLs? 8adlonuclelde scan. Lxample: everywhere LhaL ls
black ln a woman ls meLs from breasL cancer. MC bone meLasLasls Lo = verLebral column!

MeLs LhaL are |yt|c (break bone down) and meLs LhaL are b|ast|c (meLs go lnLo bone and
lnduce osLeoblasLlc response).

A. LyLlc MeLasLasls:
lor lyLlc meLs, Lhey can lead Lo paLhologlc fracLures and hypercalcemla.
Mu|t|p|e mye|oma wlLh punched ouL leslons b/c all mallgnanL plasma cells have lL-1 ln
Lhem (aka osLeoclasL acLlvaLlng facLor)

8. 8lasLlc meLasLasls:
lor blasLlc meLs, a|ka||ne phosphatase wlll be elevaLed. Lxample: Lhls ls a male wlLh
prosLaLe cancer (prosLaLe cancer ls blasLlc!), lL ls maklng bone and wlll release alkallne
phosphaLase

MC |ocat|on for mets = |umbar vertebrae
Lxample: 80 y/o man wlLh lower lumbar paln wlLh pL Lenderness, whaL ls flrsL sLep ln
managemenL? ulglLal recLal exam would be Lhe flrsL Lhlng Lo do b/c Lhls would be sLage
four dz, and Lhe prosLaLe ls palpable, so, Lhls ls Lhe easlesL and cheapesL LesL (noL SA,
or radlonuclelde bone scan Lo make sure lLs noL meLs).

LyLlc meLs have lucency (absence of bone) le verLebrae collapse
8lasLlc meLs have enLlLy on x ray

If you see any spec|men w|th mu|t|p|e |es|ons |n |t, |t |s ML1S (pr|mary cancers are
conf|ned to one area of the organ).

MC cancer braln = meLs
MC cancer klller ln men and women = lung cancer
MC prlmary slLe for cancer ln braln = lung
MC cancer ln lung = meLs from breasL

MC meLs Lo adrenal = lung Lherefore Lhey always do a C1 of Lhe hllar lymph nodes, and
adrenal glands ln Lhe sLaglng of all lung cancers.
8one = blasLlc, Lherefore Lhe mosL llkely cause ls prosLaLe cancer.

VIII. Sta|ns and LM used to he|p dx dz:

Sta|ns: desmln good sLaln for muscle le used for rhabdomyosarcoma
74

SLaln for keraLln (mosL carclnomas have keraLln ln lL, Lherefore sLaln for LhaL)
SLalns help lu dlff Lypes of Lumors
vlmenLln- mesenchymal cells

LM: used when noLhlng else helps
AupuL Lumor see neurosecreLory granules.
PlsLlocyLe Lumor (le hlsLlocyLosls x) see blrbeck granules, wlLh Cu 1
Muscle see acLln and myosln fllamenLs
vascular mallgnancy Wlbble palad bodles (have vWl ln Lhem), Lhey are of endoLhellal
orlgln
k

Ik. Cncogenes|s:
A. 8|g p|cture of oncogenes|s
1) lnlLlaLlon (muLaLlon le wlLhln Lhe cell cycle)
2) romoLlon (where mulLlple coples of Lhe muLaLlon are made)
3) rogresslon (sub-speclallzlng) dlff Lypes of cancer cells have dlff func mallgnanL cells
wlLh one purpose Lo klll you. ulff cells wlLh dlff func: some sLay where Lhey are, some
lnvade (and are glven speclal Lhlngs for lL Lo be able Lo lnvade), some have speclal
recepLors Lo home ln Lo speclflc organs, some reslsL chemo, some spread, some make
enzymes Lo peneLraLe Llssues.

2 seLs of genes lnvolved wlLh cancer:
1) lnvolved ln growLh process (cell cycle relaLed)
2) Cenes LhaL suppress Lhlngs (suppressor genes)

8. 1h|ngs that are |nvo|ved |n try|ng to get a ce|| to d|v|de:
Cl Cl proLooncogenes
acLlvaLed, and have normal funcLlon. When Lhey have been acLlvaLed, Lhey become
oncogenes, whlch are bad and become cancerous. CerLaln proLooncogenes code for
growLh facLors le sls Cl

A Cl
Lo make recepLors le erb-2 = breasL cancer, whlch codes for a recepLor and reL = seen ln
MLn syndrome (MLn l and lla and llb).

We have Lo send a message Lo Lhe nucleus, so have anoLher seL of genes, whose [ob ls Lo
send Lhe message, some locaLed ln Lhe cell membrane. Lxample: ras proLooncogene sends
C1
75

messenger sysLem. AnoLher example: abl proLooncogene whlch llves ln Lhe cyLosol, very
close Lo Lhe nuclear membrane and also ls lnvolved ln messages.

Who ls Lhe messenger senL Lo? 1he message ls senL Lo a group of proLooncogenes ln Lhe
nucleus. Cnce LhaL message ls senL Lo Lhem, Lhere ls sLlmulaLlon of nuclear LranscrlpLlon of
LhaL message, ln oLher words, Lhe cell dlvldes and makes whaLever lL ls supposed Lo make.
C|ass|c protooncogenes there are myc protooncogenes = n-myc and c-myc (n-myc |s for
neurob|astoma, and c-myc |s for 8urk|tts |ymphoma).

S Cl nd messages
(whlch are ofLen phosphorylaLed proLelns). Lxample le lnsulln hooks lnLo recepLor on
adlpose and acLlvaLed Lyroslne klnase (locaLed rlghL on Lhe recepLor), whlch makes a
phosphorylaLed producL, goes Lo Lhe nucleus (Lo dlvlde), and also goes Lo CA and aLLaches
Lo CLu1-
recepLor for glucose. 1herefore Lhe messages go Lo nuclear Lranscrlbers ln Lhe nucleus and
Lhese are myc oncogenes.

1he suppressor genes are contro|||ng the ce|| cyc|e. 1he 2 most |mp are kb suppressor
gene and pS3 suppressor gene. normally, Lhey conLrol Lhe cell cycle and do noL leL cell
S l S

Pow do we lnlLlaLe a cell? MuLaLlonsmechanlsms: usually a polnL muLaLlon le subsLlLuLes
aa for e/o. 1 . All suppressor
C
AmpllflcaLlon make mulLlple coples (erb-2 ls an ampllflcaLlon sysLem) and

1ranslocaLlon CML LranslocaLlon of abl
C
clusLer reglon of Lhe fuslon gene, and b/c of Lhe Lyroslne klnase acLlvlLy, lL sends a message
and sLem cells keep dlvldlng, aka . AnoLher example: Cancer assoc wlLh
LpsLeln 8arr vlrus
8 8 L
barr vlrus on all 8 cells Cu 21, when lL hooks on Lo recepLor, lL causes 8 cells Lo become
plasma cells and make Ab (Lherefore, Lhls vlrus ls an amazlng sLlmulaLlng of Ab synLhesls, as
ls Lhe CMv vlrus.)
1he more a cell dlvldes, Lhe worse lL ls lf someLhlng happens Lo lL, le L8v vlrus , 8,14
LranslocaLlon of myc oncogenes from 8 Lo 14 and all of a sudden you are maklng mulLlple
coples, and leads Lo lymphoma (greaLer chance LhaL you do someLhlng, Lhe greaLer chance
LhaL you wlll screw up).

76

lolllcular 8 cell lymphoma LranslocaLlon of 14:18, lnacLlvaLlon of suppressor gene.

1rans|ocat|on 1S:17 = acute progranu|ocyt|c |eukem|a, kx V|t A (ret|no|c ac|d) b]c |t
matures the b|asts, therefore the ma||gnant ce|| becomes 89.

C. Suppressor genes
Suppressor genes suppress, Lherefore lf knocked off, whaLever Lhey were suppresslng
keeps on golng. key suppressor genes: pS3, kb gene, adenomatos po|ypos|s co|| (fam|||a|
po|ypos|s), neurof|bromatos|s, ->S v , brca1 and 2 (boLh lnvolved ln unA
brca1 can be breasL
cancer, ovarlan cancer, or oLhers, brca2 |s 1C1ALL re|ated to breast cancer. Cnly 13 of
breasL cancers have geneLlc assoc wlLh Lhese genes, Lherefore, mosL cases are sporadlc.

k. Common th|ngs that pred|spose mutat|ons:
roLooncogenes are acLlvaLed, whlle suppressor genes are lnacLlvaLed
3 maln ways Lhls occurs: chemlcals, vlruses, radlaLlon

A. Chem|ca|s:
Whlch of Lhe Lhree ls mosL common ln lnlLlaLlng a cell produclng a muLaLlon? Chem|ca|s
smok|ng = MCC death |n USA due to po|ycyc||c hydrocarbons.
8y lLself, smoklng ls MC Lhan vlrally lnduced or radlaLlon lnduced cancers. Smoklng
causes lung cancer, squamous cancer of Lhe mouLh, larynx, lung, pancreas, bladder, and


MCC paplllary Lumor of Lhe bladder = LranslLlonal cancer (smoklng)
WhaL lf you worked ln a dye lndusLry? Anlllne

]0 uo 0 ]8&? 8&>\u/ & 8 &80\u/ u
cyto|ogy and saw ce||s, what drug |s pt on? Cyc|ophospham|de (hemorrhag|c cyst|t|s),
prevent w|th mesna, and can cause trans|t|ona| ce|| carc|noma (therefore acts as a
carc|nogen!)

Lung cancer MCC = polycycllc hydrocarbons from smoke, mosL ofLen assoc wlLh
smoklng ls small cell and squamous,

8. V|ruses:
v u k
Lo PPv 8)

77

8urk|tts, due to Lpste|n barr var|es wh|ch a|so causes nasopharyngea| carc|noma, esp.
|n Ch|nese

||ver nepatoce||u|ar carc|noma due to hepat|t|s 8 from As|a, a|so due to a mo|d
#$%#&'()*" +," combo of hep 8, c|rrhos|s, p|us af|atox|n makes |s common |n As|a, can
a|so be caused by hep C

Plv ls assoc wlLh prlmary CnS lymphoma. 1hey wlll ask: Lhe rapldly lncreaslng lncldence
of prlmary CnS lymphoma can be dlrecLly aLLrlbuLed Lo whaL?
Plv

Pv causes squamous cancer of cervlx, vaglna, and vulva, and anus of homosexuals due
Lo unproLecLed lnLercourse, due Lo Pv 16, 18, 31. 1hls vlrus causes anal squamous cell
carclnoma ln homosexuals. 1he vlrus works by maklng Lwo proLelns, L6 wh|ch knocks
off pS3, wh||e L7 knocks of kb.

C. kad|at|on
MC cancer assoc w|th rad|at|on = |eukem|a
MC |eukem|a assoc w|th rad|at|on = CML (9, 22 trans|ocat|on of ab|)

aplllary carclnoma of Lhyrold ls also commonly seen as a resulL of radlaLlon. Lxample:
pL had radlaLlon ln head and neck, and has nonLender nodular masses ln cervlcal reglon
= meLasLaLlc paplllary carclnoma of Lhe Lhyrold relaLed Lo lonlzlng radlaLlon.

Lxample: osLeogenlc sarcoma

Lxample: whlch medlcal professlon ls mosL sub[ecL Lo leukemla? 8adlologlsL, leukemlas
LhaL are commonly lnvolved
wlLh Lhls.

Lxample: lf you have !acob CruLzfelL dz, whaL dr are you? neuro-aLhologlsL (bc work
wlLh bralns and prlons)

Lxample: basal cell carclnoma (plc), mulLlfocal, Lhls ls non lonlzlng radlaLlon (lonlzlng
radlaLlon ls Lhe bad sLuff). 1hls ls uv 8 llghL (b ls bad), uv A llghL ls for fluoresclng

(Lherefore used by dermaLologlsLs), aka black llghL. uv 8 llghL ls whaL you proLecL
yourself from Lo prevenL geLLlng skln cancers (basal cell = MC, Lhen squamous cell, Lhen
melanoma). uv u = Lhymldlne dlmmers

78

Lxample: leslon ln sun exposed areas LhaL ls scraped off and grows back aka solar
(acLlnc) keraLosls, lL predlsposes Lo squamous dysplasla. Arsenlc ls a meLal LhaL ls
assoclaLed wlLh skln cancer. 8ang|adesh has bad water supp|y wh|ch conta|ns arsen|c,
therefore they have a h|gh number of squamous sk|n cancers, and w|th t|me |t can
|ead to cancer of the |ung, and ang|osarcoma of the ||ver.

Lxample: kld wlLh whlLe eye reflex reLlnoblasLoma 1
l
l A one

muLaLlon on Lhe oLher chromosome ln order Lo develop reLlnoblasLoma. Wh|te eye
ref|ex |s not MC due to ret|nob|astoma the MCC |s congen|ta| cataract (wh|ch can be
due to CMV, rube||a, or any congen|ta| |nfect|ons). Wh|ch drug pred|sposes to
D --] qk -q q-vS >
cataracts.

79

kI. Genet|c dz

keroderma p|gmentosa sun exposed areas, auLo recesslve, can cause all skln cancers
(8CC, SCC, and melanomas), and the defect |s |n DNA repa|r enzymes. CLher unA repalr
defecLs are assoclaLed wlLh 88CA1 and 88CA2, p33, Lhey spllce ouL Lhe defecLs, Lhls group
ls called Lhe chromosomal lnsLablllLy syndromes wlskoLL Aldrlch, 8looms, ALaxla
1 l unA

8as|c ru|e of thumb for 8CC and SCC:
Upper ||p and up |s basa| ce|| carc|noma,
|ower ||p and down |s squamous ce||
(therefore, |es|on on |ower ||p = sq ce||, |es|on on upper ||p = basa| ce||)

Lxample: lnslde nose ls 8CC, b/c above Lhe upper llp

Lxample: kelold sq cell carclnomas and 3
rd
degree burns and sq cell carclnoma developlng
S
wherever Lhere ls consLanL lrrlLaLlon, and dlvlslon of cells relaLed Lo lrrlLaLlon, Lhere ls an
lncrease suscepLlblllLy Lo cancer. 1hls does noL hold Lrue for scar cancer Llssue relaLed
cancers of Lhe lungs or adenocarclnoma ([usL applles Lo Lhlngs on Lhe skln le burns and
dralnlng of slnus LracLs).

Cnly bacLerla assoc wlLh cancer? P. pylorl adenocarclnoma and low grade mallgnanL
lymphomas.

kII. Grade vs Stage

A. Grade = what does |t |ook ||ke? 1he Lerm well dlfferenLlaLed means LhaL Lhe Lumor ls
maklng s W
Lhe cells are anaplasLlc, poorly dlfferenLlaLed under Lhe mlcroscope, and lf you cannoL Lell

Lxample: sq cell carclnoma can see lu
Lxample: see gland llke spaces, can lu so lLs low grade

8. Stage = (1NM) MC sLaglng sysLem, goes from leasL lmp Lo mosL lmp (1nM)
Lxample: breasL cancer wlLh axlllary node lnvolvemenL, Lherefore, Lhe n M
worse, b/c lL lndlcaLes LhaL cancer has spread Lo oLher organs llke bone, eLc.
!

1=slze of Lumor, lf Lumor ls over 2 sonomeLers, lL has a chance of meLs
80

N=nodes (nexL mosL lmp for prognosls)
M=meLs ouLslde of nodes (mosL lmp prognosLlc facLor)
SLage ls more lmporLanL Lhan grade for prognosls, and wlLhln sLaglng, M ls Lhe mosL lmp
facLor for prognosls
Lxample: pL wlLh prosLaLe cancer, whlch of followlng has lL Lhe worsL? 1he answer cholces
were cancer llmlLed Lo prosLaLe, lL wenL lnLo semlnal veslcles, lL lnvolved Lhe wall of
A M
1nM sysLem Lhls le ls sLage 4 by deflnlLlon=meLs)

Lxample: a sllde of a colon cancer and a lymph node: whaL ls mosL lmporLanL slze of
Lumor or lymph node lnvolvemenL? Lymph node. lf lL was also ln Lhe llver, whaL ls mosL
lmp? Llver speclmen ls Lhe mosL lmp prognosLlc facLor.

kIII. nost defenses mosL lmporLanL ls CyLoLoxlc Cu8 1 cell
CLhers nk A P?
l MPC l A 1
cells, Lhey do Lhls by puLLlng ln perforlns, whlch acLlvaLe caspasases, and Lhls leads Lo
apopLosls (Lhe slgnal, from Lhe perforlns, acLlvaLe Lhe caspasases, whlch have proLeases, whlch
break down Lhe nucleus and mlLochondrla, and cell dles, wlLhouL any lnflammaLory lnfllLraLe).

kIV. Cther d|seases seen |n ma||gnancy:
A. Cachex|a cause ls 1nl alpha, lL ls lrreverslble
Cnce you see a pL wlLh dlssemlnaLed cancer abouL Lo go lnLo caLabollc sLaLe, can glve Lhen
W 1nl-
alpha)

8. Many hemato|og|c causes of anem|a seen |n ma||gnancy
MC anemla ln mallgnancy ls Anemla of chronlc dlsease (Lhls ls Lhe overall mosL common)

Co|on cancer: |eft s|de obstructs w] r|ght s|de b|eeds, |f you have k1 s|de b|eed |n co|on
cancer, Ie def anem|a |s very common.

MeLs Lo 8M and replace 8M

Cr, use chemoLherapy drugs LhaL are cell cycle speclflc or cell cycle nonspeclflc Lhey wlpe
ouL Lhe marrow

Can have auLolmmune mechanlsm wlLh cerLaln mallgnanL dz.

C. Assoc|at|ons w|th d|ssem|nated cancers:
81

1. MosL pLs wlLh dlssemlnaLed cancers are hypercoagu|ab|e, meanlng LhaL Lhey have a
Lendency for formlng cloLs. Classlc Lxample: a pL wlLh palnless [aundlce, lefL
supraclavlcular node (Lhls ls a dlsLracLer), had llghL color sLools, leslons LhaL [ump from
one parL of body Lo nexL
due Lo carclnoma of Lhe head of Lhe pancreas). ancreaLlc cancers can ALSC meLs Lo

a vascular problem ln Lhe velns LhaL [umps from one place Lo Lhe nexL.
2. AnoLher common Lhlng seen ls dlssemlnaLed cancers ls thrombocytos|s an elevaLed
plaLeleL counL. CLher causes of LhrombocyLosls: le def, splenecLomy (le see scar on
abdomen), 18, anemlas. lf you cannoL flnd any obvlous cause of LhrombocyLosls Lhen
Lhe cause ls cancer.
40 of dlssemlnaLed cancers are LhrombocyLosls
Cr a do a sLool gualc for colon cancer

D. MCC fever |n ma||gnancy = gram neg. |nfect|on. An L. coll lf you have an lndwelllng
caLheLer, seudomonas lf you have a resplraLor, sLaph aureus can also be Lhe cause from

MCC deaLh ln cancer = lnfecLlon

kV. araneop|ast|c syndromes
1hese are slgns and someLlmes sympLoms saylng LhaL you may have an underlylng cancer
presenL. lLs lmporLanL b/c when you recognlze Lhe slgns and sympLoms, Lhen you can caLch
Lhe cancer before lL meLasLaslze.

MC araneop|ast|c syndrome = hyperca|cem|a
2 mechanlsm for hypercalcemla ln mallgnancy:

1) meLs Lo bone, produce a chemlcal (lL-1, CL
2
, boLh of whlch acLlvaLe osLeoclasLs) LhaL
produces lyLlc leslons ln bone, and you geL hypercalcemla

2) renal adenocarclnoma or squamous carclnoma of malnsLem bronchus LhaL slLs Lhere and
makes 1P-llke pepLlde and causes hypercalcemla b/c lL acLs llke 1P and breaks down
1

Lxample: 2 black leslons boLh are markers for gasLrlc adenocarclnoma, usually under Lhe
arm called acanLhosls nlgrlcans, and oLher ls called seborrhelc keraLosls (Lhese are noL
neoplasms), however, when Lhese suddenly develop overnlghL, you geL mulLlple
ouLcropplngs (lesserr Lree-ar slgn), and Lhe ouLcropplngs ls a phenoLyplc marker for
gastroadenocarc|noma, Lhls ls easy Lo remember b/c 2 black leslons are markers from
gasLroadenocarclnoma.
82


Lxample: c|ubb|ng lnflammaLlon beneaLh on Lhe bone called perlosLlLls, lnflamm of
underlylng bone causes prollferaLlon of Lhe sofL Llssue around lL, whlch leads Lo clubblng
(called hyperLrophlc osLeoarLhropaLhy). Clubblng ls noL always assoc wlLh cancer, also
l8S 8

Lxample: leasL common collagen vascular dz, buL Lhe mosL ofLen assoc wlLh a cerLaln
cancer. 1hey have an elevaLlon of serum Ck, Lhls ls dermaLomyoslLls, raccoon eyes, so you
see lnflammaLlon of skln and muscle, hlgh assoc wlLh leukemlas, lymphomas and lung
cancer. paLches of knuckles

Lxample: vegeLaLlons (sLerlle) on Lhe mlLral valve assoc wlLh mucous produclng cancers
such as colon cancer, Lhls ls called maranLlc endocardlLls-aka nonbacLerlal LhromboLlc
endocardlLls, Lhey are noL lnfecLlons and Lhese maranLlc vegeLaLlons are assoc wlLh mucous
secreLlng colon cancers. Can Lhey embollze? ?es. ?ou wlll need hlsLory Lo separaLe from
rheumaLlc fever, buL hlsLory wlll relaLe more Lo colon cancer (le polyarLhrlLls)

Lxample C cancer ln Lhe lung = small cell carclnoma, whlch ls
secreLlng elLher AuP or AC1P, also, for small cell, Lhey are apuL Lumors,
S-100 Ag poslLlve, neural cresL orlgln, neural
secreLory granules.
Lxample: Pypercalcemla or secondary polycyLhemla: renal adenocarclnoma (can make 1P
llke pepLlde and/or LC).

Lxamp|e: nypog|ycem|a or secondary po|ycythem|a: nepatoce||u|ar carc|noma (they can
make LC or |nsu||n-||ke factor).

Lxample P C
be converLed Lo amylold (calclLonln) medullary carclnoma of Lhe Lhyrold.

kVI. 1umor markers

A. 2 markers assoclaLed wlLh 1esLlcular cancer alpha feLo proLeln (Al) (whlch ls really Lhe
albumln of a feLus) and PCC. Al ls a maker foryolk sac Lumor (endodermal slnus Lumor). So
Lhe Lumors ln klds are yolk sac Lumors (alpha feLo proLeln)

Al ls also assoc wlLh PepaLocellular carclnoma, lncreased ln neural Lube defecLs (musL be on
l u Al

83

Marker for mallgnancy ln bone, assoc wlLh monoclonal splke: 8ence !ones roLelns (llghL chaln
lg), assoc wlLh MulLlple Myeloma.

1umor marker for prosLaLe cancer: SA, noL sp for cancer b/c lL can be also lncreased ln
hyperplasla, lL ls senslLlve buL noL speclflc. lf you do a recLal exam, lL ls noL lncreased. SA ls
nC1 an enzyme, lL ls an Ag and ls wlLhln Lhe acLual cell. lL wlll noL lncrease wlLh a recLal exam.

8reasL cancer (surface derlved) 13, 3.
CLA123: Cvarlan cancer
CLA Ag for colon cancer, and someLlmes used for small cell, and breasL ca. CLA can be a parL
of an lmmune complex, and wlll geL CLA: anLl-CLA lmmune complexes whlch deposlL ln Lhe
kldney, and lead Lo nephroLlc syndrome Lhls ls dlffuse membranous glomerulonephrlLls = MC
overall cause of nephroLlc syndrome. Many of Lhese are relaLed Lo mallgnancy b/c CLA can be
Lhe Ag LhaL ls deposlLs ln Lhe glomerull.
woman wlLh a LrophoblasLlc mole, whaL would you geL? 8eLa PCC

W MC C 8 l
medulloblasLoma. All asLrocyLomas are 89 (lf asked whaL ls Lhe mosL common mallgnanL
prlmary Lumor, and Lhen Lhe answer ls medulloblasLoma, whlch derlves from cerebellum). MC
acLual Lumor of Lhe braln cerebellar Lumor derlved from asLrocyLes,

MC ch||dhood cancer = ALL leukemla (oLher chlldhood Lumors lnclude CnS Lumors,
8 L
sklnnlng), embryonal rhabdomyosarcoma.)

Adu|ts: lncldence:
ln woman: breasL, lung, colon
ln men: prosLaLe, lung, and colon

klllers: lung ls #1 ln boLh (followed by prosLaLe/breasL and colon)
2
nd
MC cancer and cancer klller ln men and women comblned = colon

1herefore, from age 30 and on, you should geL a recLal exam and a sLool gualc.
AfLer 30, MCC can

MC gyn cancer: endomeLrlal (#2 ls ovarlan, and #3 ls cervlx)
Cervlx ls leasL common b/c ap smear. When you do a cervlcal pap, plcklng up cervlcal
e hlghesL).
8/c cervlcal pap smears, Lhe lncldence of cervlcal cancer has gone down slgnlflcanLly b/c Lhe
deLecLlon of Lhe precursor leslon, cervlcal dysplasla. So, b/c cervlcal ap smear, lncldence of
84

cervlcal cancer has gone down dramaLlcally (plcklng up Lhe precursor leslon), wlLh
mammography, Lhe lncldence of breasL cancer decreases, same wlLh SA.

MC Gyn cancer k|||er: ovarlan (#2 = cervlcal, #3 = endomeLrlal), Lherefore Lo remember, Lhe
MC has Lhe besL prognosls endomeLrlal ls MC and has Lhe besL prognosls.

W P8v

MC lnfecLlon LransmlLLed by accldenLal needle sLlck ln Lhe hosplLal = PepaLlLls 8

8/c vlral burden of PepaLlLls 8 ls greaLer Lhan any lnfecLlon, even more so Lhan Plv.

So, wlLh Lhe P 8 P 8 P u
(requlres Pep 8), and (3) hepaLocellular carclnoma (relaLed Lo PepaLlLls 8 relaLed clrrhosls).

Pow do you eradlcaLe hepaLocellular carclnoma? vacclnaLlon (le ln Lhe lar LasL).
85

CnA1Lk 6. nLMA1CLCG: k8C

I. 1h|nk b|g p|cture.

Iuuku---Sk le def = MC and Anemla of chronlc dz, Lhalassemlas,
slderoblasLlc anemlas
7)<C4)u&\u?4 812/lolaLe def = MC, usually folaLe def ln an alcohollc
C. MCV 80-k f- -Sk low reLlculocyLe cL correcLed: aplasLlc anemla,
renal dz, hlgh correcLed reLlculocyLe cL: hemolyLlc anemlas heredlLary spherocyLosls,
slckle cell, C6u def, auLolmmune hemolyLlc anemla, mlcroanglopaLhlc

II. ket|cu|ocyte count: 8eLlculocyLe counL nexL Lo C8C ls Lhe flrsL sLep ln Lhe work up of any
anemlas. WhaL ls reLlculocyLe? ?oung 88C. ln 24 hrs, a reLlculocyLe wlll become a maLure 88C
wlLh a blconcave dlsk.

lf you have an anemla, Lhe reLlculocyLe counL ls lmp b/c lL Lells you where Lhe problem ls: ls
Lhe prob ln Lhe 8M ln maklng Lhe 88C, or ls lL a prob ouLslde Lhe 8M causlng Lhe problem?
1o deLermlne Lhls, look aL reLlculocyLe cL. lf Lhe 8M was Lhe prob, Lhen Lhe reLlculocyLe cL
would noL have an approprlaLe response. WhaL ls an approprlaLe response? ?ou would
8M 88C
puLLlng reLlculocyLes ouL premaLurely, Lherefore worklng correcLly Lo correcL Lhe anemla.
1herefore, lL Lells wheLher Lhe 8M ls respondlng approprlaLely or noL. lf you have blood
loss rlghL now, do noL expecL reLlculocyLe cL Lo be elevaLed ln 24 hrs, lL Lakes aL leasL 3-7
days Lo geL Lhe response of maklng more reLlculocyLes (llke Lhe kldney maklng blcarb,
whlch Lakes a few days (3-4) Lo make). lf noLhlng ls wrong wlLh Lhe 8M, Lhen lL should hosL
a normal reLlculocyLe response, lf Lhere ls someLhlng wrong, wlll noL have a normal
response (lmp b/c mlghL declde wheLher you have Lo do a 8M exam or noL). 1herefore, lf
you have a normal reLlculocyLe cL, do noL do a 8M exam.

Pave Lo correcL Lhe reLlculocyLe counL for Lhe degree of anemla.
Corrected ret|cu|ocyte ct = nct of the pt 4S ret|cu|ocyte ct LhaL you are glven
Lxample P vere anemla), and Lhe reLlculocyLe cL LhaL was
lnlLlally measured ls 9 (whlch ls lncreased anyLhlng over 3 ls lncreased).
1 8M
Lhe degree of anemla). 13/43 x 9 ls 3, so, when we correcL for Lhe anemla, we have 3,
Lherefore, 3 or greaLer = good response, 3 or less = bad
response, so, Lhls flgure ls saylng LhaL lL ls a reasonable response occurrlng ln Lhe pL.

Sllde of a reLlculocyLe (know whaL lL looks llke) need Lo do a speclal glemsa sLaln Lo see
Lhe black fllamenLs (whlch are 8nA fllamenLs), b/c Lhey are 8nA fllamenLs, Lhe reLlculocyLe
86

ls sLlll synLheslzlng Pb. So, ln abouL 24 hrs, 23 Lhe normal Pb ls belng synLheslzed and
need 8nA fllamenLs, cannoL see Lhese wlLhouL dolng a speclal sLaln (look llke llLLle black
worms ln Lhe 88C do noL confuse wlLh Pelnz body). AnoLher sllde uslng rlghL glemsa sLaln
of reLlculocyLe wlLh blulsh sLaln polychromasla. 1hese are younger blood cells Lhan Lhe 24
hr old reLlculocyLes. 1hey sLlll have Lhe basophllla, whlch ls noL normally presenL ln Lhe
perlpheral blood, so, when we see Lhem, lL means LhaL Lhe 8M ls really respondlng, and
pushlng even Lhe younger ones ouL. 1herefore, whenever
polychromasla -3 days before Lhey
become a maLure 88C. Why ls Lhls lmp? 8/c we have Lo make an addlLlonal correcLlon
why? When we are worklng up an anemla, we do a correcLed reL cL and wanL Lo know how
Lhe 8M ls respondlng rlghL now aL Lhls day. noL lnLeresLed abouL whaL wlll happen ln 2-3
P
Lhese guys wlll also have 8nA fllamenLs and wlll be counLed ln Lhe reL cL and lL wlll show a
-3 days b4 Lhey become a
maLure 88C) lnsLead we wanL Lhe normal guys Lhere. So, how do we facLor Lhem ouL?
ulvlde by 2. So, make Lhe flrsL correcLlon for Lhe degree of anemla (dld lL wlLh 3 ln Lhls
C8C L C8C
Lhen have Lo make an addlLlonal correcLlon by dlvldlng by 2. All
of a sudden, lL ls now 1.3 and Lhls ls noL a good reLlculocyLe response! So, when you see
q,>q-6kqq#-->----v
2.

Lxample: reLlculocyLe cannoL see wlLh rlghL glemsa sLaln, use speclal glemsa sLaln Lo see
8nA fllamenLs, and rlbosomes (look llke doLs 8ASCPlLlC S1lLlnC, seen ln lead
polsonlng).

III. S|de notes:

W C8C
8ule of 3 ls good: Pb x 3 should roughly equal Lhe PcL
Lxample: for prevlous le, had 13 PcL, Lherefore Lhe Pb was a 3

1 88C for every unlL Lransfused lncrease Lhe Pb by 1 and Lhe PcL by
3. Lxample P 88C 1
Pb ls 6 and Lhe PcL ls 18, ls LhaL an approprlaLe respons nC P
l Cl

MCC anem|a wor|dw|de = Ie def anem|a
MCC cause of Ie def (overa||) = GI b|eed
87

dD[P]]l c b|ood |oss,
MC due to GI tract b|eed.

88

IV. k8C |nd|ces MCV how blg ls Lhe cell? 8esL way Lo classlfy ls wlLh MCv (mean
S 1 88C
aperLure and slzes lL. And Lhen Lakes an average, Lhls ls Lhe besL way for classlfylng an anemla

MCv: < 80, lL ls mlcrocyLlc (lf you play odds, lLs le def)
MCv (normal): 80 -100 =, have normocyLlc anemla,
MCv above 100 = macrocyLlc (b12 or folaLe)

lf you have small and large cells (dlmorphlc pop 88C n
(Llke Lhe meL acldosls, and resp alk, buL normal pP). So, how could you have a le def
anemla and a folaLe def anemla aL Lhe same Llme? know where Lhese Lhlngs are
reabsorbed le reabsorbed ln Lhe duodenum, lolaLe ls reabsorbed ln Lhe [e[unum, and
812 ls reabsorbed ln Lhe Lermlnal lleum. So lf you have all Lhese, you have sma|| bowe| dz
(|e ce||ac dz), pL has malabsorpLlon LhaL affecLs dlff areas of Lhe bowel. Lxample: cellac
sprue (MCC malabsorpLlon) lnvolves duodenum and [e[unum, Lherefore wlll have def of
le and folaLe, and wlll have small cells and large cells. Lxample: lf lL lnvolves Lhe [e[unum
and Lermlnal lleum, you wlll have folaLe and 812 def.

V. kDW k8C D|str|but|on W|dth

1hls machlne looks aL Lhe 88C 88C
unlformly small, normal, macrocyLlc, or dlfferenL ln slze. So, Lhe 8uW deLecLs a change ln
88C . Lxample: mlcrocyLlc anemla, wlLh an
lncreased 8uW, Lhls Lells us LhaL ls mlcrocyLlc, and Lhere are dlfferenL slzed mlcrocyLlc cells.
Lxample: lf you develop mlcrocyLlc anemla overnlghL and all Lhe cells are le def, Lhe cells

mlcrocyLlc, and Lhere wlll be a slze varlaLlon plcked up by Lhe 8uW.

P C8C decreased MCV w|th an |ncreased
kDW, th|s |s Ie def anem|a (noL Lhalassemlas b/c LhaL ls geneLlc and ALL Lhe cells are
mlcrocyLlc).

Sllde wlLh hlgh 8uW has large and small cells. AnoLher sllde wlLh spherocyLe (have Loo
llLLle membrane, and Lherefore cannoL hold a blconcave dlsk - an anorexlc cell), and LargeL
cell (has Loo much membrane and Loo much Pb collecLs ln Lhere and lo -eye
an obese cell). 1argeL cells are lmp markers for alcohollcs b/c Lhey have alLered cell
membrane due Lo an alLered cholesLerol concenLraLlon of Lhe membrane and markers for
hemogloblnopaLhles (le Lhalassemlas, SCu, PbC).

89

MaLure 88C looks llke blconcave dlsk and ls Lhln ln Lhe mlddle b/c Lhere ls less Pb Lhere,
and more ls concenLraLed aL Lhe edges, Lhls ls why Lhere ls a cenLral area of pallor ln a
normal 88C when lL lylng flaL. All mlcrocyLlc anemlas have one Lhlng ln common: decreased
Pb synLhesls, wlLh less Pb, Lhe redness of Lhe cell wlLh decrease and see greaLer area of
luA SpherocyLe
sphere, nC cenLral area of pallor! (All red, no cenLral area of pallor). MlcrocyLlc anemlas all
have a ALL, blank color Lo Lhem, Lherefore, lL ls very easy Lo lu spherocyLe and mlcrocyLlc
cells wlLh hypochromla and luA of chronlc dz.
Audlo uay 3: PemaLology llle 2
VI. Normocyt|c Anem|a:

lor normocyLlc anemla, you need Lo look aL Lhe reLlculocyLe counL. llrsL, you have Lo
correcL for Lhe degree of anemla (PcL/43 x reL cL). 1hen look Lo see lf Lhere ls
polychromasla, lf Lhere ls polychromasla (Lhen dlvlde by 2), 3 or hlgher = 8M respondlng
normally, and 2 or lower = noL respondlng properly.

hys|ca| s|gns of anem|a: spoon nalls = le def (aka kelosls), rlboflavln def
allor of con[uncLlva = have 6 grams or less of Pb
almer crease works for whlLe people
le women, ofLen due Lo le def
Lead llne dlscoloraLlon ln gums due Lo lead polsonlng
neurologlc exam very lmp ln 812 def b/c Lhe posLerlor columns are knocked off and
laLeral corLlcosplnal LracL, Lherefore have proplocepLlon abnormallLles and decreased
vlbraLlon sensaLlon and bablnskl (laLeral corLlcal).

VII. M|crocyt|c anem|as

A. Ie stud|es four Ie stud|es:
1. Serum le (normal = 100, llke Lhe alveolar C
2
),
2. Serum ferrlLln. besL LesL Lhls ls a soluble, clrculaLlng form of le sLorage, lL rep Lhe
amounL of le sLored ln Lhe 8M, so, lf you had Lo plck one LesL for dx of le def, anemla of
a chronlc dz, or le overload, you would plck serum ferrlLln b/c Lhls ls Lhe besL screenlng
LesL.
3. 1l8C (LoLal le blndlng capaclLy), Lhe carrylng proLeln for le ls Lransferrln (Lrans =
LlvL8
4. saLuraLlon= serum le dlvlded by 1l8C

8. 3 ru|es:
1. 1ransferrln and Lhe 1l8C ls Lhe SAML! (8emember Lransferrln ls whaL carrles le).
90

2. 1here ls a relaLlonshlp of le sLores ln 8M wlLh Lhe Lransferrln synLheslzed ln Lhe llver.
When Lhe le sLores ln Lhe 8M are deflclenL (le le def anemla), LhaL ls Lhe slgnal for Lhe
1l8C
le def. 1herefore, low le sLores = lncreased Lransferrln synLhesls and lncreased 1l8C (an
lnverse relaLlonshlp), also, lf le sLores lncrease, Lransferrln and 1l8C wlll decrease (le le
overload hemochromaLosls, Lransfuslons)
3. saLuraLlon ls a calculaLlon = serum le/1l8C (normal serum le ls 100 and normal
1l8C - Lherefore, 1/3 of Lhe
blndlng slLes are occupled wlLh le.
1hese are Lhe Lerms and le sLudles we use, esp for mlcrocyLlc anemlas (relaLed Lo le
problems).

C. athogenes|s of m|crocyt|c anem|as
All mlcrocyLlc anemlas are mlcrocyLlc (b/c Lhey have a problem maklng Pb). When Lhe
88C P 88C
deLermlnes Lhe number of cell dlvlslons. 1herefore, lf Lhe Pb synLhesls ls decreased, lL ls
a slgnal ln Lhe marrow Lo lncrease Lhe number of mlLoses. When cells mlLoses, Lhey go
from someLhlng orlglnally blg Lo someLhlng small. So b/c of Lhe decrease ln Pb syn,
Lhere are exLra dlvlslons and Lherefore Lhe cell ls smaller.

All four groups of mlcrocyLlc anemlas have a decrease ln Pb.
Pb = heme + globln, Peme = le + proLoporphyrln, Clobln ls made by Lhe body alpha
(
We can dlspense 2 of Lhe 4 mlcrocyLlc anemlas lmmedlaLely:
Ie def l l
heme, so, no Ie = no heme = no nb

D. athogenes|s of Anem|a of chron|c dz
When we have lnflammaLlon, our bodles respond Lo lnflammaLlon as lf lL ls an lnfecLlon.
ln mlcro, bugs lncrease Lhelr reproducLlon wlLh le, Lherefore, Lhe more le Lhey have,
Lhe more Lhey reproduce. Same concepL: wlLh anemla of chronlc lnflammaLlon and
body assumes lL ls sub[ecL Lo a bacLerlal lnfecLlon, Lhe ob[ecL ls Lo keep le away from Lhe
bacLerla. Pow does lL do LhaL? lLs llke a safeLy deposlL box, and you have Lhe key le ls
normally sLored ln macrophages ln Lhe 8M Lhls ls where Lransferrln goes (Lo Lhe
l 88C l
l 8M
Lhe macrophages wlll be losL, Lherefore, Lhere ls loLs of le ln Lhe macrophages of Lhe
8M, buL cannoL geL lL ouL. Powever, Lhe good news ls LhaL you are keeplng lL away from
8 88C
Lherefore have an decrease ln Pb synLhesls. Powever, unllke le deflclency, where Lhere
91

ls no le ln Lhe macrophages of Lhe 8M, Lhere ls lLLS of le
and you cannoL geL lL ouL. So, lrrespecLlve of LhaL, your serum le ls decreased b/c lL ls
all locked ln Lhe mac l S
same mechanlsm as le def, buL for dlfferenL reasons: (1) you have no le (luA) and (2)
you have loLs of lL, buL lLs locked ln Lhe safeLy deposlL box and you cannoL geL lL so,
elLher way, you cannoL make heme and Lherefore you cannoL make hemoglobln. 1o
d|st|ngu|sh between IDA and ACDz, there are h|gh ferr|t|n |eve|s |n ACDz, whereas
there |s a h|gh 1I8C |n Ie def anem|a

L. neme synthes|s
CerLaln rxns ln blochem occur ln Lhe cyLosol, Lhe lnner mlLo membrane (ox phos), mlLo
lA 1CA Anu
(gluconeogenesls, whlch sLarLs ln Lhe mlLo and ends up ln Lhe cyLosol, urea synLhesls,
whlch sLarLs ln Lhe mlLo and goes Lo Lhe cyLosol and back lnLo Lhe mlLo, and heme syn
ln mlLo, Lhen cyLosol, and Lhen agaln ln Lhe mlLo). So, Lhere are 3 blochemlcal rxns ln
Lhe mlLo and cyLosol.

llrsL parL of heme syn (aka porphyrln syn) beglns ln Lhe mlLo. llrsL rxn ls succlnyl coA
(subsLraLe ln 1CA cycle and subsLraLe for gluconeogenesls), whlch can be puL LogeLher
wlLh glyclne (whlch ls an lnhlblLory neuroLransmlLLer of muscle, blocked by LeLanus Loxln
rhesus sardonlcus and LeLanlc conLracLlon so when glyclne ls lnhlblLed, Lhe muscles are
ln a Lonlc sLaLe k 8A1L LlMl1lnC L 8LL
blochemlcal rxn. (8LL ln cholesLerol syn = PMC CoA reducLase).

8LL ln heme synLhesls = ALA synLhase, cofacLor = pyrldoxlne. So, proLoporphyrln ls
made and goes back Lo Lhe mlLo. So you have proLoporphyrln plus le, so you have a
meLal plus proLoporphyrln. ChelaLase puLs Lhese LogeLher, so, lL ls called ferrochelaLase,
wlLh comblnes le wlLh proLoporphyrln and forms heme. Peme has a feedback
mechanlsm wlLh ALA synLhase 8LL eedback mech). So, wlLh lncreased
heme, lL wlll decrease syn of ALA synLhase, and when heme ls decreased, lL wlll lncrease
ALA synLhase syn.

I. athogenes|s of S|derob|ast|c anem|as (leasL common of Lhe mlcrocyLlc anemlas).
l 8 rocyLlc anemlas = s|derob|ast|c anem|as, Lhey have 3 causes:

1. Alcohol (slderoblasLlc anemla ls nC1 Lhe MC anemla ln alcohol, MCC of slderoblasLlc
anemla ls alcohol, MC anemla overall = ACuz, followed by folaLe def). Alcohol ls a
mlLochondrlal polson and uncouples ox phos, and damages lnner mlLo membrane,
allowlng proLons Lo go ln and draln Lhem off. Cn LM of Lhe mlLo of an alcohollc ls huge
b/c Lhey are damaged (called megamlLochondrla). 1herefore, any process LhaL occurs ln
92

Lhe mlLo ls screwed up. 1hls, Lherefore, lncludes heme synLhesls. So, le ls dellvered Lo
88C S
mosL of lL goes Lo Lhe mlLo, whlch ls 8Au news! Why? 8/c lL can geL ln, buL CAnnC1 geL
ouL. So, Lhere ls damaged mlLochondrla LhaL were damaged by alcohol, le goes ln and
now cannoL go ouL. So, Lhere wlll loLs of le caughL and le bullds up wlLhln Lhe mlLo.
MlLo ls locaLed around Lhe nucleus of an 88C ln Lhe 8M, leadlng Lo a rlnged slderoblasL.
1hls ls Lhe marker cell for slderoblasLlc anemla, also ln le overload dz wlll excess lron,
and wlll noL geL heme b/c mlLo desLroyed (so alcohol ls Lhe MCC).
93

2) C6u def pyrldoxlne def, le noL Laklng vlL 86 durlng 8x of 18. So, no vlL 86 = no
heme, and Lhe fl 8 l l
mlLo, walLlng for porphyrln, leadlng Lo rlnged slderoblasL.

3) lead polsonlng so lead leads Lo slderoblasLlc anemla. Lead ls a denaLurer. All heavy
meLals denaLure proLelns (enzymes are proLelns). L denaLure ls
ferrochelaLase P
Less of lnhlblLory effecL, buL does have a llLLle one on amlnolevullnlc acld dehydraLase.
8uL ls MCS1 commonly knocks off ferrochelaLase. So, when le comes lnLo mlLo, lL
cannoL blnd Lo proLoporphyrln Lo form heme. No heme = decreased nb = m|crocyt|c
anem|a.
Lxample: lf ferrochelaLase ls decreased/lnhlblLed, heme decreases, buL whaL happens
Lo proLoporphyrln before Lhe block? lL lncreases (used Lo be screenlng LesL of cholce for
lead polsonlng n W 8 l ACul
whaL wlll happen Lo Lhe proLoporphyrln ln Lhe mlLo? lL wlll lncrease. So, Lhey found ouL
LhaL many peo 88C -
polsonlng, and Lhen knew LhaL Lhe pLs had elLher le def or ACuz, and concluded LhaL lL
was noL a good screenlng LesL.

So, now blood lead level ls Lhe screenlng and conflrmaLory LesL for lead polsonlng, noL
88C

G. athogenes|s of 1ha|assem|as: A
1. A|pha tha|assem|as who do we see alpha Lhalassemlas ln? Aslans (lar easLern) and
alpha/beLa Lhal, C6u
def, SCuz).
1. Pb elecLrophoresls separaLes Lhlngs based on slze and charge, Lherefore you can
clearly separaLe PbA, Pbl, and PbA2 clearly on cellulose aceLaLe b/c Lhey have
dlfferenL mlgraLlons. So, Lhey fluoresce lL, and PbA, Pbl and PbA2 all seLLle down.
1hen Lhey sLaln Lhe cellulose aceLaLe Lo see how much ls Lhere. 1hen, lL produces
P P
wlll Lhey know Lhe percenL? WlLh a denslLomeLer lL converLs Lhe denslLy of Lhe
adulL (93-93). PbA2 ls 1-2, Pbl = 1. 1hese are Lhe normal, whlch are expressed
as a percenLage.

2. Alpha Lhalassemlas, auLo rec, has a problem ln maklng alpha globln chalns. uo
PbA2 and Pbl requlre PbA Lo be made? ?es. 1herefore, all wlll be equally
decreased. 1hls wlll nC1 show up on an elecLrophoresls, b/c all are equally
decreased, Lherefore, lL shows Lo be LoLally normal. 1here are four genes LhaL
94

conLrol alpha globln synLhesls. ueleLlon of one of Lhese four wlll noL cause anemla.
ueleLlon of 2 genes = problem b/c mlnlmally decreased, and Lherefore a mlld
anemla. lL ls mlcrocyLlc b/c Lhe globln parL ls decreased, meanlng you wlll geL a
P 1
alpha Lhalassemla mlnor
WlLh a Lhree gene deleLlon
hemolyLlc componenL Lo lL). 1he beLa chalns geL lrrlLaLed LhaL Lhere ls no alpha
chalns around, so Lhey from Lhelr own beLa globln chalns. So, four beLa chalns geL
LogeLher and form PbP. lf you do an elecLrophoresls, Lhere wlll be a dlfferenL resulL.
PP P P S
you can dx Lhls alpha Lhalassemla wlLh Pb elecLrophoresls (why lLs called PbP dz).
lour gene deleLlons sponLaneous aborLlons (usually, Lherefore noL usually born
allve aka hydrops feLalls). Camma chalns form LogeLher (llke Lhe beLa chalns dld
earller) and form a Pb wlLh 4 gammas, whlch ls called Pb 8arLs. 1hls wlll show up on
WhaL ls Lhe sponLaneous
aborLlon raLe ln far easL? Plgh b/c Lhls ls where alpha Lhalassemla ls mosL commonly
locaLed. 1herefore, lf Lhe lncldence of sponLaneous aborLlons ls lncreased, whaL
cancer rlsk ls lncreased? Chorlocarclnoma (lncreased hydaLldlform moles, whlch
leads Lo chorlocarclnoma). So, Lhere ls a hlgh lncldence of chorlocarclnoma ln Lhe far
easL b/c of alpha Lhalassemla. 8x uC nC1 glve le (wlll le overload Lhem). So, [usL
leave Lhem alone. (2
nd
MCC C esp wlLh lack of food).

2. 8eta tha|assem|a blacks, Creeks, lLallans. 8 (by lLself) = maklng normal beLa chalns,
8 8
chalns aL all. 8eLa Lhal ls auLo rec, and has Lo do wlLh spllclng defecLs, sLop codons. 1he
mosL severe form ls due Lo sLop codon (Lherefore LermlnaLe synLhesls of beLa chalns,
M||d tha|assem|a: sllghLly decreased beLa chalns, prob due
Lo a spllclng defecL, beLa chalns are sllghLly decreased, alpha chalns are okay, delLa
chalns are okay, gamma chalns flne (conflned Lo feLus). So, PbA wlll decrease, and delLa
wlll geL LogeLher (hence lncrease ln PbA2) and gamma chalns geL LogeLher (hence
lncrease ln Pbl). 1herefore, see a decrease ln PbA and an lncrease ln PbA2 and Pbl,
Lhls WlLL show up on elecLrophoresls. 1hls happened b/c beLa chaln ls decreased, and lL
showed a decreased PbA. lL ls [usL a mlld Lhalassemla and ls very common. So, only
way Lo dx 8eLa Lhal ls wlLh Pb elecLrophoresls. CannoL do anyLhlng abouL lL. Popefully
lL ls noL Lhe severe Lype, where noL maklng any beLa chalns aka C and
wlll noL llve pasL 30 y/o. Wlll have a consLanL Lransfuslon requlremenL, many of Lhese
pLs dle from le overload, or Pep C or mulLlple Lransfuslons or Plv.

95

MC ln beLa-delLa Lhalassemla (decreased beLa chalns and decreased delLa
W
Pbl. 1hls called heredlLary perslsLence of Pbl. no anemla, [usL domlnanL Pbl.

lor Lhalassemlas, know Lhey are geneLlc, whaL groups of people Lhey are ln, and LhaL you
uCn1 l l

96

n. Iron Def|c|ency Anem|a (IDA):
1. Causes of le def anemla look aL age brackeLs:
a) remaLurlLy everyday a baby ls noL ln uLero, lL ls loslng le (all Lhelr le sLores are
decreased, so baby musL be glven le supplemenLs).
b) newborn
can be swallowed. 1hls ls done wlLh Lhe apL LesL. MosL of blood LhaL comes ouL of
PA
P Pl MCC
dlverLlculum. 1 = MCC le def ln a newborn
M nC1 l
have bled by four years of age, and already would have known pL has lL.
c) Woman under 30 MCC le def = menorrhagla, Lherefore need Lo geL a good
mensLrual hx, due Lo anovulaLory cycles (beLween 20-40 y/o, due Lo ovulaLory cycles,
lnadequaLe luLeal phase, pregnancy relaLed bleeds, endomeLrlal polyp LhaL ls
bleedlng).
d) Men under 30 MCC le def = uu (usually duodenal ulcer).
e) Men and women over 30 MCC le def = Colon cancer

2. Lab 1esL l 1l8C l1l8C
l l l S

I. ACDz relaLed Lo lnflammaLlon. le ls locked ln safeLy deposlL box, so you have plenLy,
buL cannoL geL lL ouL
Serum le=low, 1l8C=low (hlgh le S1C8LS = decrease Lransferrln syn)
saL = low, serum ferrlLln = hlgh
1herefore, maln LesL Lo dlsLlngulsh ACuz from le def = serum lerrlLln!

I. M||d a|pha and beta tha| nC8MAL le sLudles b/c noLhlng Lo do wlLh le, buL globln
chalns.

k. S|derob|ast|c - le smear wlLhouL approprlaLe amounL of Pb ln Lhe cells, Lherefore, Lhey
are more Lhan llkely Lo be a mlcrocyLlc anemla (le def, ACuz, Lhalassemla, lead polsonlng).
Sllde: rlnged slderoblasL (only seen ln 8M, and ls sLalned wlLh russlan blue, whlch sLalns le
b/c mlLo around Lhe nucleus, all fllled up wlLh le called a rlnged slderoblasL Lhls ls
paLhognomonlc of a slderoblasLlc anemla). So lf you Lhlnk LhaL 86 ls causlng Lhe anemla,
need Lo prove lL. need Lo geL 8M, lf you Lhlnk alcohol ls Lhe cause, you have Lo prove lL.

L. Lead po|son|ng lf you suspecL lead polsonlng, [usL do a lead level (noL a 8M exam).
cells wlLh blue spoLs called basophlllc sLlppllng. uo noL need a speclal sLaln Lo see
basophlllc sLlppllng (shows up on glemsa sLaln). See blue doLs lead denaLures
97


1herefore, Lhey glve a greaL marker ln Lhe
perlpheral blood l 8nA l
we were Lalklng abouL perslsLenL rlbo = lead polsonlng. Cn x-ray eplphyses of flnger of
chlld, only heavy meLal LhaL can deposlL ln Lhe eplphysls of bone ls lead (mercury cannoL,
arsenlc canL, only lead can). 1herefore, can see deposlLs ln eplphyses. 1hls ls why Lhey
have fallure Lo grow. lf you screw up Lhe eplphyses of Lhe kld, Lhey wlll noL be able Lo grow
properly. Cllnlcal scenarlo chlld eaLlng palnL/plasLer leads Lo lead polsonlng, have severe
abdomlnal collc, prob wlLh cerebral edema, convulslons, severe mlcrocyLlc anemla, see lead
? l s can cause Lhls ls le
LableLs lngesLed ln a kld, lead, mercury). Also, Lhere ls a fallure Lo Lhrlve. Mechanlsm of
cerebral edema? 8elaLed Lo lncreased vessel permeablllLy of braln and bulldup of delLa-
lemavlnyllnlc acld. lf you block ferrochelaLase, everyLhlng dlsLal Lo Lhe block wlll lncrease
(proLoporphyrln, delLalemavlnyllnlc acld) Lhls ls Loxlc Lo neurons, leadlng Lo cerebral
edema.

Lxample: guy aL an auLomoblle shop, complalns of abdomlnal collc and dlarrhea. 1hls ls
lead polsonlng b/c exposure Lo baLLerles. ln planLs, Lhere ls exposure Lo lnclneraLlon of
baLLerles, and pLs are exposed Lo lead ln auLo facLorles

Lxample: moonshlne make alcohol ln old radlaLors, leads Lo lead polsonlng

Lxample: poLLery palnLer poLLery ls commonly palnLed wlLh lead based palnLs. A loL Llmes
Lhey llck Lhe Llp of Lhe brush, and leads Lo lead polsonlng.

Lxample: ln cerLaln counLry, Lhey use lead-based poLLery for dlshes, whlch leads Lo lead
polsonlng. AdulLs wlll geL Lhe neuropaLhles slapplng galL (perlneal palsy), wrlsL drop
(radlal palsy), claw hand (ulnar palsy), lead llnes ln LeeLh (usually geL wlLh collc and
dlarrhea)

M. Ie]1I8C]sat]ferr|t|n:
le def: l, h, l, l
ACuz: l, l, l, h
Alpha/beLa Lhal: n, h, h, h, do noLhlng abouL lL
Lead polsonlng (and slderoblasLlc anemlas le overload llke hemochromaLosls):
P, l, h, h (1l8C ls low b/c le sLores are hlgh!) ln le overload everyLhlng ls hlgh, 1l8C ls
LCW

Anem|a Iron 1I8C saturat|on Ierr|t|n
lron ueflclency Anemla LCW PlCP LCW LCW
98

Anemla of Chronlc ulsease LCW LCW LCW PlCP
Alpha and 8eLa 1halassemlas nL PlCP PlCP PlCP
Lead overload w/
hemochromaLosls
PlCP LCW PlCP PlCP


Audlo uay 3: PemaLology llle 3
VIII. Macrocyt|c anem|as
812 and folaLe are lnvolved ln unA synLhesls, Lherefore, lf you are 812 and/or folaLe def,
you cannoL make unA, speclflcally b/c you have a prob wlLh maklng uM (deoxyLhymldlne
monophosphaLe). 1herefore, lf you cannoL make LhaL, you cannoL maLure Lhe nucleus
(lmmaLure nuclel do noL have a loL of unA ln Lhem, buL as you make more unA, Lhe nuclel
become more maLured, and Lhe nucleus becomes smaller and more condensed). 8/c unA
cannoL be made, Lhen you have large nucleus, and all nucleaLed Lhe cells ln your body are
blg why Lhey are called MLGA|ob|ast|c anem|as. A good paLhologlsL can dx 812 and
folaLe def ln a cervlcal pap smear, when looklng aL Lhe squamous cells (cells look blg any
cell wlLh a nucleus has unA ln lL, so any cell wlLh unA wlll be blg noL [usL Lhe
hemaLopoelLlc cells LhaL are huge, ALL nucleaLed cells ln Lhe body are blg le Cl, squamous
cells)

812 aka cobalamln, 812 has cobalL ln lL. ClrculaLlng form of folaLe ls
meLhylLeLrahydrofolaLe (LeLra = four). urpose of cobalamln (812) ls Lo Lake Lhe meLhyl
1 l
unA S 8
unA l unA

Cobalamln adds a meLhyl Lo group homocysLelne, when you add a meLhyl group Lo
homocysLelne, lL becomes meLhlonlne. MeLhlonlne = aa for 1 carbon Lransfer rxns.
(MeLhyl = CP
3
). lf you are 812 or folaLe def, whaL are Lhe serum homocysLelne levels? Plgh.
WlLh a h|gh serum homocyste|ne, |t p qk ->-v uNS] - v
endothe||a| ce||s, |ead|ng to thromboses, and pred|spos|ng to MI. So, whaL ls MCC of
lncreased homocysLelne? lL ls nC1 homocysLlnurla (rare auLo rec dz), buL 812 def or folaLe
def, and folaLe ls MC Lhan 812. 1herefore, Lhe MCC of lncreased homocysLelne ls folaLe
def, and have an lncreased lncldence of Lhrombosls and Ml. 1hls ls why cardlologlsLs order
serum homocysLelne levels. ln folaLe def, no meLhyl group Lo add Lo homocysLelne (so
homocysLelne lncreases), wlLh 812 def, no meLhyl group Lo add Lo meLhlonlne Lo make
homocysLelne Lherefore meLhlonlne lncreases.

1eLrahydrofolaLe ls Lhe sLarL of Lhe cycle, and leads Lo producLlon of LhymldllaLe synLhase
Lhls ls where unA ls made. uuM ls converLed Lo uu1, maklng unA. 1herefore, Lhls
99

subsLraLe ls necessary Lo make unA. So, lL ls used ln Lhe maklng of unA by an enzyme
called dlhydrofolaLe reducLase whlch converLs oxldlzed dlhydrofolaLe Lo LeLrahydrofolaLe.
Many drugs block dlhydrofolaLe reducLase meLhoLrexaLe, 1M-SMx. 1he drugs block
unA synLhesls (le decreaslng unA synLhesls) Lhereby leadlng Lo macrocyLlc anemla. So, Lhe
funcLlonal 812 Lakes Lhe meLhyl group from LeLrahydrofolaLe and glves lL Lo homocysLelne
Lo make meLhlonlne. And LeLrahydrofolaLe wlll sLarL Lhe cycle for maklng unA.

A. 812
1. 812 8eacLlons: 812 ls humlllaLed by havlng Lo Lransfer meLhyl groups. 1hls ls an odd
requesL lA
have a problem wlLh Cuu chalne lA CA,
whlch leads Lo demenLla and proprlocepLlon loss. 812 he|ps |n odd cha|n IA
metabo||sm. 1herefore, lL ls lnvolved ln proprlonaLe meLabollsm, whlch ls meLabollsm
of an odd chaln lA. roprlonaLe forms meLhylmalonyl CoA, where 812 comes ln and
helps converL meLhylmalonyl CoA Lo succlnyl CoA, whlch can go lnLo Lhe 1CA cycle. ln
812 def, cerLaln Lhlngs wlll bulld up, such as proprlonaLe and meLhylmalonyl CoA.
MeLhylmalonyl CoA becomes meLhylmalonlyllc acld, whlch ls a senslLlve and speclflc LesL
for 812 def. So, wlLh 812 def, geL a meLhylmalonlyllc acld LesL (whlch wlll be lncreased).
8eason for neurologlcal problems ls b/c proprlonaLe meLabollsm, wlLhouL 812, cannoL
lA CoA, and Lhey bulld up, and lL screws up myelln
(cannoL syn myelln) and leads Lo demyellnaLlon of posLerlor columns, and of Lhe
laLeral corLlcosplnal LracL, along wlLh demenLla. 8/c lL ls a posLerlor column dz, you wlll
have probs wlLh proprlocepLlon, vlbraLlon, b/c you knock off Lhe laLeral corLlcal splnal
LracL, you wlll geL uMn leslons (spasLlclLy, bablnskl), and Lhen demenLla.

Wlll always Lell you LhaL you can have 812 def, and correcL Lhe anemla wlLh hlgh doses
of folaLe, buL cannoL correcL Lhe neurologlc dz. 1herefore, musL make Lhe speclflc dx.
8/c lf you Lhlnk lLs folaLe def and glve folaLe, you wlll correcL Lhe hemaLologlc problem,
buL noL Lhe neurologlcal problem, Lherefore have 812 def. So, ln d|fferent|a| of
dement|a, lnclude 812 def (alo A ?
wlLh 812, buL can have neurologlcal probs. So, wlLh demenLla, geL a 1SP level (Lo Lhrow
ouL hypoLhyroldlsm), and a 812 level Lo rule ouL 812 def b/c Lhese are 8LvL8Sl8LL
causes of demenLla.

ure vegan vs. ovo-lacLovegan: ln ovo-lacLovegan Laklng dalry producLs (whlch are
anlmal producLs), Lherefore, do noL have Lo Lake 812 supplemenLs. Powever, a pure
vegan does have Lo Lake 812 supplemenLs.

2. normal sequence of 812 absorpLlon: Pave Lo eaL meaLs or dalry producLs Lo geL 812.
1he flrsL Lhlng 812 does ls blnds Lo 8 facLor ln sallva. 8 facLor proLecLs 812 from
100

desLrucLlon by acld ln Lhe sLomach. lnLrlnslc facLor (ll) made by parleLal cells ln Lhe
body fundus, Lhey also make acld. ll ls noL desLroyed by acld, Lherefore does noL need
anyLhlng Lo proLecL lL. So Lhe 812/8 facLor complex goes lnLo Lhe duodenum, where
Lhere ls ll walLlng for lL. 8 facLor musL be cleaved off, whlch ls done wlLh enzymes from
Lhe funcLlonlng pancreas. 1hen, ll and 812 blnd Lo e/o and Lake a long Lrlp. uo noL go Lo
duodenum (le counLry), do noL go Lo llgamenLum of LrleLz ln Lhe [e[unum (folaLe
counLry), so Lhey go all Lhe way Lo Lhe Lermlnal lleum, where Lhere are recepLors for ll,
and lL ls reabsorbed. 1hls ls Lhe same place blle salLs are reabsorbed, and Lhe same
C 1 C
blle salL reabsorpLlon problems and 812 def.
3. Causes of 812 deflclency:

a) MCC 812 def = pern|c|ous anem|a, Lhls ls an auLolmmune dz wlLh desLrucLlon of
A A ll
and desLroys Lhe parleLal cells whlch are locaLed ln Lhe body and fundus. LveryLhlng
geLs desLroyed leadlng Lo an aLrophlc gasLrlLls of Lhe body and fundus. no parleLal
cells = no acld = achylorldrla, and no ll. Achylorldrla ls a ma[or predlsposlng facLor
for gasLrlc adenocarclnoma.

b) Causes of 812 def: pure vegan, chronlc pancreaLlLls seen ln alcohollcs (Lhls leads
Lo 8 8 u 8
(raresL) C C A
bacLerlal overgrowLh due Lo perlsLalsls prob and/or dlverLlcular pouches and/or
sL W
bacLerla love 812 and blle salLs wlLh bacLerlal overgrowLh. All of Lhese wlll lead Lo
812 deflclency.

8. Io|ate
lolaLe ls seen ln anlmal and planL producLs, Lherefore noL seen ln vegans. lolaLe has
many pharm Lles (le dlhydrofolaLe reducLase W
polygluLamaLe form, meanlng you cannoL reabsorb lL ln Lhe [e[unum, Lherefore lL has Lo
be converLed Lo a monogluLamaLe form. lnLesLlnal con[ugase (ln Lhe small lnLesLlne) ls
responslble for Lhls. What drug b|ocks |ntest|na| con[ugase? henyto|n. So, lf Lhey ask
abouL pL on henyLoln, wlLh macrocyLlc anemla, hypersegmenLed neuLrophlls,
neurologlcal effecLs are nC1 presenL Lherefore folaLe def (b/c Lhere are no
neurologlcal problems, Lhls r/o b12 def.) now you have monogluLamaLe, whlch ls
absorbed ln Lhe [e[unum. 1here are 2 Lhlngs LhaL lnhlblL lLs absorpLlon: (1) blrLh conLrol
and (2) alcohol (MCC fo|ate def = a|coho||sm). WlLh 812, have 6-9 year supply ln llver,
Lherefore lLs uncommon Lo geL. lolaLe only has 3-4 monLh supply so, even lf you have
an excellenL dleL, you can have folaLe def lf you are Laklng one of Lhese Lwo Lhlngs.
101


Summary: clrculaLlng form of folaLe ls meLhylLeLrahydrofolaLe, and 812 Lakes Lhe folaLe off,
and glves lL Lo homocysLelne whlch becomes meLhlonlne, Lhe meLhylLeLrahydrofolaLe
becomes LeLrahydrofolaLe, and wlLh Lhe help of dlhydrofolaLe reducLase, unA ls made.

Lxample: plc wlLh hypersegmenLed neuLrophll (deflnlLlon: 3 or more lobes!).
P 8 l
A
folaLe def. 1esL for proprlocepLlon: 8homberg LesL lf you have posL column dz, prob wlLh
proprlocepLlon b/c do noL know where your [olnLs are, does noL show cerebellar aLaxla (wlll
have Lhese wlLh eyes opened Anu closed). use vlbraLlng Lunlng fork Lo see lf pL has
proprlocepLlon on Lhe malleous.

P 8M l
88C W8C
have Lo geL back lnLo Lhe slnusolds and clrculaLe Lhrough holes. 1hey geL Lhrough, and are
ln slnusolds). 1he same Lhlng occurs ln Lhe 8M Lhey have a place equlvalenL Lo Lhe cords
of bllroLh and LhaL ls where Lhey are made. 1o geL lnLo Lhe clrculaLlons, Lhey have Lo flL
Lhrough lll, narrow holes Lo geL lnLo Lhe slnusolds ln Lhe 8M and lnLo Lhe blood sLream.
SomeLhlng very blg wlll noL be able Lo geL Lhrough Lhe lll holes and lnLo Lhe slnusolds.
1 W8C 88C
LhaL cannoL geL lnLo Lhe slnusolds. So, Lhe macrophages klll Lhem all. So ln Lhe perlpheral
blood, wlll see nC1PlnC pancyLopenla, severe macrocyLlc anemla, neuLropenla,
LhrombocyLopenla whlch ls characLerlsLlc of 812 /folaLe def. (everyLhlng ln Lhe marrow ls
Loo blg and cannoL geL ouL lnLo Lhe clrculaLlon).

L0u>>u&8? 8 W 8
and we wanL Lo know whaL caused lL. SLeps for schllllng LesL: Clve radloacLlve 812 by
mouLh, Lhey Lhen collecL Lhe 24 hr urlne Lo see lf any comes ouL ln Lhe urlne and noLhlng
comes ouL, Lherefore prove LhaL Lhey have a problem absorblng 812.

1
sL
sLep: glve radloacLlve 812 and ll, collecL urlne for 24 hrs, and plles ln Lhe urlne =
ernlclous anemla, b/c added whaL was mlsslng (ll), lf LxCLuuL
pernlclous anemla.

S

2
nd
sLep: glve 10 days worLh of broad specLrum anLlbloLlc, pL comes back and agaln you
glve Lhem radloacLlve 812, see plles of radloacLlve 812 ln Lhe urlne, whaL ls dx? 8acLerlal
overgrowLh b/c knocked off Lhe bugs eaLlng 812
102


S

3
rd
sLep: pancreaLlc exLracL, swallow pllls, Lhen glve radloacLlve 812, 24 hrs laLer, see
whaL happens, lf Lhere ls radloacLlvlLy ln urlne, pL has chronlc pancreaLlLls.

l C

Summary:
lf 812 malabsorpLlon was correcLed by addlng ll, pL has pernlclous anemla
lf 812 correcLed by addlng an anLlbloLlc, pL has bacLerlal overgrowLh
lf 812 ls correcLed by addlng pancreaLlc exLracL, pL has chronlc pancreaLlLls.

103

Ik. Normocyt|c anem|as
When you do Lhe correcLlons for Lhe anemla and look for polychromasla, lf correcLlon ls
less Lhan 2, lL ls a bad response (8M noL respondlng correcLly). llrsL Lwo Lhlngs you see:
early luA and ACuz remember LhaL you have Lo have a normocyLlc anemla flrsL Lo
u 1
need Lo geL a
ferrlLln level.

luA goes Lhrough dlff sLages: flrsL Lhlng LhaL happens decreased ferrlLln, Lhen le
1l8C l
le sLudles are A8nC8MAL before you have anemla. 1hen you geL mlld normocyLlc anemla,
and evenLually mlcrocyLlc anemla.

A. Causes:
1. 8lood loss less Lhan a week = normocyLlc anemla, no lncrease ln reL response b/c
noLhlng wrong wlLh Lhe 8M, and noL enough Llme (need 3- 8M
so, afLer one week, would geL an approprlaLe response.
2. AplasLlc anemla no marrow, lf LhaL ls Lrue, Lhe perlpheral blood wlll show
pancyLopenla (all hemaLopoeLlc cells are desLroyed ln Lhe marrow), have normocyLlc
anemla, LhrombocyLopenla, and neuLropenla.
3. MC known C = drugs: chloramphenlcal used ln rocky mLn spoLLed fever,
lndomeLhacln, phenylbuLazone, and Lhyrold relaLed drugs
4. 2
nd
MCC = lnfecLlons esp. Pep C (wlpes ouL everyLhlng), aplasla of 88C = parvovlrus
3. 8adlaLlon and mallgnancy
6. Larly luA and ACuz (need Lo have serum ferrlLln levels)
7. Mechanlsm of normocyLlc anemla wlLh less Lhen 2 reL cL renal fallure, and
decreased LC (can be glven exogenously) decreased ln hep 8, C, and Plv. ALhleLes
LC 88C C
2
dellvery Lo body

8. Mechan|sms of hemo|ys|s 2 ways to k||| an k8C:
normocyLlc anemlas wlLh correcLlve reL cL abouL 3:

1. LxLravascularly (ouLslde of Lhe 8v).
1hey are kllled by macrophages, usually ln cords of bllroLh ln Lhe spleen, someLlmes ln
llver slnusolds. Lvery 88C musL go Lo Lhe cords of bllroLh a few Llmes per day and geL
examlned by a macrophage lf Lhe cell plcked up an lgC or C3b, lL ls marked for
desLrucLlon vla phagocyLosls b/c Lhe macrophage has recepLors for lgC and C3b. lf you
lC C abnormal shape: le
sphere wlll noL be able Lo flL Lhrough a 2 mlcron hole Lo geL Lo Lhe slnusolds
Lherefore, spherocyLes are removed exLravascularly b/c Lhey cannoL geL ouL, slckle cells
104

cannoL geL ouL elLher b/c Lhey have a bad shape. AnoLher reason for Lhelr desLrucLlon ls
a plece of nucleus, whaL ls
Lhls called? Powell [olly body, macrophage wlll geL rld of lL.
1here are auLolmmune hemolyLlc anemlas, and can be due Lo lgC or C3b on Lhe surface
of Lhe 88C, or exLravascular hemolyLlc anemlas ls where you have abnormal shape (le
sphere, Slckle cell wlll noL make lL ouL of Lhe spleen b/c removed by macrophages).

Lnd producL of phagocyLoslng an 88C: uncon[ugaLed blllrubln. When Lhe 88C ls broken
down, you have hemoglobln, and Lhere ls an enzyme LhaL spllLs heme from globln and
1, Lakes Lhe heme,
spllLs lL open, and saves Lhe le. now you have proLoporphyrln, and splL lL ouL, end resulL
ls uncon[ugaLed blllrubln ln Lhe macrophage wlLhln Lhe spleen. 1hen, Lhe macrophage
splLs ouL Lhe uncon[ugaLed blllrubln lnLo blood sLream (whlch
uncon[ugaLed). 1he uncon[ugaLed blllrubln Lhen blnds albumln and goes Lo Lhe llver and
ls con[ugaLed. So, whaL cllnlcal flndlng wlll you see ln pLs wlLh exLravascular hemolyLlc
anemla? !aundlce. uoes LhaL blllrubln geL lnLo Lhe urlne? no. Why? 2 reasons: (1) Llpld
soluble and (2) 8ound Lo albumln (albumln does noL geL lnLo Lhe urlne) so you are


2. lnLravascular (wlLhln Lhe 8v)
lnLravascular ls less common meanlng LhaL you dle wlLhln Lhe 8v. Pow does LhaL
happen? ?ou dle wlLhln Lhe vessel lf you bump lnLo someLhlng. Lxample: congenlLal
blcuspld aorLlc valve wlLh calclum Lhere lf you bump lnLo LhaL, you would damage
yourself and dle. Lxample: lf you have lgM on Lhe surface of Lhe 88C (lgM ls Lhe mosL
poLenL acLlvaLor of Lhe complemenL sysLem), Lhls wlll go from 1-9, meanlng LhaL lL wlll
slL on Lhe 88C, acLlvaLe Lhe complemenL and dles lnLravascularly, so, anyLhlng LhaL ls
lgM medlaLed = lnLravascular hemolysls. So, whaL wlll you release lnLo Lhe bloodsLream
88C P u by
l S
ls released when Lhere ls lnLravascular hemolysls haptog|ob|n (aka sulclde proLeln
b/c forms complex wlLh Pb and ls phagocyLosed by Lhe macrophage), Lherefore glvlng
llfe Lo reLrleve Lhe Pb, Lherefore ln pLs wlLh lnLravascular hemolysls, Lhe hapLoglobln
levels decrease. ls lL posslble Lo geL [aun ?
phagocyLoslng. lnLravascular hemolysls: hemogloblnurla, and low hapLoglobln levels

3. Summary:
LxLravascular = macrophages remove = uncon[ blllrubln ls Lhe end producL = [aundlce
ls Lhe cllnlcal manlfesLaLlon
lnLravascular = Pb ln urlne, decreased hapLoglobln

105

C. Intr|ns|c vs. Lxtr|ns|c nemo|yt|c anem|a:
1. lnLrlnslc someLhlng wrong wlLh 88C, causlng lL Lo hemolyze: such as no specLrln, or
noL decay acceleraLlng facLor Lo neuLrallze complemenL, no C6u enzyme ln penLose
phosphaLe shunL, or abnormal Pb (le PbS). 1herefore, someLhlng wrong lnslde Lhe Pb
molecule, causlng lL Lo hemolyze.

2. LxLrlnslc noLhlng wrong wlLh Lhe 88C, [usL aL Lhe wrong place aL Lhe wrong Llme, le
lL [usL happened Lo smash lnLo Lhe calclfled valve (noLhlng was wrong wlLh lL, unLll lL hlL
Lhe valve). 1hen lL wlll be dreadlng golng Lo Lhe cords of bllroLh wlLh desLroy lL b/c lL has
been marked wlLh lgC and C3b for phagocyLosls.

D. Someth|ng |ntr|ns|ca||y wrong w|th the k8C caus|ng |t to hemo|yze
wrong wlLh Lhe 8M (buL someLhlng lnLrlnslcally wrong wlLh Lhe 88C), and Lhe correcLlve reL
cL ls greaLer Lhan 3.
MAD MC lnLrlnslc probs
Membrane defecL (spherocyLosls, paroxysmal nocLurnal hemogloblnurla), Abnormal
Pb (SC LralL uz),
Deflclency of enzyme (C6u def).

1. Membrane Defects:
(a) Spherocytos|s: do no see a cenLral area of pallor Lherefore musL be a spherocyLe
and musL be removed exLravascularly. Cllnlcally manlfesL wlLh [aundlce from
uncon[ugaLed blllrubln. SpecLrln defecL and Au dz, splenomegaly always seen over a
perlod of Llme. Callbladder (C8) dz ls common b/c Lhere ls a loL more uncon[ugaLed
blllrubln presenLed Lo Lhe llver and more con[ugaLlon ls occurrlng and more blllrubln
ls ln Lhe blle Lhan usual. So, whenever you supersaLuraLe anyLhlng LhaL ls a llquld, you
run Lhe rlsk of formlng a sLone, lf you supersaLuraLe urlne wlLh Ca, you run Lhe rlsk of
geLLlng a Ca sLone, lf you supersaLuraLe blle wlLh cholesLerol, you wlll geL a
cholesLerol sLone, lf you supersaLuraLe wlLh blllrubln, you wlll geL a Ca-blllrublnaLe
sLone. 1herefore, pLs have C8 dz relaLed Lo gallsLone dz and Lhen do a C8C wlLh
normocyLlc anemla and a correcLed reL cL LhaL ls elevaLed, and see congen|ta|
spherocytos|s. W e dlagnosLlc LesL? CsmoLlc fraglllLy 88C
88C Lherefore have an
lncreased osmoLlc fraglllLy).
8x: splenecLomy (need Lo remove organ LhaL ls removlng Lhem Lhey wlll sLlll be
spherocyLes and wlll noL be able Lo form a blconcave dlsk).

(b) aroxysma| Nocturna| nemog|ob|nur|a = defecL ln decay acceleraLlng facLor. So
when we sleep, we have a mlld resp acldosls b/c we breaLhe slowly (lf you have
obsLrucLlve sleep apnea, Lhe acldosls ls worse). When you have acldosls LhaL
106

ALL
88Cs, W8Cs, and plaLeleLs all have complemenL slLLlng on lL. 1here ls no complemenL
desLrucLlon of Lhese cells b/c ln our membranes we have delay acceleraLlng facLor.
1

hemogloblnurla, neuLropenla and LhrombocyLopenla. So, lf you are mlsslng decay
acceleraLlng facLor, Lhe complemenL wlll be acLlvaLed and goes from C1-9, leadlng Lo
lnLravascular hemolysls. 1hlnk abouL Lhe name (paroxysmal nocLurnal
hemogloblnurla): occurs aL nlghL, and when you wake up ln Lhe mornlng, you pee ouL
hemoglobln. So, when you do a C8C, noL only have a severe anemla, buL also a
neuLropenla and a LhrombocyLopenla: pancyLopenla).

2. Abnorma| nb: S|ck|e Ce|| 1ra|t]Dz
WlLh slckle cell LralL, Lhere ls nC anemla and nC slckled cells ln Lhe perlpheral blood.
?ou can have slckled cells ln a cerLaln parL of your body ln Lhe renal medulla wlLhln
Lhe perlLubular caplllarles (decreased C
2
Lenslon), buL noL ln Lhe perlpheral blood.
1hls ls b/c ln SCuz, Lhe amounL of slckled Pb ln Lhe 88C deLermlnes wheLher lL slckles
or noL. Mag|c # = 60, lf you have 60 or more, PbS can sponLaneously slckle.
Cxygen Lenslon ln Lhe blood also deLermlnes wheLher a cell wlll slckle or noL. AL
lower C
2
Lenslons, cells are more llkely Lo slckle. 1hls ls an auLo rec dz, meanlng LhaL

23 compleLe normal, 30 heLerozygous asympLomaLlc carrler, 23 compleLe dz
(same wlLh cysLlc flbrosls).

SC 1ra|t vs. SCDz:
(a) ln s|ck|e ce|| tra|t, black lndlvldual wlLh normal L and normal C8C, buL
mlcroscoplc hemaLurla, Lhe flrsL sLep ls slckle cell screen b/c mlcroscoplc
hemaLurla ls ALWA?S abnormal and musL be worked up buL ln blacks = 1/8 people
have Lhe LralL. So, SC LralL ls whaL you are Lhlnklng of, noL renal sLones, or lgA
glomerulonephrlLls, buL ls SC LralL normally.

(b) SCDz 2 Lhlngs are happenlng: PemolyLlc anemla (usually exLravascular)
can be very severe and commonly requlres a Lransfuslon and Cccluslon of small
8v by Lhe slckled cells (blockage of clrculaLlon) lead Lo vasoocluslve crlsls, and
Lhls lschemla leads Lo paln. 1herefore, Lhey are palnful crlsls (occur anywhere ln
Lhe body lungs, llver, spleen, 8M, hands/feeL (bacLullLls)). Cver Llme, lL leads Lo
damage of organs kldneys, spleen auLolnfarcLed (auLosplenecLomy) ln flrsL 10
88C
auLosplenecLomy around age 19 (spleen wlll be Lhe slze of a Lhumb). AfLer 2
years, lL ls nonfuncLlonal s
107

worklng. Pow wlll you know whaL LhaL has happened? Powell !olly body (88C
wlLh a plece of nucleus LhaL should noL be ln Lhe spleen lf Lhe spleen were
worklng, a flxed macrophage would have Laken care of lL). 1hls occurs aL abouL 2
yrs of age. 1hls ls forLunaLe b/c Lhls ls abouL Lhe age where you can geL
pneumovax. WlLh a nonfuncLlonal spleen whaL lnfecLlon ls guaranLeed? SLrep
pneumonlae sepsls.
MCC death |n ch||d w|th SCDz = strep pneumon|ae seps|s.
1hey Lry Lo cover wlLh anLlbloLlcs and pneumovax pneumovax can be glven aL

Powell [olly bodles). Sllde wlLh Powell [olly body and sllde wlLh slckled cells, Lhen
wlll a l P
been removed lf Lhe spleen ls funcLlonal.

When do Lhey geL Lhelr flrsL slckle cell crlsls? When llLLle klds geLs palnful hands,
and are swollen up (called bacLullLls) does noL occur aL blrLh, b/c Pbl lnhlblLs
slckllng and newborns ln newborns, 70- 88C Pl l SCu -
88C Pl PS
A Pl 88C
broken down and replaced, Lhe Pbl decreases and PbS lncreases, and by 6-9
monLhs of age, Lhere ls a hlgh enough concenLraLlon Lo lnduce slckllng and Lhelr
S -9
monLhs b/c Pbl lnhlblLs Lhe slckllng.
8one lnfarcLlons occur from slckllng Lhe 8M.
CsLeomyellLls Lhese pLs are suscepLlble Lo osLeomyellLls from salmonella due Lo
a dysfuncLlonal spleen. Salmonella ls desLroyed by macrophages. 1he spleen
normally fllLers ouL salmonella, buL ls dysfuncLlonal. MCC osLeomyellLls ls sLaph,
buL MCC ln SCuz pL = salmonella.

WhaL drug ls used Lo decrease Lhe lncldence of vasoocluslve crlses? Pydroxyurea.
Pow does lL work? lL lncreases Pbl synLhesls.

3. Def|c|ency of enzyme: G6D def|c|ency
C6u def ls x-llnked recesslve.

M ku W
Lhe Lwo x- Cu L-nyhan syndrome
(lnvolves purlne meLabollsm wlLh menLal reLardaLlon, self muLllaLlon, lncreased urlc
acld, def of PC81).

108

Clucose 6 phosphaLe has several funcLlons: (1) Lo make gluLaLhlone, (2) Lo make
rlbose 3 carbon sugars for maklng unA, and (3) Lo make glycogen from C6
(converLed Lo C1, uu-glucose and glycogen).

key: wlLh Lhls enzyme, we can make nAuP, whlch ls Lhe maln facLor for maklng
anabollc Lypes of blochemlcal rxn (le sLerold synLhesls). nAuP wlll reduce oxldlzed
gluLaLhlone Lo gluLaLhlone, lLs [ob ls Lo neuLrallze peroxlde Lo waLer. Whlch vlLamln
caLalyzes Lhls rxn? 8lboflavln. Whlch enzyme helps gluLaLhlone neuLrallze peroxlde?
CluLaLhlone peroxldase. Whlch Lrace meLal ls lnvolved? Selenlum. Lvery llvlng cell
makes peroxlde as an end producL, Lherefore every cell musL a way Lo handle lL.
CaLalase prese 88C l
ln peroxlsomes. CLher way Lo neuLrallze peroxlde ls wlLh gluLaLhlone (only Lhlng
88C S
enzyme, Lhere l S 88C
why would LhaL occur? 8/c lf you had an lnfecLlon, or lf you Look an oxldlzlng drug (le
sulfa drug, nlLryl drug), whlch wlll lead Lo a loL more peroxlde lylng around. eroxlde
wlll noL be able Lo be neuLrallzed lf you are deflclenL ln caLalase. So, whaL wlll
happen ls Lhe peroxlde wlll affecL Lhe Pb. 1he peroxlde wlll cause Lhe Pb Lo clump
and form Pelnz bodles (Pb clumped up LogeLher). Wlll also affecL Lhe 88C
membrane b/c lL damages Lhe membrane so much LhaL Lhe prlmary mechanlsm of
desLrucLlon ls lnLravascular. LlLLle elemenL ls exLravascular, buL mosLly lnLravascular.
lL ls preclplLaLed by lnfecLlons and/or drugs. 2 MC drugs: 1) pr|maqu|ne mlsslonary
goL malarla, recelved a drug, and 2-3 days laLer Lhe goL hemogloblnurla, chllls, and a
hemolyLlc anemla (Lhls ls prlmaqulne lnduced hemolysls). 2) Dapsone ls used ln
LreaLlng leprosy, every person wlLh leprosy ls glven a screen for C6u def b/c of Lhe
hlgh lncldence of produclng hemolysls. See Lhls dz ln Lhe same populaLlon as 8eLa
Lhal blacks, Creeks, lLallans. Sllde: smear wlLh acLlvely hemolyzlng blood cells
ne|nz bod|es when lL goes lnLo Lhe cords of bllroLh, Lhe macrophage wlll Lake a blg
blLe ouL of lL and someLlmes, ls a small blLe ouL of Lhe membrane, and Lhe cell goes
(88C wlLh llLLle membrane).
need Lo do speclal sLalns Lo lu Pelnz bodles. ln Creeks or lLallans wlLh severe forms
of C6u def, Lhey can eaL fava beans whlch can preclplLaLe an eplsode (aka favlsm).
Dx when you have an acuLe hemolyLlc eplsode, Lhe lasL Lhlng you wanL Lo geL a
dlagnosls ls Lo geL an enzyme assay. Why? 8/c Lhe only cells LhaL are hemolyzed are
Lhe ones mlsslng Lhe enzymes. 1he ones LhaL have Lhe enzyme are sLlll gonna be
Lhere, so you have a normal assay. So, nLvL8 use enzyme assays for acLlve
hemolysls. need Lo speclal sLaln Lo lu Lhe Pelnz body. When Lhe hemolyLlc eplsode
e wlLh a C6u assay. W||| get a
quest|on on G6D def|c|ency, e|ther dapsone re|ated or pr|maqu|ne re|ated.

109

k. Auto|mmune hemo|yt|c anem|as

Warm reacLlng anLlbodles are lgC and cold reacLlng ls lgM
MC auLolmmune hemolyLlc anemla = warm, MCC of lL = Lupus

When you have auLolmmune dz ln your famlly, you have cerLaln PLA Lypes LhaL predlspose
you Lo LhaL auLolmmune dz. 1herefore, you should noL be surprlsed lf you have one
S
auLolmmune hemolyLlc anemla, auLolmmune LhrombocyLopenla, auLolmmune
neuLropenla, and auLolmmune lymphopenla.

l MCC
le pernlclous anemla, vlLlllgo, auLolmmune desLrucLlon of
melanocyLes). So, lf you have one auLolmmune dz, you are llkely Lo have oLhers (le lf you
have a hemolyLlc prob, lL ls prob auLolmmune relaLed).
1hls ls b/c of Lhe PLA relaLlonshlp. 1herefore, lf you have a famlly LhaL has an auLolmmune
dz, whaL would be Lhe slngle besL screenlng LesL Lo use? PLA (le lf Lhey have Lhe PLA Lype
speclflc for lupus PLA 1 PLA
see lf pL ls predlsposed Lo someLhlng.

MCC auto|mmune anem|a = Lupus, lL has lgC and C3b on Lhe surface of Lhe 88C, so lL wlll
be removed by Lhe macrophage. 1hls ls an exLravascular hemolyLlc anemla. Pow do we
lC C A u C : deLecL ul8LC1L?
Lhe pre lC C 88C lndlrecL coombs ls whaL Lhe
women geL, when Lhey are pregnanL and Lhey do an Ab screen on you (looklng for any klnd
of Ab), so, when you look for Ab ln Lhe serum (nC1 on 88C, on SL8uM), Lhls ls an lndlrecL
Coombs. 1herefore, anoLher name for Lhe lndlrecL Coombs = Ab screen, wlLh dlrecL
coombs lC C Su8lACL 88C
88C
So, the test of cho|ce |f you susp-q>---SI

A. Drug |nduced auto|mmune hemo|yt|c anem|as:
1here are 3 Lypes of drug lnduced hemolyLlc anemla (2
nd
MCC auLolmmune hemolyLlc
anemla = drug lnduced, MCC = lupus)
1. CN mechanlsm: Lhe bpo group of Cn aLLaches Lo 88C (lll plece of Cn ls
aLLached on 88C membrane). 1hls ls bad lf an lgC Ab develops agalnsL lL b/c lf lL
does, Lhan Lhe lgC aLLaches Lo Lhe bpo group, goes Lo Lhe spleen and ls removed
exLravascularly, Lhls ls an le of Lype ll P?
Lxample: pL on Cn develops a rash whaL Lype of P?? 1ype l. Lxample: L on Cn
develops a hemolyLlc anemla whaL Lype of P?? 1ype II
110


2. Methy|dopa aka aldomeL. use: anLl-P1n for pregnanL woman (oLher anLl-P1n
used ln pregnancy = hydralazlne). MeLhyldopa and hydralazlne have compllcaLlons
meLhyldopa can cause a hemolyLlc anemla, hydralazlne can lead Lo drug-lnduced
lupus (2
nd
Lo procalnamlde for drug lnduced lupus). MeLhyldopa works dlfferenLly
from Cn: meLhyldopa messes wlLh 8h Ag on surface of 88C and alLers Lhem. 1hey
lC A 8 A CWn 8 A S
Lhe drug ls noL slLLlng on Lhe membrane, lL [usL causes formaLlon of IgG A
aLLach Lo 88C Lo have macrophage klll lL whaL Lype of P? ls Lhls? 1ype II.
1herefore, meLhyldopa and Cn are Lype ll for hemolyLlc anemla.

3. u|n|d|ne
Culnldlne acLs as Lhe hapLen, and Lhe IgM Ab aLLaches, so, Lhe drug and lgM are
aLLached LogeLher, clrculaLlng ln Lhe bloodsLream. 1hls ls a dlfferenL n type III,
and wlll dle a dlfferenL way, b/c Lhls ls lgM. When lgM sees Lhe lmmune complex, lL
wlll slL lL, and acLlvaLe Lhe classlcal paLhway 1-9, leadlng Lo lnLravascular hemolysls,
and hapLoglobln wlll be decreased, and ln Lhe urlne, Pb wlll be presenL.
kI. M|croang|opath|c hemo|yt|c anem|a

88C schlsLocyLes (schlsLo means spllL). MCC chron|c |ntravascu|ar
hemo|ys|s = aort|c stenos|s, ln Lhls dz, Lhe cells hlL someLhlng, Lherefore have lnLravascular
hemolysls, Pb ln Lhe urlne and hapLoglobln ls down. 1hls ls a chronlc lnLravascular
hemolysls, and you wlll be loslng a loL of Pb ln Lhe urlne, whaL does Pb have aLLached Lo lL?
le, so whaL ls anoLher poLenLlal anemla you can geL from Lhese pLs? le def anemla.
Lxample: wlll descrlbe aorLlc sLenosls (sysLollc e[ecLlon murmur, 2
nd
lCS, radlaLes Lo Lhe
caroLlds, S4, lncreased on explraLlon, promlnenL Ml), and Lhey have Lhe followlng C8C
flndlngs: MCv 88C Lhls ls a mlcroanglopaLhlc
hemolyLlc anemla relaLed Lo aorLlc sLenosls.

CLher causes of schlsLocyLes: ulC (lll flbrln sLrands spllL 88Cs rlghL aparL b/c 88C ls very
fraglle), LhromboLlc LhrombocyLopenlc purpura, PuS see schlsLocyLes. When you have
plaLeleL plugs everywhere ln Lhe body, Lhe 88Cs are banglng lnLo Lhese Lhlngs causlng
schlsLocyLes and mlcroanglopaLhlc hemolyLlc anemla. Lxample
88C monly, you go pee and see Pb
ln lL, Lo prevenL, use baLhroom b4.

AnoLher cause of hemolyLlc anemla: ma|ar|a fa|c|parum b/c you have mulLlple rlng forms
(gameLocyLe (comma shaped and rlnged form). lL produces a hemolyLlc anemla, whlch
correlaLes wlLh Lhe fever. 1he fever occurs when Lhe cells rupLure (Lhe hemolyLlc anemla).

111

CnA1Lk 6. nLMA1CLCG: W8C

I. Non-neop|ast|c Lympho|d ro||ferat|ons:
A. Neutroph||s when you have acuLe lnflammaLlon = le appendlclLls, neuLrophlllc
leukocyLosls, lefL shlfL, Loxlc granulaLlon, and leukamold rxn. Leukamold rxn means LhaL
u W
causes leukamold rxns? 18 and sepsls. ?ou see greaLer Lhan 30-30,000 cells ln Lhe
blood. klds geL Lhese a loL (le oLlLls medla). AdulL wlLh oLlLls med = 12,000, klds wlLh
30,000 (exaggeraLed). Lxample: ertussus whoop|ng cough |ymphocytos|s (60,000)
ALL
LhrombocyLopenla, kld comes ln pale, coughlng. LymphocyLes are maLure and are
LoLally normal. LymphocyLosls w/ vlral lnfecLlon or wlLh perLussus.

ln atyp|ca| |ymphocytos|s
when presenLed Lo and Ag. l A
W aLyplcal
lymphocyLe, Lhe absoluLe flrsL Lhlng LhaL pops lnLo Lhe mlnd ls: mononuc|eo|os|s L8V.
CLher dz LhaL are seen wlLh large, beauLlfully sLalnlng blulsh cells: CMv, Loxoplasmosls,
any cause of vlral hepaLlLls, phenyLoln. L8v ls called Lhe klsslng dz b/c Lhe vlrus holds up
ln Lhe sallvary glands. L8v affecLs 8 cells and Cu 21. Mono causes vlremla, generallzed
palnful lymphadenopaLhy, very commonly geL exudaLlve LonsllllLls, [aundlce (hardly ever
seen), lncreased Lransamlnases (off Lhe charL), and spleen enlargemenL and can rupLure.
1
usually for 6-8 weeks. Also causes macrocyLlc anemla vla lnhlblLlng lnLesLlnal
con[ugase).
Audlo uay 3: PemaLology llle 3

Lxample: Lhe boards wlll glve you a classlc hx of mono, and ask whlch LesLs you run, buL
monospoL LesL ls noL on Lhe cholces b/c Lh
anLlbodles (heLero = dlff, phlle = lovlng). P A - 88C A (or
anLl- A C
always have lL and wlll have 3-4 recurrences over your llfeLlme le reacLlvaLlon conslsLs
of swollen glands, very Llred, eLc. L8v llves ln 8 cells, Lhe aLyplcal lymphs ln mono are 1
cells reacLlng agalnsL Lhe lnfecLed 8 cells.

8. Monocyte = klng of chronlc lnflammaLlon, Lherefore expecL monocyLosls ln pLs wlLh
chronlc lnfecLlons C

S|de Note: creaLlne glves energy b/c lL blnds Lo phosphaLe, and LhaL ls Lhe phosphaLe you geL
from maklng A1 so whaL serum LesL ls markedly elevaLed ln someone Laklng creaLlne for
112

Lhelr muscles? CreaLlnlne! 8/c Lhe end producL of creaLlne meLabollsm ls CreaLlnlne. 1he 8un
ls normal ln Lhls person. WorLhy board quesLlon.
C. Los|noph|||a
?ou would see eoslnophllla ln Pay fever, rash ln pL wlLh Cn, sLrongololdes
roLozoa lnfecLlons uCLS nC1 produce eoslnophllla, Lherefore lL rules ouL amablasls
(plnworm), glardla, and malarla. Cnly lnvaslve helmlnLhes produces eoslnophllla. AdulL
ascarlasls does nC1 cause eoslnophllla b/c all Lhey do ls ob
lnvaslve larvae form crosses lnLo Lhe lungs LhaL causes eoslnophllla. So anyLhlng LhaL ls
1ype l P? causes eoslnophllla, proLozoa do noL cause eoslnophllla, ascarlasls, and
plnworms do nC1 cause eoslnophllla (all oLhers le whlpworms do b/c Lhey lnvade).

II. Mye|opro||ferat|ve Dz: o|ycythem|a lncreased 88C cL, lncreased Pb and PcL
ulfference beLween serum na and LoLal body na? yes. Serum na ls mllllequavalenLs per
llLer of plasma, LoLal body na ls mllllllLers per kg body wL (Lhe LoLal amounL you have).
Slmllarly: k8C mass 88C L ln body wL
k8C ct 88C , Lherefore lLs how many you have ln a cerLaln
volume of blood. Why ls Lhls a blg deal? Lxample: wenL runnlng and vol depleLed 88C cL
88C
(b/c you depleLed Lhe plasma volume), buL whaL would Lhe 88C mass be? normal (noL
88C S 88C ke|at|ve
= decrease ln plasma vol causlng an lncrease ln 88C cL, buL Lhe 88C mass ls normal.
Abso|ute lncrease ls approprlaLe or lnapproprlaLe?
When would lL be approprlaLe? S 88C Llssue hypoxla, so, any source of Llssue
hypoxla would be an approprlaLe response. Lxample: lf you have lung dz, hypoxemla,
CCu, hlgh alLlLude W
1 aLe polycyLhemla.
So, Lhere are Lwo Lhlngs Lo Lhlnk abouL wlLh |ncreased k8C mass: po|ycythem|a rub|vera,
whlch ls an le of a sLem cell prollferaLlve dz of Lhe 8M, meanlng LhaL Lhe sLem cells are
dlcLaLors, and noLhlng keeps Lhem ln check a neoplasLlc dz, Lhey can become leukemlas.
So, lL would be lnapproprlaLe Lo have normal blood gases and no evldence of Llssue hypoxla
and have an lncrease ln 88C mass. 2) 1umor or cyst w|th an excess product|on of LC:
renal adenocarclnoma maklng LC, causlng an lncrease ln 88C mass Lhls ls lnapproprlaLe
b/c a Lumor ls lnapproprlaLely maklng lL.

ln summary: polycyLhemla ls relaLlve or absoluLe. 8elaLlve means LhaL you [usL losL plasma
vol (le from runnlng) wlLh 88C cL lncreased, and mass ls normal. AbsoluLe lncrease: ls lL
approprlaLe or lnapproprlaLe? ApproprlaLe anyLhlng LhaL ls a hypoxlc sLlmulus for LC
l LC
ecLoplcally maklng LC from a Lumor or cysL or you have polycyLhemla rublvera (a
myeloprollferaLlve dz).
113

III. Mye|opro||ferat|ve dz neoplasLlc sLem cell dz LhaL has losL all regulaLlon and noLhlng can

1. olycyLhemla rublvera
2. CML (only leukemla ln Lhls caLegory)
3. Agnogenlc myelold meLaplasla 8M ls replaced by flbrous Llssue
4. LssenLlal LhrombocyLhemla where a sLem cell LhaL makes plaLeleLs goes crazy and
make 1 mllllon, 600 plaLeleLs for mlcrollLer,
3. MyelodysplasLlc syndrome

A. o|ycythem|a rub|vera: P

1. nyperv|scos|ty 18
4
). WlLh
polycyLhemla, lL wlll have an lncreased reslsLance and 18 wlll go up, lL wlll predlspose
Lo Lhrombosls, whlch kllls you Lhrombosls of anyLhlng le dural slnuses, MCC 8udd
chlarl = hepaLlc veln Lhrombosls, coronary arLery, SMv, anyLhlng can be Lhrombosed b/c
blood slugglng around and Lhls ls why phleboLomy ls done. hleboLomy ls performed Lo
make you le def Lhey wanL Lo make you le def why? lf you make Lhem le def, b/c
Lhe 88C

2. nypovo|em|a only polycyLhemla LhaL has an lncrease ln plasma volume LhaL
maLches Lhe lncrease ln 88C mass, none of Lhe oLher causes have an lncrease ln plasma
vol (Lhese are measured wlLh radloacLlve Lechnlques). So, lL ls very rare Lo see an
lncrease ln plasma vol wlLh polycyLhemla, excepL for Lhls case. Why? MyeloprollferaLlve

boLh lncrease LogeLher over Llme.

3. n|stam|nem|a 88C W8C
and basophlls. Lxample: Classlc hx: pL Lakes a shower and geLs lLchy all over body
Lhls ls a Llp off for polycyLhemla rublvera why? MasL cells and basophlls are locaLed ln
Lhe skln and LemperaLure changes can degranulaLe masL cells, causlng a release of
hlsLamlne, leadlng Lo generallzed lLchlng (very few Lhlngs cause generallzed lLchlng
blle salL deposlLlon ln Lhe skln ln pLs wlLh obsLrucLlve [aundlce, and pLs wlLh masL cell
degranulaLlon), face ls red looklng, Loo b/c of hlsLamlne b/c vasodllaLaLlon, leadlng Lo
mlgralne-llke headaches.

4. nyperur|cema b/c nucleaLed hemaLopoeLlc cells are elevaLed, Lhey Lhen dle, and
Lhe nuclel have purlnes ln Lhem. 1he purlnes wlll go lnLo purlne meLabollsm and
become urlc acld. Lxample: pL on chemoLherapy musL also be puL on allupurlnol Lo
prevenL uraLe nephropaLhy and prevenL renal fallure from urlc acld. (allupurlnol blocks
xanLhane ox W
114

nucleaLed cells are kllled and Lhe Lubules are fllled wlLh urlc acld, leadlng Lo renal fallure.
MusL puL Lhem on allupurlnol. 1hls called Lumor lysls syndrome. 1he same Lhlng occurs
ln polycyLhemla rublvera b/c Lhere ls an lncrease ln number of cells LhaL evenLually dle
and you run Lhe rlsk of hyperurlcemla.
8. k8C mass]p|asma vo|]C2 sat]LC

olycyLhemla rublvera h,h,n (lnapproprlaLe), low (have Loo much C2 b/c you have
plles of 88C LC 1 C
conLenL=1.34 * Pb * C2 saL +pC2

CCu, LeLralogy of falloL, hlgh alL P n L P
respondlng Lo hypoxla)

8enal adenocarclnoma, hepaLocellar carclnoma, any cysL (renal, esp. le hydronephrosls,
P, n, n, P (even wlLh normal gas sLudles b/c ecLoplcally produced)

8elaLlve olycyLhemla n, L, n, n

IV. Leukem|as
1hey are a mallgnancy of Lhe 8M and meLs anywhere lL wanLs.

A. Genera| character|st|cs of Leukem|a, therefore, w||| a|ways have:
C
2. Abnormal cells ln Lhe perlpheral blood 8LAS1S (myeloblasLs, lymphoblasLs,
monoblasLs, megakaryoblasLs) so some abnormal blasLs are ln Lhe perlpheral blood
3. 8/c lL ls arlslng ln Lhe 8M, wlll always crowd ouL Lhe normal hemaLopoeLlc cells, and
wlll ALWA?S have an anemla, usually normocyLlc
4. 1hrombocyLopenla b/c crowdlng ouL Lhe normal megakaryocyLes from maklng
plaLeleLs
3. usually an lncrease ln W8Cs cL wlLh abnormal cells presenL
6. AcuLe vs. chronlc uo a bone marrow LesL and look aL blasLs lf blasLs are <30, Lhls
ls chronlc, lf Lhe blasLs ls >30, lL ls acuLe. 1herefore Lhe blasL cL Lells lf lLs acuLe vs
chronlc

8. Age brackets: know age brackets
0-14 = ALL
13-39 = AML myeloblasL wlLh Auer rods ln perlpheral blood
40-39 AML, CML (separaLe wlLh 8M AML wlLh >30 and CML wlLh <30, 9, 22, hllly

60+ = CLL
115

!"#$%&'())#)&*+&,-(#'&.('/)&00#$1#(.&#2#"33#
!""#.&4&'()-5&/#4$46>>
7*6#789#-6#,&60#6$#):,;<#4$/&0=>#
116

C. D|fferent 1ypes of Leukem|a:
Lxample: perlpheral smear of 49 y/o, 130,000 W8C cL, 1 myeloblasL ln perlpheral
blood and 8M, generallzed nonLender lymphadenopaLhy, hepaLosplenomegaly,
LhrombocyLopenla, and normal anemla dx? CML (look aL age brackeL and blasLs). 1o
prove, geL 9, 22 sLudy (abl proLooncogene wlLh nonreacLor Lyroslne klnase acLlvlLy and
goes from 9 Lo 22 and fuses wlLh Lhe clusLer fuslon gene). LA leukocyLe alkallne
phosphaLase sLaln can also be used. Look aL whlch neuLrophlls Lake lL up maLure
neuLrophlls all have LA ln Lhem, neoplasLlc neuLrophlls do noL why? 8/c Lhey are
neoplasLlc. So, lf no sLaln, know lLs neoplasLlc (normal cells Lake up sLaln). Called a LA
score CML S LA
always low.

Lxample: Lear drop cell b/c Lhere was a dlcLaLor ln 8M, and cells have Lo move Lo Lhe
spleen, so Lhere ls a mlgraLlon of hemaLopoeLlc cells from Lhe 8M Lo Lhe spleen. When
you Lake up hemaLopoesls anywhere oLher Lhan Lhe bone marrow, Lhls ls called
exLramedullary hemaLopoesls. So, Lhe spleen ln huge esp. ln aLherogenlc myelold
meLaplasla. Some of Lhe megakaryocyLes go back Lo Lhe marrow Lo lay down collagen,
and megakaryocyLes go back. llbrosls of Lhe 8M occurs (used Lo be called myeloflbrosls
meLaplasla). So, noL everyone lefL Lhe 8M, and sLay ln Lhe flbroLlc marrow. lor Lhem Lo
geL Lo Lhe spleen, Lhey have Lo work Lhelr way Lhrough sLrands of flbroLlc Llssue, ofLen
Llmes damaglng Lhelr membrane, leadlng Lo Lear drop cells (so, lL geLs passed Lhe
flbrous Llssue and geLLlng lnLo Lhe slnusolds, Lhey are Lear drop cells ln
Lhe perlpheral blood). So, pL wlLh huge spleen, wlLh Lear drop cells atherogen|c
mye|o|d metap|as|a.

Lxample: Loo many plaLeleLs essent|a| thrombocythem|a (makes Loo many plaLeleLs)

Lxample: 4 y/o pL LhaL presenLs wlLh sLernal Lenderness, fever, generallzed nonLender
lymphadenopaLhy, hepaLosplenomegaly, normocyLlc anemla, 30,000 W8C counL many
of whlch had an abnormal appearance cells. WhaL ls Lhe dx? ALL (acute |ymphob|ast|c
|eukem|a. MC cancer ln klds, Lhe mosL common Lype ls: common ALL Ag 8 cell leukemla.
Cu10+, calla+ Ag 8- ALL

Lxample: 63 y/o, normal crlLerla, smudge cells and normocyLlc anemla. 1hey also have
hypogammagloblnemla b/c Lhey are neoplasLlc 8 cells and cannoL change Lo plasma
cells Lo make lgs. 1herefore, MCC deaLh ln CLL = lnfecLlon relaLed Lo
hypogammagloblnemla. WhaL ls Lhe ux? CLL

Lxample: 62 y/o, normal crlLerla, speclal sLaln of 18A (LarLraLe reslsLanL acld
phosphaLase sLaln) ha|ry ce|| |eukem|a (know Lhe 18A sLaln)
117


Lxample: 33 y/o pL, wlLh normal crlLerla, wlLh 30,000 abnormal W8Cs and Auer rods
(abnormal lysosomes), 70 blasL cells ln Lhe 8M. WhaL ls Lhe ux? AML. know whaL
Auer rods look llke, know Lhe leukemla LhaL lnfllLraLes gums (acuLe monocyLlc anemla
M3), and acuLe progranulocyLlc anemla (M3) Lhey always have ulC, has a LranslocaLlon
13,17. 8x = reLlnolc acld (vlL A causes blasLs Lo maLure lnLo b9 cells).

V. Lymph nodes

A. Genera| Character|st|cs:
1. alnful vs palnless: lymphadenopaLhy LhaL ls palnful ls noL mallgnanL, mean LhaL you
have lnflammaLlon causlng lL (does noL always mean lnfecLlon) you are sLreLchlng Lhe
W
non-Lender, Lhlnk mallgnanL, elLher (1) meLs or 2) prlmary lymphoma orlglnaLlng from lL.
Always Lell lf palnful/less.

2. Locallzed vs. generallzed lymphadenopaLhy: Locallzed (le exudaLlve LonsllllLls goes Lo
local nodes, breasL cancer goes Lo local nodes. Cenerallzed (sysLemlc dz le Plv, L8v,
Lupus).

3. Lxamples:
(a) 8ruLo germlnal folllcle absenL: 8-cell
(b) ulCeorge syndrome paraLrabeculae messed up: 1-cell counLry
(c) PlsLlocyLes (Pan shculler ChrlsLlan/leLLerman sleve dz) lnvolves slnuses
(d) SClu (adenlne deamlnase def) 8 and 1 cell deflclency, Lherefore no germlnal
folllcle and no paraLrabeculae buL wlll have slnuses.
(e) 8eacLlve lymphadenopaLhy: Macrophage Lakes Ag, and presenLs Lo germlnal
A

8. Non-Uv#-S>q
lolllcular lymphoma = MC non-P L 8-cell, LranslocaLlon 14,18, and
apopLosls gene knocked off, so Lhe cells are lmmorLal.

What 2 t|ssues are res|stant to |nvas|on by cancer ce||s? Cart||age and e|ast|c t|ssue

Lxample: 8urk|tts, caused L8v, 1ranslocaLlon 8,14, myc oncogenes, sLarry sky normal
macrophages looklng llke sky aL nlghL, #3 MCC cancer ln klds, can cure, MC lymphoma ln
klds, usually ln Lhe abdomen (le payers paLches, paraorLlc lymph nodes, also buL rarely
ln Lhe [aw, or LesLes)

118

Lxample: plaque llke leslons, no LeeLh, noL a fungal lnfecLlon acLually Lhe
lnflammaLory cells are really neoplasLlc, so Lhe helper 1 cell ln mycos|s fungo|des ls
1 l
Sezary cell syndrome whlch ls seen ln perlpheral blood (mallgn helper 1 cell LhaL ls ln
perlpheral blood, ln mycosls fungoldes)

Lxample: kld wlLh LM of eczemaLous rash all over generallzed nonLender
hepaLosplenomegaly, , LM of monomorphlc cells whlch were Cu 1+ cells hlsLlocyLosls
x (|etterman s|eve dz) (blrbeck granules, look llke Lennls rackeL
closLrldlum LeLanl whlch has a spore also looks llke a Lennls rackeL)

Audlo day 3: hemaLology flle 6

alnful lymphadenopaLhy = some Lype of lnflammaLory condlLlon, noL mallgnanL

alnless lymphadenopaLhy = mallgnancy: MC mallgnancy of lymph node = meLasLasls
MC prlmary cancer of lymph node =
P 8 1
off apopLosls gene and Lhe cell ls lmmorLal).

C. Uv#-S l P
sweaLs, and wL loss (usually 18 unless proven oLherwlse). lL ls usually locallzed, nonLender
lymphadenopaLhy. Cn mlcro: Lhe mallgnanL cell ls 8eld SLelnberg cells, 8S cells owl eyes -
common on boards (also glardla, CMv, ashoff nodule ln rheumaLlc fever). Less # = beLLer
prognosls, more = worse

1he mosL lmporLanL one ls Nodu|ar Sc|eros|s: MC = nodular sclerosls, seen ln women, lL
ls nodular (hence Lhe name), and
and non-palnful node). ?ou would see lL ln a woman wlLh lymph node lnvolvemenL ln 2
places: 1) anLerlor medlasLlnum and 2) somewhere above Lhe dlaphragm- le Lhe cervlcal
nodes, superclavlcular nodes, neck. 1hls comblnaLlon of mass ln neck and anLerlor
medlasLlnum = nodular sclerosls. ?ou would see 8S cells on mlcro.

2. 1erms: poly and monoclonal (Lhls wlll help Lo undersLand Lhe dlff from mulLlple
myeloma and oLher Lhlngs LhaL lncrease gamma globulln p). Cn serum proLeln
elecLrophoresls, albumln mlgraLes Lhe farLhesL b/c lL has Lhe mosL neg charge, whereas
gamma globulln [usL slLs Lhere.

(a) olyclonal
clones of plasma cells b/c Lhe gamma globulln reglon ls where Lhe gamma globullns
119

1 -a-
globulln. 1herefore, on elecLrophoresls, you see a llLLle peak, Lhls ls an lncrease ln lgC
lC Lhls makes sense b/c for chronlc lnflammaLlon, Lhe
maln lg ls lgC, and for acuLe lnflammaLlon Lhe maln lg ls lgM. So, ln chronlc
C uC lC
whlch wlll show a large dlffuse elevaLlon (a nlce round mLn). 1hls ls called polyclonal
gammopaLhy b/c many benlgn plasma cells are maklng lgC. olyclonal gammopaLhy
always means benlgn and chronlc lnflammaLlon. Wlll noL have polyclonal
gammopaLhy wlLh acuLe lnflammaLlon (le acuLe appendlclLls), Lhls noL any rlse ln Lhe
gamma gobulln reglon for acuLe lnflammaLlon Lhe maln lg ls lgM for acuLe.

(b) Monoclonal l
l S ak, Lhls
mallgnancy of plasma cells. Meanwhlle, all oLher plasma cells are
suppressed by lmmunologlc mechanlsms. 1he mallgnanL clone makes lLs own lg,
mosL of Lhe Llme lL ls an lgC mallgnancy. 1hey are maklng many llghL chalns and geL
lnLo Lhe urlne Lhese are called 8ence !ones proLelns. Monoclonal usually means
mallgnancy and always means mulLlple myeloma.

(c) eaks (ln order): albumln, alpha 1, alpha 2, beLa, gamma have

a pL 23 y/o, non-smoker, had emphysema of Lhe lower lungs, no alpha 1 peak whaL
ls ux? Alpha 1 anLlLrypsln def.

VI. |asma Ce|| D|sorders:
A. Mu|t|p|e Mye|oma (MM)
MM 8M l
usually seen ln people over 30, a llLLle more common ln women. 1he mosL common
form ls lg kappa, whlch ls abundanL. lasma cells have lL-1 (aka osLeoclasL acLlvaLlng
facLor), Lhls ls why you see loLs of lyLlc leslons ln Lhe skull or bones. 1he lyLlc reglons
lyLlc reglons are fuzzy and noL
sharply cuL). Whlle ln MM leslons have a flne, sharp (cookle cuLLer cuL) border, b/c lL-1
acLlvaLes osLeoclasLs, leadlng Lo Lhe punched ouL leslons.

Lxample: lf Lhere was a lyLlc leslon ln Lhe rlbs and pL coughed, whaL would poLenLlally
happen? aLhologlc fracLures and Lhese are exLremely common.

Lxample: elderly woman coughs and develops severe paln you see lyLlc leslon of Lhe
rlb, so whaL does Lhe pL have? MulLlple myeloma

120

know whaL plasma cell looks llke has brlghL blue cyLoplasm and nucleus ls eccenLrally
locaLed (around Lhe nucleus are clear areas presenL). Cn LM, wlll see layer and layers of
8L8 8nA
MusL know whaL plasma cell looks llke on LM and glemsa sLaln. Summary of mulLlple
myeloma lyLlc leslons, 8ence !ones proLelns, and seen ln elderly pLs.

1. Amy|o|dos|s: ls a cllnlcal characLerlsLlc of MM
Amylold on LM ls a non-branchlng, llnear compound wlLh a hole on Lhe cenLer of lL.
1hey always ask a quesLlon on amyloldosls b/c lL ends up ln Lhe dlfferenLlal dx for
mulLl- A
ls LhaL many oLher dlfferenL proLelns can be Lransformed/converLed lnLo Lhls unlque
proLeln le pre-albumln,
x calclLonln (Lumor marker for medullary carclnoma of Lhe Lhyrold),
x llghL chalns ln MM, and
x Lrlsomy 21. ln 1 u
amylold, and lf you have Lhree of Lhese, you wlll make more beLa amylold
proLeln. And beLa amylold proLeln ls Loxlc Lo neurons, so, lf you have Lrlsomy
21 are maklng more beLa amylold proLeln, Lhen you wlll be loslng more
neurons b/c you are loslng more of Lhls proLeln LhaL ls Loxlc Lo neurons. 1hls ls
why Lhey always ask Lhe quesLlon abouL a pL dylng aL forLy and on auLopsy,
you see aLrophy of Lhe braln and lL reveals senlle plaques ln fronLal and
Lemporal lobes, and wlll ask whaL pL had u A
A u rom 1 of 2 Lhlngs: elLher from (1)
endocardlal cushlon defecLs whlch leads Lo hearL defecLs and an ASu (ln
vSu A chromosome 21 ls
maklng Loo much beLa amylold proLeln L A
has downs syndrome. 8eLa amylold ls mosL lmporLanL proLeln.

<aa7(\>8?
1wo dlfferenL cells LhaL Lhey llke Lo ask quesLlons abouL.
1. Caucher dz: Lhere ls a macrophage wlLh a crlnkled paper llke appearance ln Lhe
cyLoplasm. 1here are lysosomes fllled wlLh glucocerebroslde, Lherefore pL has Caucher
dz l

2. nlemann-lck dz: bubbly cyLoplasm, severe menLal reLardaLlon, bulldup of
sphlngomyelln ln Lhe lysosomes, Lherefore Lhe pL has nlemann-lck dz, mlsslng
sphlngomyellnase.

3. u: only glycogen sLorage dz LhaL has lysosomal sLorage =
glycogen sLorage dz LhaL ls lysosomal b/c Lhey are mlsslng an enzyme Lo break glycogen
121

down ln Lhe lysosomes. Pow does pL dle? ule from cardlac fallure b/c excess deposlLlon
of normal glycogen ln Lhe hearL.

Summary: bubbly cyLoplasm = nlemann-
lysosomal sLorage dz

122

CnA1Lk 6: nLMCDNAMIC DSIUNC1ICN

I. 1hrombogenes|s: 1he Coagu|at|on System

PemosLasls 8v l
noL prevenLed, Lhe pL elLher has ulC, LhromboLlc LhrombocyLopenlc purpura (11), or PuS,
S 8v
vessels lnclude arLerloles, venules, and caplllarles, whlle small alrways lnclude Lermlnal
bronchloles, resp bronchloles, alveolar ducL, and alveolus].

7 L/0&? o\>+ 8/c we have coagulaLlon facLors such as: heparln, Cl
2,
roLeln C and S, and Llssue plasmlnogen acLlvaLor. So all of Lhese Lhlngs are used Lo
prevenL llLLle cloLs occurrlng ln our small blood vessels.

1. Peparln (a CAC, a mucopolysaccharlde). lL ls normally found ln Lhe body and helps
prevenL formaLlon of cloLs. Pow does heparln work? lL LnPAnCLS anLlLhrombln lll.
AnLlLhrombln lll ls made ln Lhe Llver (llke all oLher proLelns). 1herefore, heparln geLs Lhe
credlL for anLlcoagulaLlng you, buL lLs anLlLhrombln lll does all Lhe work. AnLlLhrombln lll
neuLrallzes mosL of Lhe coagulaLlon facLors. So, we have a llLLle blL of heparln ln our
small vessels, whlch prevenLs cloLLlng from occurrlng.
2. Cl
2
, prosLacyclln, made from endoLhellal cells, a vasodllaLor. When Lhe vessel ls
vasodll
more dlfflculL for a Lhrombus Lo sLlck b/c lL blows away so fasL.
1herefore, vasodllaLaLlon ls anLagonlsLlc Lo formlng Lhrombl ln anyLhlng b/c everyLhlng
ls movlng Loo qulckly. Cl
2
also prevenLs plaLeleL aggregaLlon.

3. roLeln C and S are vlL k dependenL facLors (as are facLors 2, 7, 9, 10). luncLlons of
proLeln C and S: Lhey lnAC1lvA1L (le neuLrallze or geL rld of) Lwo Lhlngs facLors 3 and
8. 1hey acLually lnhlblL facLors 3 and 8 ln our body. 1hls ls lnLeresLlng b/c anLlLhrombln
lll cannoL lnhlblL Lhese. AnLlLhrombln lll can only lnhlblL serlne proLeases, and lacLor 3
and 8 are noL serlne proLeases.

4. L-A (Llssue plasmlnogen acLlvaLor) Lhls ls whaL we use Lo dlssolve a cloL ln a pL wlLh
coronary Lhrombosls lL acLlvaLes plasmlnogen, whlch produces plasmln. lasmln
baslcally eaLs everyLhlng ln slLe.

8. Def|c|ency |n any of the ant|coagu|ants: So, lf we are def ln any of Lhese Lhlngs (heparln,
Cl
2
, proLeln C and S, and L-A), cloLs would form. ln oLher words pL wlll be Lhrombogenlc.

123

Why are pLs on blrLh conLrol Lhrombogenlc? 8/c lL lncreases Lhe synLhesls of 3 and 8,
lncreases syn of flbrlnogen, and lnhlblLs anLlLhrombln lll. So, blrLh conLrol pllls are
blocklng heparln by lnhlblLlng A1lll. 1herefore, Lhe esLrogen of Lhe plll ls Lhrombogenlc,
Lhereby asslsLlng ln Lhe formaLlon of cloLs. ueadly duo: woman on blrLh conLrol and
smoklng = bad, smoklng ls Lhrombogenlc b/c lL damages endoLhellal cells (so boLh are
Lhrombogenlc).

C. Iormat|on of a stab|e c|ot
lor example: a pL ls shavlng and cuL hlmself. Pow do we sLop bleedlng when you cuL a
small 8v (noL Lalklng abouL muscular arLerles need Lo plug LhaL)
ln[ury/cuL/damage of a small vessel (le arLerlole, venule, caplllary. WhaL wlll sLop Lhe
bleedlng? 1o deLermlne Lhls we use bleedlng Llme as le: bleedlng Llme ls used Lo
evaluaLe plaLeleL funcLlon.

Lxample: lf pL has hemophllla A and has no facLor 8, Lhe pL wlll sLlll have a nC8MAL
bleedlng Llme b/c bleedlng Llme has nC1PlnC Lo do wlLh coagulaLlon facLors.

8leedlng Llme ls purely a LA1LLL1 Lhlng.

1. Pow do Lhey perform Lhe LesL?
CuL Lhe pL (lnfllcL wound), sLarL sLop waLch, and dab wound every LhlrLy sec, when Lhe
normally lL ls 7-9 mlns.

2. 1he paLhway of bleedlng Llme: When Lhe vessel ls cuL, Llssue LhromboplasLln ls
released (whlch acLlvaLes Lhe exLrlnslc coagulaLlon sysLem, buL has noLhlng Lo do wlLh
bleedlng Llme). 1he cuL exposes collagen and of course Pageman facLor (facLor 12) ls
acLlvaLed by Lhe exposed collagen, hence Lhe lnLrlnslc paLhway ls acLlvaLed, buL Lhls has
noLhlng Lo do wlLh bleedlng Llme, elLher. LndoLhellal cells and megakaryocyLes make an
adheslon producL (a Lype of glue) whose speclal purpose ls Lo sLlck Lo plaLeleLs vWl.
vWl ls parL of Lhe facLor 8 molecule and ls made ln 2 places megakaryocyLes ln Lhe 8M
W y a llLLle
blL of glue wlLh Lhem ln Lhelr granules. Also, plaLeleLs are made ln Lhe endoLhellal cells.
S 8v Wl
vWl whlch ls baslcally an adheslon molecule ([usL llke neuLrophlls had recepLors for
Lhe endoLhellal cell made by Lhe endoLhellal cell). lf neuLrophlls cannoL sLlck Lo venules,
Lhen Lhey cannoL geL ouL Lo klll bugs. Same concepL here plaLeleLs have Lo sLlck Lo
before Lhey can do Lhelr Lhlng so vWl ls Lhe adheslon molecule LhaL allows Lhem Lo do
LhaL. So, now Lhe plaLeleL sLlcks called plaLeleL adheslon. When Lhe plaLeleL sLlcks, lL
causes Lhe plaLeleL Lo release chemlcals mosL lmp chemlcal ls Au Lhls ls a poLenL
aggregaLlng agenL, and causes plaLeleLs Lo sLlck LogeLher. 1hey sLarL Lo help form a
124

Lhrombus Lo begln Lo sLop Lhe bleedlng. Powever Lhls ls noL enough Lo compleLe Lhe
process. So, Lhls ls called Lhe release rxn when Lhe plaLeleL sLlcks, lL causes Lhe
plaLeleL Lo release chemlcals, and Lhe mosL lmp chemlcal ls Au. When plaLeleLs come
by, Lhey wlll sLlck LogeLher (b/c of Lhe Au) and Lhe bleedlng wlll go down. 8uL sLlll noL
enough, needs anoLher chemlcal. As soon as Lhe plaLeleL has Lhe release rxn, lL sLarLs
synLheslzlng lLs own unlque subsLance 1hromboxane A
2
, plaLeleLs make lL b/c Lhey are
Lhe only cell ln Lhe body LhaL has Lhromboxane synLhase. So, lL can converL gA
2
lnLo
1xA
2
, poLenL vasoconsLrlcLor. 1hls ls lmporLanL ln sLopplng bleedlng, b/c lf you slow raLe
of blood flow, lL wlll m
geL washed away. As opposed Lo prosLacyclln, whlch ls a vasodllaLor Lhe plaLeleLs
cannoL sLlck b/c Lhe blood flow has lncreased. 1xA
2

anglna. lL L1 C
u4, and L4.
So, 1xA
2
ls a vasoconsLrlcLor, a bronchoconsLrlcLor, and a plaLeleL aggregaLor. lL puLs Lhe
flnlshlng Louches on lL and causes Lhe plaLeleLs Lo really aggregaLe, and blocks Lhe
ln[ured vessels, and bleedlng Llme has [usL ended.

3. lnLegraLlon: laLeleLs do Lwo Lhlngs (1) release rxn, where chemlcal were already
made ln lL were released so, preformed chemlcals were released and (2) lL makes lLs
own chemlcal called 1xA
2
1 MAS1 CLLLS l lL
brldged LogeLher, and pollen brldged Lhe gap. 1hls caused Lhe masL cells Lo have a
release rxn (release of preformed chemlcals: hlsLamlne, seroLonln, and eoslnophll
chemoLacLlc facLor). 1hese chemlcals Lhen sLarLed Lhe lnflammaLory rxn ln a Lype l P?
rxn. 1he masL cell released arachldonlc acld from lLs membrane and we ended up
C 1
furLhered/enhanced Lype l P? (lnflammaLory) rxns. So Lhe masL cell had a release rxn
C 1
dld: released lLs preformed chemlcals and made lLs own chemlcal: 1xA
2
.

lug ls Lemporary lL ls a bunch of plaLeleLs sLuck LogeLher and held LogeLher by
flbrlnogen, and ls enough Lo prevenL bleedlng (Lo sLop bleedlng Llme), buL lf you scraLch


4. CondlLlons LhaL arlse wlLh lncreased or decreased bleedlng Llme: LeLs screw up
bleedlng Llme:

(a) WhaL would be an obvlous mess up of bleedlng Llme? 1hrombocyLopenla:
decreased plaLeleL counL Lherefore lf you have less Lhan 90,000 plaLeleLs, you wlll
have a prolonged bleedlng Llme b/c you wlll noL have enough Lo aggregaLe. AnoLher
125

dz LhaL has a problem wlLh adheslon molecule defecL ls vW8 dz (MC geneLlc
heredlLary dz, Au)

(b) MCC prolonged bleedlng Llme = Laklng asplrln, mechanlsm? Asplrln blocks plaLeleL
CCx, noL 1xA
2
(blocked by ulpyrramldal). LndoLhellal cells have CCx, Loo, so why
CCx Cl
2
? 1he plaLeleL CCx vs Lhe
endoLhellal CCx reacLs dlfferenLly Lo asplrln. ulfferenL compounds acL dlfferenLly Lo
non- l asplrln block plaLeleL CCx more Lhan endoLhellal CCx),
cannoL neuLrallze boLh would be bad. So, asplrln ls lrreverslble and oLher nSAlus
are reverslble for 48 hrs. So, lf you Look an asplrln, lL prevenLs plaLeleLs from
aggregaLlng, and Lherefore Lhey do noL work, so lf you cuL yourself, Lhe bleedlng Llme
A 1A
work and you wlll conLlnue bleedlng.

3. ConLlnuaLlon of CloLLlng: 8ecall LhaL Lhe release of L-A whlch wlll acLlvaLe exLrlnslc
sysLem and lL also acLlvaLes Lhe Pageman facLor 12 b/c of collagen belng exposed
Lherefore Lhe lnLrlnslc sysLem ls also acLlvaLed. Lnd producL of coagulaLlon ls Lhrombln,
and Lhrombln converLs flbrlnogen lnLo flbrln. So, we have plle of plaLeleLs sLuck
LogeLher and Lhey are bound wlLh flbrlnogen. WhaL wlll happen rlghL afLer Lhe bleedlng
Llme ends? 1he acLlvaLed Lhrombln (produced by Lhe exLrlnslc and lnLrlnslc paLhways)
wlll converL Lhe flbrlnogen (whlch ls holdlng Lhe plaLeleLs LogeLher loosely) lnLo flbrln,
maklng a more sLable plaLeleL plug LhaL you are noL able Lo dlslodge. So, who wlll
remove LhaL plaLeleL plug from Lhe vessel? lasmlnlnogen, and when lL ls acLlvaLed and
plasmln are formed, plasmln wlll drlll a hole Lhrough lL and recanallze, so Lhe vessel ls
normal agaln.

D. |ate|et def|c|ency vs Coagu|at|on def|c|ency
So, wlLh bleedlng Llme, Lhe plaLeleLs (whlch are held LogeLher wlLh flbrlnogen) form a
1 sLable. When Lhe
CoagulaLlon sysLem makes Lhrombln, lL converLs flbrlnogen lnLo flbrln, maklng a sLrong
plaLeleL plug. 1hls dlfference ls very lmp b/c lL dlsLlngulshes a dlfference beLween a plaLeleL
abnormallLy vs coagulaLlon facLor deflclency

1. lf you have a plaLeleL problem, whaL wlll happen Lo bleedlng Llme? rolonged, b/c lf
Lhe pL cuLs a vessel, whaL wlll happen? lL wlll conLlnue Lo bleed (Lherefore a plaLeleL
prob). 1herefore, ln plaLeleL abnormallLles, you see bleedlng from superflclal scraLches
l
addlLlon, you mess up Lhe lnLegrlLy of small vessels when plaLeleLs are messed up,
leadlng Lo peLechla (hemorrhage only see ln a plaLeleL abnormallLy plnpolnL area of
126

hemorrhage), echymoses (purpura), eplsLaxls (nose bleed, whlch ls Lhe MC
manlfesLaLlons ln plaLeleL problem).

nCnL of Lhese manlfesLaLlons (peLechla, echymoses, eplsLaxls, and bleedlng from
superflclal scraLches) occurs ln CoagulaLlon facLor deflclency!!!

2. CoagulaLlon deflclency: Lxample: pL w/ hemophllla A def ln facLor 8, whaL ls
bleedlng Llme? normal. WhaL Lype of problems do Lhese pLs run lnLo? LA1L re-bleedlng.
Lxample: appendecLomy everyLhlng wenL flne, pL woke up, sLarLlng movlng around
and blood sLarLed comlng ouL (masslve amounLs of blood came ouL of Lhe wound and
pL bled Lo deaLh). 8/c Lhe only Lhlng LhaL was holdlng Lhe blood ln was suLures and
Lemporary hemosLaLlc plugs. lf you have a CoagulaLlon facLor def, you cannoL converL
flbrlnogen lnLo flbrln, and Lhe plaLeleLs wlll fall away, leadlng Lo laLe re-bleedlng. L ls
able Lo handle superflclal scraLches/cuLs. Powever, wlll noL hold vessel closed for Loo
long b/c laLe re-bleedlng wlll Lake place. 8esL quesLlon Lo ask Lo see lf Lhey have a
C L
says yes, 1hen ask, dld you have any problems wlLh bleedlng? nC, (Lherefore pL does
nC1 have Coag facLor def.), why? LxLracLlon of a wlsdom LooLh lmposes Lhe greaLesL
hemosLaLlc sLress on Lhe sysLem LhaL ever exlsLs, lLs even worse afLer a LhoraocLomy,
and loLs of surglcal procedures. So lf afLer exLracLlon of a wlsdom LooLh no bleedlng
occurred, Lhen Lhey have normal Coag facLors.

Lxample: lf pL had a wlsdom LooLh exLracLed, and had hemophllla A, pL had no problems
wlLh bleedlng, however, whaL ls Lhe CnL? Lhlng holdlng Lhe wound shuL? Lll Lemporary
plaLeleL plugs LhaL are held LogeLher by flbrlnogen (noL flbrln). uenLlsL Lells you Lo wash
mouLh ouL (wlLh salL or a llLLle blL of peroxlde) when you geL home, bad b/c you wlll
bleed Lo deaLh and suffocaLe on your own blood (all hemosLaLlc plugs are gone and pL
bleeds Lo deaLh). 1hls ls LA1L rebleedlng, noL from superflclal scraLches. CLher
condlLlons of coagulaLlon deflclency: Menorrhagla more of Coag def, Lhan a plaLeleL
problem, and Lhe poLenLlal for PemearLhroses: where you bleed lnLo closed spaces.

Summary: So, plaLeleL problem (eplsLaxls, echymoses, peLechla, bleedlng from superflclal
scraLches) vs coagulaLlon problem (laLe re-bleed, Menorrhagla, Cl bleeds, hemarLhroses).
1hls ls all based on knowlng whaL happens Lo small vessels.

L. 1ests for p|ate|et abnorma||t|es
1. llrsL do plaLeleL counL: lf you Look an asplrln you sLlll have a normal # of plaLeleLs, buL


2. Secondly do 8leedlng Llme assesses plaLeleL funcLlon
127


3. 1esL for vWl? 8lsLocedln cofacLor assay - lf mlsslng vWl, rlsLocedln cause
Wl

So, Lhree LesLs LhaL assess plaLeleLs: plaLeleL counL, bleedlng Llme, rlsLocedln cofacLor
assay (for vW8 uz)

Lxample: older man wlLh osLeoarLhrlLls prosLaLe was resecLlon and masslve bleeds: lf
have osLeoarLhrlLls, you have paln, and lf you have paln, you wlll be on paln medlcaLlon,
an nSAluS, and wlll glve LesL resulLs 1/11/plaLeleL counL all normal bleedlng Llme
ls longer. 8x plaLeleL pack Lransfuslon when you glve from a donor, lL WlLL work
S nSAlu worklng and lf
you have a prob durlng surgery, glve pL plaLeleLs from donor.
Audlo day 3: hemaLology flle 7
I. Lxtr|ns|c vs. Intr|ns|c system:
1. lacLors lnvolved:
LxLrlnslc = facLor 7
lnLrlnslc = facLors 12, 11, 9, 8
8oLh share Lhe same flnal common paLhway facLor 10. (WhaL ls anoLher sysLem
LhaL has a flnal common paLhway? ComplemenLwheLher by Lhe classlcal paLhway,
Lhe alLernaLe paLhway, or by Lhe MAC paLhway, all lncludes C3)
WhaL do we have lefL? 10, 3, 2 (roLhrombln), 1 (flbrlnogen) and Lhen Lhe cloL.

2. 1esLs lnvolved:

a) roLhrombln Llme (1):
LvaluaLes Lhe exLrlnslc sysLem all Lhe way down Lo Lhe formaLlon of a cloL so lL only
deals wlLh 7, 10, 3, 2, and 1. Lnd sLage of Lhe LesL ls a cloL ln Lhe LesL Lube. ln8 =
sLandardlzed way of dolng lL sLandardlzaLlon Lechnlque (same everywhere ln
world).

b) arLlal LhromboplasLln Llme (11):
LvaluaLes Lhe lnLrlnslc sysLem all Lhe way down Lo a cloL so lL deals wlLh 12, 11, 9, 8,
10, 3, 2, and 1.

Lxample: 1 ls prolonged, buL 11 ls normal, whaL ls Lhe facLor def? 7
8/c Lhe proLhrombln was prolonged, Lhls lncludes 7, 10, 3, 2, or 1. And Lhe 11 are
normal, meanlng LhaL 12, 11, 9, 8, 10, 3, 2, 1 are all normal. So Lhe only one
responslble ls 7.
128

Lxample 11 ls prolonged, buL 1 ls normal, whaL ls Lhe facLor def? lacLor 8 (play
odds). Why? lf 11 ls prolonged, lL ls 12, 11, 9, 8, 10, 3, 2, and 1 LhaL ls Lhe problem.
Powever Lhe 1 ls normal, Lherefore 7, 10, 3, 2, and 1 are normal. 1herefore, lLs one
Lhe 11 facLors (12, 11, 9, 8). We know whaL hemophllla A (nexL Lo vW8 uz) ls Lhe
MC

Lxample: whaL dld warfarln block? Lpoxlde reducLase. So, LhaL prevenLed Lhe
gamma carboxylaLlon of lacLors: 2, 7, 9, and 10. So, whaL do you follow wlLh
warfarln? 1. WhaL ls Lhe only facLor you are noL evaluaLlng Lo when you are dolng a
1 Llme for a person on warfarln? lacLor 9 b/c lLs parL of Lhe lnLrlnslc sysLem. WhaL
ls Lhe 11 ln a person on warfarln? rolonged b/c facLors 2 and 10 are vlL k
dependenL facLors ln Lhe flnal common paLhway. Powever, 1 does a beLLer [ob ln

proLhrombln Llme. So, boLh 1 and 11 are prolonged when you are on warfarln, buL
1 ls beLLer dlagnosLlc Lool.

Lxample: whaL do you follow heparln Lherapy wlLh? 11 (evaluaLes Lhe lnLrlnslc
paLhway). lacLors LhaL anLlLhrombln lll knocks off: 12, 11, 7, 10, 2, 1 are all
neuLrallzed by anLlLhrombln lll. So, wlLh pL on heparln, 11 ls prolonged, whaL ls Lhe
1 l 11
facLors anLlLhrombln lll lnvolved wlLh)

So, 8C1P 1 and 11 are prolonged lf on warfarln or heparln, however, lL Lurns ouL
LhaL 11 ls beLLer aL evaluaLlng heparln and 1 ls beLLer for warfarln.

II. I|br|no|yt|c system: |asm|n

lasmln leaves crumbs lLs breaks down Lhlngs (flbrlnogen, flbrln, coagulaLlon facLors)
Lhlnk flbrlnoL?1lC sysLem. When lL breaks down a cloL, Lhere are many pleces (le flbrln) lefL
around, whlch are flbrln degradaLlon producLs.

WhaL ls Lhe slngle besL screenlng LesL for ulC? D-d|mers (beLLer answer) or flbrln spllL
producLs. WhaL plasmln does ls breaks Lhlngs aparL, leavlng crumbs behlnd and you have
degradaLlon producLs. u dlmers are Lhe absoluLe besL LesL for ulC (dl- means 2). When you
form a flbrln cloL, facLor 13 (flbrln sLablllzlng facLor) makes Lhe cloL sLronger. Pow do you
sLablllze sLrands? Llnk Lhem by puLLlng connecLlons beLween Lhem Lo make Lhem sLronger
(Lhls ls whaL facLor 13 does). So, how do you make collagen sLronger? 8y, llnklng Lhem Lo
lncrease Lhe Lenslle sLrengLh (facLor 13 wlll puL a crossbrldge ln flbrln). WhaL u-dlmer ls
deLecLlng are only Lhose flbrln facLors LhaL have a llnk (le when Lhere are Lwo of Lhem held
129

LogeLher, Lhls whaL Lhe LesL plcks up). WhaL does Lhls absoluLely prove? 1haL Lhere ls a flbrln
cloL. uo you see Lhls ln ulC? ?es.

Lxample: Would you see lL lf you broke aparL a plaLeleL Lhrombus ln a coronary arLery?
(8emember a plaLeleL Lhrombus ls a bunch of plaLeleLs held LogeLher by flbrln). So, whaL
would Lhe u dlmer assay be lf you broke aparL LhaL cloL? lncreased, you would see lncreased u
dlmers and would see Lhe llLLle flbrln sLrands held LogeLher by cross llnklng. 1hey ofLen do
LhaL Lo see lf you have recanallzed or lf you goL rld of your Lhrombus.

Lxample: lL ls ofLen also seen wlLh a pulmonary embolus, b/c lf you have a pulmonary
embolus, one LesL ls a u dlmer b/c you wlll form a cloL LhaL wlll acLlvaLe Lhe flbrlnolyLlc sysLem,
and lL wlll Lry Lo sLarL breaklng lL down, and Lhere wlll be a release of u dlmers. Slngle besL LesL
for ulC. Cood LesL for plcklng up pulmonary embolus, along wlLh venLllaLlon/perfuslon scans.
LxcellenL LesL Lo see lf you have reperfuslon afLer glven L-A b/c lL proves LhaL lf u dlmers were
presenL, a flbrln cloL musL be presenL (flbrln was Lhere so lL proves lL).

III. Vesse| abnorma||t|es

A. Sen||e purpura: Seen on Lhe back of hands of an old person Lhey hlL Lhlngs and geL
senlle purpura, vessels geL unsLable as you geL older and subcuLaneous Llssue Lhlns. When
8v called senlle purpura, an age
dependenL flndlng. Cnly presenL ln places LhaL normally hlL Lhlngs, back of Lhe hands and
Lhe shlns. Lxample: Mom was puL ln old age home and Lhe chlldren were gonna sue Lhe old
age home for abuse. uo Lhe chlldren have a case? no, b/c lL has noLhlng Lo do wlLh abuse
and ls an age dependenL flndlng. Lxample: now lf Lhey also saw echymoses on buLLocks
and back, Lhls ls noL a normal place Lo geL Lrauma relaLed Lo [usL bumplng lnLo Lhlngs LhaL
would be abuse. S
hand. Lveryone wlll geL Lhls, everyone, no one ls exempL.

8. Cs|er Weber kendu Dz aka hered|tary te|ang|ectas|as: Many of Lhese pLs have chronlc
le def anemla, relaLed Lo perslsLenL Cl bleeds. ?ou can make Lhe dx wlLh L of Lhe pL. 1he
pL wlll have small red doLs called LelanglecLaslas and lf you look on Lhe llps and Longue you
wlll see LelanglecLaslas, and lf you do endoscopy, you wlll see Lhe llLLle red doLs LhroughouL
Lhe Cl LracL. WhaL does Lhls pL have? Csler Weber 8endu uz aka heredlLary LelanglecLaslas.
lL ls Lhe MC geneLlc vascular dz. 1herefore, you can see why you geL chronlc le def and
bleeds b/c Lhe LelanglecLaslas wlll rupLure. lL ls klnd of llke Lhe anglodysplasla of Lhe skln

S C W 8
scurvy.

130

IV. |ate|et Abnorma||t|es

llndlngs of plaLeleL problems: all have a problem ln maklng a hemosLaLlc plug, eplsLaxls (MC),
peLechla, echymoses, and bleedlng from superflclal scraLches/cuLs.

Lxample: 12 y/o kld, wlLh u8l one week ago, presenLs wlLh eplsLaxls. erform L, and you see
leslons LhaL do nC1 blanch (need Lo know Lhe dlfference beLween peLechla and splder
anglomas: peLechlas do noL blanch b/c bleedlng lnLo Lhe skln, splder angloma WlLL blanch b/c
Av W ldlopaLhlc LhrombocyLopenlc
purpura. Mechanlsm: lgC agalnsL Lhe plaLeleL. WhaL Lype of P? ls Lhls? 1ype ll. Who ls
removlng Lhe plaLeleL? Macrophages ln Lhe spleen (b/c lgC marked Lhe plaLeleL for desLrucLlon
by Lhe macrophage). 1hls ls slmllar Lo auLolmmune hemolyLlc anemla, buL Lhls ls auLolmmune
1P8CM8CcyLopenla. 8x lf Lhey are very sympLomaLlc, glve corLlcosLerolds, lf noL, leave
alone and lL wlll go away.

Lxample: A , eplsLaxls, peLechla, generallzed Lender
lymphadenopaLhy, and splenomegaly. L has LuuS, auLolmmune LhrombocyLopenla, same
mechanlsm: lgC auLo-anLlbodles agalnsL plaLeleLs, a Lype ll P? rxn, wlLh macrophage relaLed
removal.

A. 11 (LhromboLlc LhrombocyLopenlc purpura) and nUS (hemolyLlc uremlc syndrome)
8oLh have slmllar paLhophyslology. 1hese are nC1 ulC, Lherefore you are noL
consumlng coagulaLlon facLors, Lhe 1 and 11 are LoLally and unequally normal. WhaL
you see ls a formaLlon of a Lemporary hemosLaLlc plug of small blood vessels (bleedlng
Llme) and Lhe coagulaLlon sysLem converLlng flbrlnogen Lo flbrln Lo form a sLrong
plaLeleL plug. So ln 11 and PuS, someLhlng ln Lhe plasma damages small vessels
LhroughouL your body, so LhaL plaLeleLs sLlck and plaLeleLs aggregaLe and evenLually
form flrm plaLeleL plugs ln all Lhe vessels of Lhe enLlre body. Would you consume all Lhe
plaLeleLs wlLh all LhaL sLlcklng golng on? ?es. Wlll you bleed b/c of LhaL? ?es. WhaL wlll
you see ln your perlpheral blood? 88C wlll be smashed, leadlng Lo schlsLocyLes.
1herefore you wlll have a mlcroanglopaLhlc hemolyLlc anemla. Ls wlll have
LhrombocyLopenla, fever, renal fallure (b/c glomerular caplllarles wlll have Lhese
plaLeleL plugs ln Lhem). AbsoluLely have Lo have schlsLocyLes ln Lhe perlpheral blood
wlLh hemolyLlc anemla Lo make Lhe dx.

1. 2 causes of PuS:

a) 0137:P7 L. coll (Loxln produclng L. coll LhaL can be presenL ln undercooked
beef. 1he Loxln damages Lhe vessel, leadlng Lo Lhe dz, and Lhls ls called PuS. Cne
of Lhe MC causes of acuLe renal fallure ln chlldren = PuS.
131


b) Shlgella Loxln (very poLenL) LhaL leads Lo shlgellosls and Lhen PuS.
ln 11/PuS wlll see low plaLeleL counL, prolonged bleedlng Llme, and normal
111
plaLeleLs.

V. Coagu|at|on def|c|ency

l C
W
pL has an operaLlon and Lhey sLarL bleedlng ouL of Lhe wound, Lhe MCC ls noL a coagulaLlon
facLor deflclency, Lhe MCC ls due Lo suLure sllpped or a bleed. When you have a coag
deflclency, [usL have Lo Lle lL off.

Lxample: molar exLracLlon wlLh consLanL oozlng of blood b/c noLhlng holdlng Lhose small
vessels LogeLher excepL a Lemp hemosLaLlc plug need a LlghL flbrln bond Lo plug lL up.

Lxample: lL ls showlng hemorrhage lnLo Lhe fasclal comparLmenL of Lhe Lhlgh. ln Lhe knee,
Lhere are repeaLed hemarLhroses and Lhe pL has hemophllla A. Wlll noL see hemarLhroses or
bleedlng lnLo spaces wlLh plaLeleL abnormallLles, buL only coagulaLlon facLor deflclency.

A. Must know the d|fference between hemoph|||a A and vW8 Dz (Lhese are Lhe key
coagulaLlon deflclencles)

1. vW8 Dz mlsslng vWl, Lherefore Lhere ls a plaLeleL adheslon defecL, Lherefore, Lhey
have all Lhe slgns and sympLoms of a LA1LLL1 problem. Powever, Lhey also have a
facLor 8 deflclency, buL lL ls very mlld and never severe. So, Lhey have 1WC
abnormallLles Lhey have a plaLeleL defecL Anu a coagulaLlon facLor defecL. 1hls ls why
Lhey can have menorrhagla and Cl bleedlngs (Lhls Lhe coagulaLlon parL of lL), wlll also
see hlsLory of eplsLaxls and Lhey brulse easy. 1here are 3 parLs of Lhe facLor 8 molecule:
vWl, facLor 8 coagulaLe (parL of lnLrlnslc sysLem), 8 Ag. 1he 8 Ag has a carrler funcLlon:
Wl - so lL
funcLlons as a carrler proLeln. All 3 of Lhese can be measured.

7uoo&u&?4
a) CeneLlcs: ln pLs wlLh hemo A x , Lherefore males geL
Lhe dz. Whereas vWuz ls AuLosomal domlnanL, and only one of Lhe parenLs have Lo
have Lhe abnormallLy and 30 of Lhe klds wlll have Lhe poLenLlal Lo geL Lhe dz.

132

b) number of deflclenL facLors: Pemophllla A only has one facLor LhaL ls deflclenL: 8
anLlcoagulanL, Lhey have normal 8 Ag levels and normal vWl levels. vWuz has ALL 3
Lhlngs decreased: 8 Ag, facLor 8 anLlcoagulanL (mlldly decreased), and vWl.

8. What drug can |ncrease the synthes|s of a|| three of these factor 8 mo|ecu|es? 1he drug
comes from AuP and ls called desmopressln (ddadp). 1hls can lncrease Lhe synLhesls of all
Lhree facLor 8 molecules. lL wlll help LreaL mlld hemophllla A, and ls Lhe uCC for vWuz.
ln woman, lf Lhey have menorrhagla and normal everyLhlng else, you have vWuz. 1hey puL
you on blrLh conLrol and LhaL Look Lhe bleedlng away. ln one of Lhe cases, Lhe ur. ordered
1, 11, and bleedlng Llme LesLs. 1he LesLs for 1 and 11 were normal and Lhe bleed Llme
was normal. 1he senslLlvlLy for Lhese LesLs ls only 30, so do noL depend on Lhese. 1he
rlsLocedln cofacLor assay ls Lhe LesL of cholce for vWuz, and wlll be abnormal. LsLrogen
lncreases Lhe synLhesls of all facLor 8 molecules.

So, 2 Lhlngs lncrease Lhe synLhesls of all Lhe facLor 8 molecules: desmopressln and blrLh
conLrol pllls (uCC for women).

C. USMLL Step 2: AnLl-phosphollplds syndrome (one of Lhe causes of sponLaneous
aborLlon) lncludes: Lupus anLlcoagulanL (noL an anLlcoagulanL, buL Lhe opposlLe:
Lhrombogenlc) and anLl-cardlollpln anLlbodles. 8oLh of Lhese anLlbodles cause vessel
Lhrombosls. Lupus anLlcoagulanL ls parL of Lhe syndrome LhaL produces vessel Lhrombosls.
Also seen ln Plv pL. AnLl-cardlollpln anLlbodles have a hlsLory of havlng a blologlcal false +
syphllls serology. So, here you are wlLh vu8L and 88 belng poslLlve. 1o conflrm, l1 A8S
would be negaLlve (LesL Ag ls beef cardlollpln). 1herefore makes Lhe vu8L and 88 false
poslLlve, b/c Lhe conflrmaLory LesL was negaLlve. So why was Lhe 88 poslLlve ln Lhe flrsL
place, b/c Lhe LesL anLlgen ls beef cardlollpln. 1herefore syphllls anLlbodles reacL Lo agalnsL
LhaL beef cardlollpln, and produclng a poslLlve reacLlon. 8uL so Lhe anLl-cardlollpln
1 l

geL? Serum anLl AnA anLlbody b/c she can develop lupus. AnLl-cardlollpln anLlbodles are a
very common feaLure of LuuS. M
ls a crlLerla for dlagnoslng Lupus.

133

D. D|ssem|nated Intravascu|ar Coagu|at|on (DIC)
ulssemlnaLed = all over Lhe body
lnLravascular = wlLhln Lhe vessel
CoagulaLlon = cloLLlng (formlng cloLs LhroughouL Lhe body)

WhaL ls consumed ln a cloL? llbrlnogen, 3, 8, proLhrombln, plaLeleLs

ln cloL Lube form a cloL on Lop ls serum and Lhe serum ls mlsslng whaL ls consume ln a cloL
(flbrlnogen, 3, 8, proLhrombln, plaLeleLs). 1hls ls whaL you have ln ulC consumlng Lhese
coagulaLlon facLors, lncludlng plaLeleLs, ln Lhose cloLs LhroughouL Lhe body, Lherefore you
?ou have (a) Lhrombl ln vessels, and aL Lhe same Llme you are (b)
anLlcoagulaLed b/c all you have clrculaLlng around l
consumed Lhe coagulaLlon facLorscalled a hemorrhaglc Lhrombosls syndrome. 1he
syndrome ls very unusual and Lwo Lhlngs are happenlng aL Lhe same Llme. WhaL sLarLed all
Lhls off? 1he lnLravascular coagulaLlon ls responslble for consumlng all Lhese Lhlngs.

So, whaL causes Lhls? MCC = SepLlc shock (MCC sepLlc shock = L. coll), snake blLe (noL Lhe
neuroLoxln Lypes, buL Lhe raLLlesnakes), and A8uS.
very slmple Lo recognlze Lhey bleed from every orlflce or scraLch, and even lf Lhere ls a
puncLure wound.

Classlc ulC = ux ls easy, b/c lf you consumlng all Lhe CoagulaLlon facLors, 1 and 11
. 1he LesL for ux ls u-dlmer LesL.

Lxample: pL wlLh abrupLlo placenLa and had amnloLlc fluld embollsm. AmnloLlc fluld geLs
lnLo clrculaLlon of Lhe mom, whlch conLalns LhromboplasLln, so, deaLh ls from ulC, noL from
Lhe amnloLlc embollsm. 8/c Lhe LhromboplasLln wlLhln Lhe amnloLlc fluld preclplLaLed ulC.

Lxample: heredlLary Lhrombosls = young person w/ uv1, noL normal and famlly hx

Lxample: facLor 3 lelden abnormal facLor 3 LhaL proLeln C and S cannoL breakdown,
Lherefore Lhere ls an lncrease ln facLor 3, whlch predlsposlng Lo Lhromboses

Lxample: AnLlLhrombln lll deflclency MCC woman blrLh conLrol (Lherefore, Lhe MCC ls
acqulred can also be geneLlc le pL wlLh uv1, puL on warfarln and heparln, and do a 11
ls normal afLer heparln, so you glve more heparln, and Lhe 11 ls sLlll normal. So, pL wlLh
uv1, glve heparln, 11 remalns normal = A1 lll def. b/c heparln works on A1 lll. normally,
Lhe heparln faclllLaLes anLlLhrombln lll Lhereby lncreaslng Lhe 11. ln Lhls case, no maLLer
how much heparln ls ln[ecLed, Lhere ls no change ln 11, Lherefore Lhere ls no AnLlLhrombln
lll for Lhe heparln Lo work on (Lhls ls how dx ls usually made by mlsLake).
134


L. Coagu|at|on d|sorders summary:
laLeleL cL/bleedlng Llme/1/11 (baslc LesLs Lo evaluaLe PemosLasls)
Asplrln: n, P, n, n
ldlopaLhlc LhrombocyLopenlc purpura (MCC of LhrombocyLopenla ln klds): L, P, n, n
11/PuS: L, P, n, n
Pemophllla A: n, n, n, P
vWuz: n, P, n, P (so, for lab LesLs, maln dlff from heme A ls bleedlng Llme)
warf/hep: n, n, P, P (ln8 1 = warfarln, , 11 = hep)

ulsease
laLeleL
CounL
8leedlng
1lme
1 11
Asplrln nL PlCP nL nL
l1 LCW PlCP nL nL
11/PuS LCW PlCP nL nL
Pemophllla A nL nL nL PlCP
vW8 uz nL PlCP nL PlCP
Warfarln/Peparl
n
nL nL PlCP (W) PlCP (P)
ulC LCW PlCP PlCP PlCP

VI. 8|ood Groups

A. D|fferent b|ood groups and what |s f|oat|ng around |n the serum: C ls mosL common, A
ls 2
nd
mosL common, 8 ls 3
rd
common, and A8 ls Lhe raresL
C: have anLl-A lgM, anLl-8 lgM, anLl-A8 lgC
A: anLl 8 lgM
8: anLl A lgM
A8: noLhlng
Newborn 1 lM are born and
only afLer 2-3 monLhs do Lhey sLarL synLheslzlng lgC.
L|der|y: noLhlng Lxample: an old person who ls blood group A and by mlsLake recelved
blood group 8, buL dld noL develop a hemolyLlc Lransfuslon rxn why? 1helr levels of
A
cells.

8. Assoc|ated D|seases:

Whlch ls assoclaLed wlLh gasLrlc cancer? A
Whlch ls assoclaLed wlLh duodenal ulcer? C
135

unlversal donor? C (can glve Lhelr blood Lo anyone b/c have nC anLl-A or anLl-8 Ag).
WhaL ls Lhe only blood group C can geL? C
u A8 A

C. Cther Ant|gens:
1. 8h u

2. uuffy Ag lkely Lo geL plasmodlum vlvax
A 88C u
A Cu SCu
from falclparum 88C so, Lhe
88C

D. Ma[or crossmatch: pL gonna geL blood, Lhelr serum ls ln a LesL Lube, wlLh Lhe blood of
Lhe donor unlL and Lhey mlx Lhe 2 LogeLher so Lhey m
88C
88C A
anLlbody screen whlch ls an lndlrecL
An1l8Cu?). lf Lhls LesL ls negaLlve, Lhe crossmaLch ls compaLlble (so, Lhere ls no Ab ln Lhe
1
A laLer agalnsL Lhe donor. WhaL ls Lhe chance LhaL anyone has Lhe same Ag
Z S l C l C
M u
necessary
Audlo uay 3: hemaLology 8
VII. S|de Notes
A. CuesLlons asked durlng Lhe break abouL hypersenslLlvlLy:
Lupus (noL everyLhlng ls Lype lll)
osL sLrep (noL everyLhlng ls Lype lll, elLher) can cause Lype ll lf lLs posL sLrep.
rheumaLlc fever, however, lf lL ls posL sLrep glomerulonephrlLls, LhaL ls Lype lll
1hrombocyLopenla and PemolyLlc anemla = Lype ll
Cn rash = Lype l
Cn ll lC A Cn 88C
membrane)

Lxample: mosL common Ab ln Lhe uSA ls AnLl-CMv (everyone has been exposed).

?ou are safesL from geLLlng Plv from blood Lransfuslon Lhan from all Lhe oLher lnfecLlons
(1/623,000 per unlL of blood chance of geLLlng Plv Lherefore uncommon geL Lo geL Plv
from blood). 1hls ls due Lo all Lhe screenlng LesLs LhaL Lhey perform. 1hey do Lhe Lllsa LesL
136

whlch looks for anLl- A -120 Ag LhaL aLLaches Lo helper 1
cell (Cu4) molecule C A
speclflc, so l
.
WhaL ls Lhe MC lnfecLlon LransmlLLed by blood Lransfuslon? CMv, whlch ls Lhe MC overall
lnfecLlon. 1haL ls why Lhls anLlbody ls Lhe mosL common.

WhaL ls MCC posL Lransfuslon hepaLlLls? Pep C (1/3000)

ln newborn, wanL Lo prevenL grafL vs. hosL dz and CMv b/c no lmmune defenses, Lherefore,
need Lo lrradlaLe Lhe blood. 1he lrradlaLlon kllls off Lhe lymphocyLes and slnce Lhe CMv
llves ln lymphocyLes, we klll off Lhe CMv vlrus also. 1hls why we radlaLe blood before glvlng
Lo newborns.

AccldenLal needle sLlck from a pL you know noLhlng abouL whaL ls Lhe MC lnfecLlon you
can geL? Pep 8.

A Plv Plv W
do you do abouL lL? ?ou go on Lherapy as lf you are Plv C 81l
AZ1 and a proLease lnhlblLor) for slx monLhs and geL consLanL checks do C8 LesL looklng
for 8nA ln Lhe vlrus (mosL senslLlve), do Lllsa LesL. ln facL, Lhe MC mechanlsm of a
healLhcare worker geLLlng Plv = accldenLal needle sLlck

uo noL Lransfuse anyLhlng lnLo a person unless Lhey are sympLomaLlc ln whaL Lhey are
deflclenL ln. Lxample: lf you have 10 grams of Pb, and have no sympLoms ln Lhe pL, do noL
Lransfuse. ?ou should Lransfuse Lhe pL lf Lhey have CCu and are sLarLlng Lo have anglna
relaLed Lo Lhe 10 grams. Lxample: 30,000 plaLeleL cL no eplsLaxls = do noL LreaL Lhem, lf
Lhey do have eplsLaxls, LreaL Lhe pL.

Lvery blood producL ls dangerous b/c you can geL lnfecLlons from lL.

8. Iresh frozen p|asma should never be used Lo expand a pLs plasma volume Lo ralse 8
use normal sallne (lL ls Loo expenslve and you run Lhe rlsk of LransmlLLlng dz). use fresh
frozen plasma for mulLlple coagulaLlon facLor deflclencles le would be leglLlmaLe Lo glve
frozen plasma Lo replace consumed facLors, as ln ulC.
Lxample: pL wlLh warfarln ls over anLlcoagulaLlon and bleedlng Lo deaLh noL Lo glve lM vlL
k wlll Lake Lo long Lo work (Lakes 6-8 hrs Lo work), so Lhe LreaLmenL of cholce ls fresh frozen
plasma Lo lmmedlaLely replace lL. So, fresh frozen plasma ls llmlLed Lo use of mulLlple
facLor deflclencles (le clrrhosls of Lhe llver and you are bleedlng slnce mosL of Lhe facLors
are made ln Lhe llver, Lhey are deflclenL ln all proLelns).
137

uCC for heparln overdose ls Lo glve proLamlne sulfaLe.

7g&0uoo&ou&&?

1. MC Lransfuslon rxn = a||erg|c rxn (lLchlng, hlves, anaphylaxls) - Lhls ls an example of a
Lype l P? rxn le have unlL of blood, and ln Lhelr plasma you are allerglc Lo someLhlng
(le Cn), 8x = benadryl, anLlhlsLamlnes

2. 2
nd
Lransfuslon rxn = febr||e rxn, PLA A PLA A L
leukocyLes of donor Ag. So, when Lhe unlL of blood ls Lransfused lnLo me, and Lhere are
some leukocyLes wlLh PLA Ab on Lhem, my Ab wlll reacL agalnsL lL, desLroy Lhe cell and
release Lhe pyogenes from neuLrophll, leadlng Lo fever.

l l l PLA A n ConLlnulng
quesLlon: Who ls mosL aL rlsk for havlng a febrlle rxn wlLh Lransfuslon? Woman b/c she
ls has been pregnanL every woman LhaL has had a baby has had a feLal maLernal bleed,
so some of Lhe bables leukocyLes goL lnLo Lhe bloodsLream, and Lhe woman developed
PLA A PLA Lhe husband, LhaL have been passed on Lo Lhe
S PLA A
develop b/c of her prevlous pregnancles. 1hls ls also Lrue for sponLaneous aborLlons
PLA A S re more llkely Lo have Lransfuslon lnduced
febrlle rxns b/c Lhey are more llkely Lo have anLl-PLA A
PLA

Lxample: Who has Lhe greaLesL rlsk ln developlng febrlle rxn? 1he answer cholces for
Lhls quesLlon would be a newborn, 12 y/o wlLhouL Lransfuslon, woman wlLh one
pregnancy, woman wlLh sponLaneous aborLlon, and man. 1he answer ls woman wlLh
sponLaneous aborLlon b/c LhaL ls a pregnancy and Lhere l PLA
leak ouL of Lhe feLus lnLo Lhe moLher.
lebrlle rxn ls a Lype ll P? rxn agalnsL Lhe PLA Ab (allerglc rxn ls Lype l)

3. nemo|yt|c transfus|on rxns are very rare. Lxample: lf you are blood group A, and
glven group 8 by sLupldlLy b/c Lhe pL has anLl-8 lgM (remember LhaL lgM ls Lhe mosL
poLenL complemenL acLlvaLor and LhaL cell wlll noL lasL only abouL 1 msec) 1hls ls b/c Lhe
lgM wlll aLLack lL, C1-C9: MAC, anaphylaLoxlns are released, and shock wlll ensue very
serlous aka clerlcal error).

Lxample A A 88C
happen b/c Lhe crossmaLch sald lL ls compaLlble, and dld an Ab screen LhaL was negaLlve
l C P A d you have memory 8 cells.
138

Suppose lf l goL blood Lransfuslon 30 years ago, Lhere are no Ab LlLers now b/c Lhey
8
Lhe senslLlvlLy of an Ab screen, come ouL compaLlble from a crossmaLch, and wlll have
neg lndlrecL coomb, however, afLer Lransfuslon, memory 8 cells would deLecL Lhe
forelgn Ag. AfLer Lhe 8 cell deLecLs Lhe Ag, lL wlll sLarL dlvldlng ln Lhe germlnal folllcle
and sLarL dlvldlng and become a plasma cell, whlch would make anLl-calla Ab. 1hls can
occur ln a few hrs or may occur ln a week A 1
llke on Lhe boards de|ayed hemo|yt|c transfus|on rxn.

Lxample: woman posLparLum, dlfflculL dellvery (abrupLlo placenLa) was Lransfused 3
unlLs of blood. When she lefL Lhe hosplLal, she had an Pb of Len. Cne week laLer, she ls
[aundlce and week, and has an uncon[ugaLed hyperblllrublnemla and has an Pb of 8.
WhaL ls Lhe dx? Pb was less Lhan whaL she lefL Lhe hosplLal, and Lhey wlll noL menLlon
Lhe coombs LesL) WhaL ls mosL llkely cause? PaloLhane (no b/c LhaL Lakes over a week
Lo develop), hepaLlLls (no, whlch Lakes 6-8 weeks Lo develop). Answer: delayed
hemolyLlc Lransfuslon rxn so, Lhey mlghL ask whaL LesL would you geL? lndlrecL coombs
LesL Lo prove lL b/c you wlll see Lhe Ab CoaLlng Lhe 88C. Moral of Lhe sLory? 1ransfused
w|th certa|n |eve| of nb, 1 week |ater have [aund|ce and |ess nb = de|ayed hemo|yt|c
transfus|on rxn = type II n

VIII. A8C]kh |ncompat|b|||ty

A. A8C |ncompat|b|||ty:
lf blood group C woman have a baby, Lhe mom wlll have a problem wlLh A8C
lncompaLlblllLy b/c mom already have an Ab LhaL can cross Lhe placenLa (blood group C
people have anLl A lgM, anLl 8 lgM and anLl A8 lgC, normally). normally, Lhere ls an anLl
A8 lgC Ab whlch can cross Lhe placenLa, and aLLack an A or 8 88C. So, Lhere could be a
problem ln Lhe very flrsL pregnancy.

Lxample: mom ls blood group C negaLlve and baby ls blood group A negaLlve. ls Lhere
an lncompaLlblllLy of blood groups? ?es. ls Lhere an lncompaLlblllLy ln 8h groups? no.
!usL Lhe blood groups, slnce Lhe mom ls C whlle baby ls A. 1he mom ls C, she has anLl
A8 lgC, whlch wlll cross Lhe placenLa, Lhe A parL of Lhe Ab wlll aLLach Lo Lhe A parL of Lhe
A 1
1 ll P?

wlll Lake care of lL. When Lhe baby ls born Lhe baby, lL wlll have a mlld anemla and
[aundlce. MCC [aundlce ln Lhe flrsL 24 hrs for a newborn = A8C lncompaLlblllLy (noL
physlologlc [aundlce of Lhe newborn LhaL sLarLs on day 3). Why dld Lhe baby develop
[aundlce? 8/c Lhe b
139

uncon[ugaLed blllrubln on lLs own now, so lL bullds up. 1hls ls an exchange Lransfuslon
rxn for A8C lncompaLlblllLy mosL of Lhe Llme ls b9, and puL under uv 8 llghL. Pow
does uv 8 llghL work? lL converLs Lhe blllrubln ln Lhe skln lnLo dl-pyrol, whlch ls waLer
soluble and Lhey pee lL ouL (8x for [aundlce ln newborn). Anemla ls mlld b/c lL ls noL a
A l
be poslLl lC 88C S C A A8
baby. 1hls can occur from Lhe flrsL pregnancy (noL llke 8h senslLlzaLlon where Lhe flrsL
pregnancy ls noL a problem). ln any pregnancy, lf mom ls blood group C, and she has a
baby wlLh blood group A or 8, Lhere wlll be a problem (blood group C = no problem).

8. kh |ncompat|b|||ty
Mom ls 8h negaLlve and baby ls 8h poslLlve. Lxample: mom ls C negaLlve and baby ls C
poslLlve (noL A8C lncompaLlble, buL 8h lncompaLlble). ln Lhe flrsL pregnancy: dellver
baby wlLhouL golng Lo a ur, and Lhere ls a feLal maLernal bleed, some of Lhe bables C
A S
8 Ab agalnsL lL. So, mom ls senslLlzed whlch means LhaL Lhere ls an Ab agalnsL LhaL u Ag
and now mom ls anLl u. 1 year laLer, mom ls pregnanL agaln, and sLlll C negaLlve, and
have anLl u and Lhe baby agaln ls C poslLlve. 1hls ls a problem b/c lL ls an lgC Ab, whlch
wlll cross Lhe placenLa, aLLach Lo Lhe bables u Ag poslLlve cells (of all Lhe Ags, Lhe u Ag
hosLs Lhe worsL hemolyLlc anemla). So, Lhe baby wlll be severely anemlc wlLh 8h Lhan
wlll A8C lncompaLlblllLy. 1he same Lhlng happens Lhough
Wen Lhe baby ls born, Lhe blllrubln
levels are very hlgh, a severe anemla occurs, and Lhere ls an excellenL chance LhaL an
exchange Lransfuslon wlll be necessary (99 chance), so Lake all Lhe blood ouL (geLs rld
88C Lransfuse b/c baby ls anemlc). So, Lhey wlll
usually always have a exchange Lransfuslon.

1herefore, for Lhe flrsL pregnancy, Lhe baby ls noL affecLed, and Lhls ls when Lhe moLher
geLs senslLlzed. ln fuLure pregnancles, Lhe baby wlll a loL worse.

Pow do we prevenL? Mom wlll do an Ab screen LesL and she ls 8h negaLlve. Around Lhe
28
Lh
week, glve her 8h lg, whlch ls prophylacLlc. 1hls ls anLl u, whlch comes from
woman, lL has been senslLlzed and heaL LreaLed and cannoL cross Lhe placenLa. Why do
Lhey glve aL 28 weeks? L may geL feLal maLernal bleeds before Lhe pregnancy or a car
S
u A u
1hen, mom glves blrLh Lo baby (leLs say lL ls 8h pos). uo a lyhowabenLl LesL and Lakes
lu 88C
how much ls ln Lhere. uependlng on LhaL, LhaL wlll deLermlne how many vlles of
140

allergen lg you glve Lhe mom Lo proLecL her furLher (anLl u only lasL Lhree monLhs, and
need Lo glve more aL blrLh, especlally lf Lhe baby ls 8h poslLlve).

Lxample: Mom: C negaLlve, 8aby: A poslLlve 2 problems: A8C lncompaLlble and 8h
lncompaLlble. 8uL, Lhere ls noL golng Lo be a prob wlLh senslLlzaLlon. no Why? AfLer
A
(whlch mom has anLl A lgM) , Lhose cells wlll be desLroyed so fasL, LhaL ln mosL cases Lhe
mom cannoL generaLe Ab agalnsL Lhose cells b/c Lhey have been desLroyed. So, A8C
lncompaLlblllLy proLecLs agalnsL 8h senslLlzaLlon. ?ou sLlll would glve 8h
lmmunoglobulln. So lf you are A8C and 8h lncompaLlble, 8h senslLlzaLlon wlll be
proLecLed agalnsL.

kld wlLh eryLhroblasLosls feLalls wlll have 8h lncompaLlblllLy whaL do Lhey dle of? PearL
fallure severe anemlas wlll decrease vlscoslLy of blood, so Lhey geL a hlgh ouLpuL
fallure: LPl, Lhen 8Pl, huge llvers b/c exLramedullary hemaLopoesls b/c Lhey are so
severe anemlc.

Lxample: cross secLlon of bralnsLem from kld whaL ls Lhe cause of color change? lLs
yellowlsh due Lo kernlcLerus prob from a baby LhaL had 8h lncompaLlblllLy.
8 uncon[ugaLed hyperblllrublnemla mla and
llpld soluble, llver cannoL syn lL, goes Lo braln and ls very Loxlc leadlng Lo severe
deblllLaLlng dz or deaLh.
141

Cardlology audlos- 4 hours LoLal

III. kxn to In[ury 1heory

Cells lnvolved- plaLeleLs, monocyLes, macrophages, cyLoLoxlc L cells wlLh cyLoklnes
(neuLrophlls noL lnvolved)

ALherosclerosls ln an aorLa rxn Lo ln[ury Lheory = ln[ury Lo endoLhellal cells llnlng Lhe elasLlc
arLerles and muscular arLerles whaL ls ln[urlng lL? Ammonla ln clg smoke, CC ln clg smoke, so,
polsons damage Lhe endoLhellal cells, LuL damages lL, and lf lLs oxldlzed, lL damages lL worse,
vlral lnfecLlons damage lL, Loo. Ch|amyd|a pneumon|ae (2
nd
MCC atyp|ca| pneumon|ae), pts
w|th MI q S v- q>- -k homocyste|ne a|| these th|ngs
damage endothe||a| ce||s

WhaL happens when you damage endoLhellal cells? laLeleLs sLlck Lo lL and uCl ls released
lnLo Lhe arLery and uCl causes smooLh muscle cells wlLhln Lhe medla Lo prollferaLe and Lhey
undergo hyperplasla and Lhen, Lhey chemoLacLlcally mlgraLe Lo Lhe sublnLlmal level. 1hey
have all Lhese smooLh muscle cells mlgraLlng Lo Lhe lnLlma of Lhe vessel. MonocyLes have
access lnLo Lhe vessel b/c lL has been ln[ured and monocyLes also have Cls. As Lhe LuL
lncreases, Lhe macrophages phagocyLose Lhem. Macrophages and smooLh cells have LuL w/ln
Lhem, Lhe LuL becomes oxldlzed and a faLLy sLreak ls produced. Cver Llme, a flbrofaLLy plaque
develops, whlch ls paLhognomonlc of aLherosclerosls. lL can be compllcaLed by dysLrophlc
calclflcaLlon, flssurlng, Lhrombosls and a compllcaLed aLherosclerosls.

IV. Arter|a| D|sorders:
70>uuu\oou&? ]
CAu, aLheroscleroLlc sLroke relaLes Lo plaques, abdomlnal aneurysm due Lo weakenlng of Lhe
vessel, nonLraumaLlc ampuLaLlon of lower exLremlLy (perlpheral vascular dz), mesenLerlc
anglna, small bowel lnfarcLlon, renovascular aLherosclerosls of Lhe renal arLerles.
Atherosc|eros|s on|y |nvo|ves muscu|ar arter|es and e|ast|c arter|es. Can small vessel, such as
arLerloles geL hardened? ?es. Lxample: look aL Lhe spleen hyallne arLerlolar sclerosls and
hyperplasLlc arLerlolar sclerosls (onlon sklnnlng).



1. nya||ne arter|osc|eros|s ls a small vessel dz, lumen ls narrow, whenever Lhere ls a loL of
plnk sLalnlng sLuff, Lhls ls hyallne. Lxample: small vessel dz of dlabeLes and P1n Lwo ma[or


142

a. D|abetes: nonenzymaLlc glycoslyzaLlon aka PbA1c, glycoslyzaLlon ls glucose aLLachlng Lo
aa and proLeln. lor PbA, lLs glucose aLLachlng Lo aa and PbA, and Lhe PbA ls glycosylaLed.
PbA1c levels correlaLe wlLh Lhe blood glucose levels of Lhe lasL 6-8 weeks, so Lhls ls Lhe besL
way of looklng aL long Lerm glucose levels. All Lhe damage seen ln dlabeLes ls due Lo glucose.
lor a dlabeLlc, you should be under 6, meanlng LhaL you are ln a normal glucose range. 1here
ls noLhlng unlque abouL dlabeLes excepL for a large glucose level, you keep LhaL normal, and
1 on|y two patho|og|c processes are th|s: nonenzymat|c
g|ycosy|at|on 8v osmot|c damage. 1hose
Llssues LhaL conLaln aldose reducLase lens, perlcyLes ln Lhe reLlna, schwann cells all have
aldose reducLase and can converL glucose lnLo sorblLol and sorblLol ls osmoLlcally acLlve sucks
waLer lnLo lL and Lhose cells dle, leadlng Lo caLaracLs, mlcroaneurysms ln Lhe eye b/c Lhe
perlcyLes are desLroyed and weakened and Lhe reLlnal vessels geL aneurysms, and you geL
perlpheral neuropaLhy b/c schwann cells are desLroyed. 1hey all relaLed Lo excess glucose. So,
LlghL glucose conLrol = normal llfe.


WhaL does nonenzymaLlc glycosylaLlon Lo do Lhe basemenL membrane of small vessels? lLs
renders Lhem permeable Lo proLeln, so Lhe proLeln ln Lhe plasma leaks Lhrough Lhe 8M and
goes lnLo Lhe vessel wall, produces a hyallne change and narrows Lhe lumen. WhaL lf Lhere ls
nonenzymaLlc glycosylaLlon of Lhe C8M? lL wlll render lL permeable Lo proLeln called
mlcroalbumlnurla. 1hls ls Lhe flrsL change Lo be seen ln dlabeLlc nephropaLhy. So, whaL ls Lhe
mechanlsm? nonenzymaLlc glycosylaLlon.

b. nypertens|on
uoes noL use nonenzymaLlc glycosylaLlon. lL [usL uses brulL force and drlves (b/c of lncrease ln
dlasLollc pressure) Lhe proLelns Lhrough Lhe 8M and produces Lhe effecL. When we look aL a
kldney ln P1n, lL ls shrunken, has a cobblesLone appearance Lhls ls b/c Lhere ls hyallne
arLerlolosclerosls of Lhe arLerloles ln Lhe corLex, lschemla, and ls wasLlng away wlLh flbrosls
and aLrophy of Llssue. Lacunaer sLrokes (Llny areas of lnfarcLlon LhaL occur ln Lhe lnLernal
capsule) are a hyallne arLerlosclerosls problem relaLed Lo P1n.

2. nyperp|ast|c arter|osc|eros|s
Seen ln mallgnanL P1n, more common ln blacks Lhen whlLes, malnly b/c P1n ls more common
ln blacks Lhan whlLes. Malnly see Lhls vessel dz ln mallgnanL P1n (le when pL has 8 of
240/160).

8. Aneurysm
1. Def|n|t|on: area of ouLpouchlng of a vessel due Lo weakenlng of Lhe vessel wall.
ALherosclerosls can cause weakenlng of Lhe abdomlnal aorLa leadlng Lo an aneurysm.

143

WhaL would be Lhe analogous leslon ln Lhe lungs wlLh weakenlng and ouLpouchlng?
8ronchlecLasls due Lo cysLlc flbrosls wlLh lnfecLlon, desLrucLlon of elasLlc Llssue leadlng Lo
ouLpouchlng and dllaLaLlon of Lhe bronchl. Lxample: whaL ls Lhe Cl aneurysm? ulverLlcular dz
have a weakenlng and ouLpouchlng of mucosa and submucosa

2. Law of Lap|ace Lhe wall sLress lncreases as radlus lncreases. ln Lerms of Lhls, once you
llaLe someLhlng, you lncrease Lhe wall sLress and
evenLually lL rupLures. So, ln oLher words, all aneurysms wlll rupLure
when.

3. Abdom|na| Aorta Aneurysm: Why ls Lhe abdomlnal aorLa Lhe MC area of aneurysm? 8/c
Lhere ls no vasa vasorum or blood supply Lo Lhe aorLa below Lhe renal arLerles. So, Lhe only
C So, parL furLhesL
from lL mgeLs screwed. 1herefore, aparL from Lhe parL LhaL ls noL geLLlng much C2 and
nuLrlenLs, lL wlll be more suscepLlble Lo ln[ury, Lherefore aLherosclerosls leads Lo weakenlng of
Lhe wall and aneurysm/ln[ury occurs.
a. MC compllcaLlon abdomlnal aorLlc aneurysm = rupLure. 1he tr|ad of s]s are: a sudden
onseL of severe lefL flank paln b/c Lhe aorLa ls reLroperlLoneal organ and so lL does noL bleed
lnLo Lhe perlLoneal cavlLy, buL lnLo Lhe perlLoneal Llssue. So, severe |eft f|ank pa|n, nypo1N,
and pu|sat||e mass on L. 1hese are Lhree Lhlngs LhaL always occur when Lhere ls a rupLured
aorLlc abdomlnal aneurysm. MC comp||cat|on of any aneurysm = rupture

4. Aneurysm of the arch of the aorta ] MCC = tert|ary syph|||s. aLhology of syphllls ls
vascullLls of arLerloles. Chancre, Loo. lLs palnless b/c lf you secLlon lL, you wlll see llLLle
arLerloles surrounded by plasma cells and Lhe lumen of Lhe vessel ls compleLely shuL, so lL ls
lschemlc necrosls. ln oLher words, lL ls lschemla of Lhe overlylng Llssue undergolng necrosls.
8/c nerves are nexL Lo vessels, Lhey are knocked off, Loo, and lL ls palnless. A|| of syph|||s |s a
vascu||t|s. 1haL ls whaL Lhe !"#$%&#'( lnfecLs small vessels and arLerloles. WhaL are Lhey
affecLlng ln Lhe arch of Lhe aorLa? 1he vasa vasorum, Lhe rlchesL supply of vasa vasorum ls ln
Lhe arch, so lLs loglcal LhaL Lhe !"#$%&#'( wlll plck lL leads Lo endarLerlLls obllLerans (Lhey
are obllLeraLlng Lhe lumen), lschemla, weakenlng under sysLollc pressures, leads Lo depresslon
W Llc valve rlng?
lL wlll sLreLch lL whlch murmur wlll Lhls lead Lo? AorLlc regurg. Murmurs can occur b/c Lhere
ls valvular damage or b/c Lhe valvular rlng ls sLreLched. So, Lhere can be sLreLchlng of Lhe rlng
and noLhlng wrong wlLh Lhe valves, and have a murmur, or you can have damage Lo Lhe valves
and have a murmur. Syphllls ls an example of sLreLchlng of Lhe aorLlc valve rlng leadlng Lo a
murmur and aorLlc regurg.

AorLa should be closlng durlng dlasLole as you pump Lhe blood ouL, and Lhe Sv goes down,
and b/c Lhe aorLlc cannoL close properly, only some of Lhe blood wlll drlp back ln. So you wlll
144

have more volume of blood ln Lhe lefL venLrlcle ln someone wlLh aorLlc regurg. lrank-sLarllng
forces wlll be worklng. As you sLreLch cardlac muscle, you lncrease Lhe force of conLracLlon.
n Ll L
have 200 mls of blood ln Lhe Lv b/c blood ls drlpplng back ln, and frank-sLarllng force geLs ouL
100 mls of blood, whlch has Ll S 1 -sLarllng
occurs ln a paLhologlc condlLlon. l
noL good b/c Lhelr head ls wobbllng, and when Lhey open Lhelr mouLh you can see uvula
pulsaLlng, can Lake Lhelr nall and llfL lL up and see pulsaLlons of Lhe vessels under Lhe nall,
WaLer-hammer pulse, and when llsLenlng wlLh Lhe sLeLhoscope of Lhe femoral arLery you can
u 1 Sv elaLed Lo Lhe facL LhaL
Lhere ls more blood ln Lhe Lv. syphlllLlc aneurysms of Lhe abdomlnal aorLa ls Lhe classlc
example of Lhls. AnaLomy correlaLlon: Lhe LefL 8ecurrenL Laryngeal nerve wraps around Lhe
arch and Lherefore can geL hoarseness. Agaln Lhe MC compllcaLlon ls rupLure.

S. D|ssect|ng aort|c aneurysm:
a. key factor that causes a tear |n the aorta |s n1N b/c lL lmposes sLress on Lhe wall of Lhe
vessel. 1here musL be weakenlng Lhe elasLlc arLery and ls caused by elasLlc Llssue
fragmenLaLlon. Cyst|c med|a| necros|s CAC
muclnous maLerlal w/ln, and walls of aorLa rub upon lLself, and when addlng a llLLle blL of P1n
leads Lo a Lear. Wherever Lhe area of weakness ln Lhe elasLlc arLery ls where Lhe blood wlll
dlssecL and Lear blood can go Lo Lhe perlcardlal sac, leadlng Lo cardlac Lamponade. 1hls ls
called Lhe proxlmal dlssecLlon (MC). MosL of Lhe Lears up ln Lhe arch, Lherefore you would
Lhlnk Lhe pL may have an absenL pulse, Lhls ls very common ln pLs wlLh Lears LhaL are proxlmal.
When lL dlssecLs, lL closes lumen Lo subclavlan arLery and lL usually dlssecLs on Lhe lefL and
causes an absenL pulse on lefL.

b. Chest pa|n ln Ml ls dlff Lhan Lhe chesL paln ln a dlssecLlng aneurysm. Ml has chesL LlghLness
radlaLlng Lo lefL arm and [aw, ln aorLlc dlssecLlon, Lhere ls a Learlng paln radlaLes Lo Lhe back,
and ls a reLrosLernal paln. ulse on lefL ls dlmlnlshed vs. Lhe one on Lhe rlghL. Cn chesL x-ray,
wldenlng of Lhe aorLlc knob. WlLh blood Lhere, dlameLer of aorLa wlll be enlarged, as seen on
x-ray, and Lhls LesL ls 83 senslLlve ln deLecLlng lL, Lherefore lL ls Lhe screenlng LesL of cholce,
see wldenlng of Lhe prox|ma| aort|c knob. 1o prove, do Lransesophageal ulLrasound or
anglography Lo conflrm dx.

7)&?&uuuu& :
(1) Marfan syndrome (eunochold proporLlons hL of pelvlc brlm Lo feeL ls greaLer Lhan from
pelvlc brlm Lo Lhe head. Also, anoLher deflnlLlon ls LhaL arm span ls greaLer Lhan Lhe helghL. Au
lnherlLance, c , defecL ln flbrlllln, whlch ls a componenL ln elasLlc Llssue. uue Lo Lhe
defecL ln flbrlllln, Lhe elasLlc Llssue ls weak Lhls ls why Lhey have dlslocaLed lenses and have
dlssecLed aorLlc aneurysms (MCC deaLh ln marfans ls Mv).
145


(2) Lh|er Dan|os has a collagen defecL, MCC of deaLh

(3) regnant women are suscepLlble Lo dlssecLlng aorLlc aneurysms b/c ln pregnancy Lhey
have Lwlce Lhe amounL of plasma vol vs. a non-pregnanL woman. 1here ls an lncrease of
88C s a 2:1 raLlo of lncreaslng plasma vol Lo 88C mass,
P 1
hemoglobln, usually around 11.3 ls Lhelr cuLoff for anemla and Lhe cuLoff ls 12.3 for normal
women. 1hls ls b/c of dlluLlonal effecL wlLh excess ln plasma vol. ApparenLly ln some women,
Lhe excess plasma volume for 9 monLhs can cause weakenlng of Lhe aorLa and Lhereby causlng
an aneurysm.

V. Venous D|sorders:
A. Super|or vena cava |ung syndrome ln a smoker wlLh prlmary lung cancer, now complalnlng
of headache and blurry vlslon look aL hls reLlna and see reLlnal veln engorgemenL, and
congesLed dx? Super|or vena cava |ung syndrome usually due Lo prlmary lung cancer
knocklng off Lhe sup vena cava, leadlng Lo backup of venous blood lnLo Lhe [ugular venous
sysLem and Lo Lhe dural slnuses, Lhls ls a very bad dz, and wlll lead Lo deaLh. usually LreaL wlLh
u ancoast 1umor
P S SvC P
opposed Lo ancoasL.
8. Var|cose Ve|ns

VI. 1umors of 8|ood Vesse|s:

A. Sturge Weber syndrome

P Av
predlsposlng Lo bleedlng. So, noL only a vascular malformaLlon of Lhe face, buL also an Av
malformaLlon ln Lhe same slde of Lhe braln, whlch predlsposes Lo bleedlng. Also, Lhese pLs are
a llLLle menLally reLarded. (some pLs show lL on Lhe enLlre slde of Lhe face)

8. Cs|er Weber kendu aka nered|tary hemorrhag|c te|ang|ectas|a small LelanglecLasla ln Cl.
Au lnherlLance characLerlzed by locallzed LelanglecLases of Lhe skln and mucous membranes
and by recurrenL hemorrhage from Lhese leslons.

C. Sp|der ang|oma]sp|der te|ang|ectas|a: lf you press down on Lhls, Lhe llLLle LenLacles wlll go
away (Lherefore lL blanches) called splder angloma. lL ls due Lo hyperesLrlnlsm. 1hls ls
normal ln pregnancy. lf a male has splder angloma, he has clrrhosls (MCC clrrhosls = alcohol).
Why would a male have a splder angloma? 8/c lf you have clrrhosls, you cannoL meLabollze
146

esLrogen so lL bullds up, leadlng Lo gynecomasLla, warm skln, palmer eryLhema, and splder
angloma relaLed Lo hyperesLrlnlsm. AnoLher reason would be b/c Lhey cannoL meLabollze 17
keLosLerolds elLher, Lherefore Lhey wlll be aromaLlzed Lhose ln Lhe adlpose Llssue lnLo
esLrogen. So, Lhey are 2 ways of geLLlng hyperesLrlnlsm ln clrrhosls. So, how ls Lhls dlfferenL
l Av ln
oLher words, Lhe blood goes dlrecLly from arLerlole Lo a venule and ls bypasslng Lhe caplllarles.

D. Cap|||ary nemang|oma: plc of chlld wlLh red leslon (noL bllaLeral wlde eye leslon so lLs
noL reLlnoblasLoma), whaL do you do? Leave |t a|one, do noL surglcally remove b/c by 8 y/o, lL
wlll be gone so, leave caplllary anglomas alone b/c Lhey wlll go away.


L. 8ac|||ary ang|omatos|s:
kaposl sarcoma ls caused by Lhe PPv 8 organlsm. lf Lhere was a leslon seen only ln Alus pLs
k ls due Lo bacLerla bac|||ary
ang|omatos|s due to bartene||a hens||a| seen wlLh sllver sLaln. 8x? Sulfa drug. 1hls
organlsm also causes CaL ScraLch uz.

I. Ang|osarcoma of the ||ver vA1 vlnyl chlorlde (people who work wlLh
plasLlcs and rubber), Arsenlc (parL of pesLlcldes, conLamlnaLed waLer), and 1horoLrasL (a
radloacLlve dlagnosLlc agenL Lhorlum dloxlde).

VII. Vascu||t|s Syndromes

A. Concept of Vascu||t|s: vascullLls of small vessels (arLerloles, venules, caplllarles), muscular
arLerles, and elasLlc arLerles. All of Lhese vascullLls presenL wlLh dlfferenL slgns and sympLoms
(le llke coagulaLlon dlsorders vs. plaLeleL dlsorders).

1. Sma|| vesse| vascu||t|s 99 of Lhe Llme lL ls due Lo a Lype lll P?, meanlng lL ls lnvolves
lmmune complex deposlLlon, LhaL wlll deposlL ln Lhe small vessel, acLlvaLe complemenL and
aLLracL neuLrophlls (C3a), and wlll geL flbrlnold necrosls and damage Lo Lhe small vessel and
ALA8LL UkUkA, (remember Lhe old person wlLh purpura on Lhe back of Lhe hand LhaL
was noL palpable and was due Lo hemorrhage lnLo Lhe skln, Lhere was no lnflammaLory
problem lL [usL rupLured lnLo Lhe skln) buL lf lL was palpable, lL would be consldered a SMALL
vLSSLL vascullLls noL a plaLeleL problem.
Lxample:
LeukocyLoclasLlc vascullLls (hypersenslLlvlLy vascullLls),

Penoch-Schonleln purpura. So, SMALL VLSSLL vascu||t|s = ALA8LL purpura (a|ways to|d |n
the stem of the quest|on).
147


2. Muscu|ar artery vascu||t|s olyarLerlLls nodosa and Wegener granulomaLosls. 1hese wlll
geL 1P8CM8CSlS of Lhe vessel, noL palpable purpura. Wlll have INIAkC1ICN. Lxample:
k u
geL coronary arLery vascullLls MCC Ml k b/c parL of Lhe
syndrome, ln addlLlon Lo mucocuLaneous lnflammaLlon, desquamaLlon of skln, and
lymphadenopaLhy, Lhere ls a coronary arLery vascullLls Lhrombosls occurs and llLLle chlld wlll
have an lnfarcLlon. So, |nfarct|on |s what you see w|th a muscu|ar artery vascu||t|s.
Lxamples n W k

3. L|ast|c artery vascu||t|s When you knock off an elasLlc arLery, Lhen you deal wlLh arch
1 Lhe vascullLls wlll block off Lhe
lumen of one of Lhe arch vessels, leadlng Lo S1kCkLS and can knock off Lhe lnLernal caroLld.
Lxample 1 young, far easLern lady wlLh absenL pulse.

So, pa|pab|e purpura = sma|| vesse| vascu||t|s
Infarct|on = muscu|ar vascu||t|s
Invo|ves pu|se]stroke = e|ast|c artery vascu||t|s

8. 1empora| Arter|t|s unllaLeral headache, aches and palns all over body, loss of vlslon of
same slde of headache, hurLs when pL chews ln Lemporal area. 1hls ls a granulomaLous (have
mulLlnucleaLed glanL cell) vascullLls of Lhe Lemporal arLery, a Lype of glanL cell arLerlLldes. lL
can lnvolve oLher porLlons of Lhe arLery lncludlng Lhe ophLhalmlc branch and produce
bllndness. 1 CnL?
arLerlLls. Why? noL LhaL lL ls speclflc, buL b/c Lhls ls an arLerlLls, (an lnflammaLlon) Lhe sed raLe
should be elevaLed. lf Lhe sed raLe ls nC1 elevaLed, lL could be a LranslenL lschemlc aLLack.
1hls ls good screen b/c lL Lakes Llme Lo Lake a blopsy and look aL lL, and Lhe pL could go bllnd.
So, you musL puL Lhe pL on corLlcosLerolds lmmedlaLely (rlghL Lhere and Lhen) [usL based on hx
alone. 1he pL wlll be on corLlcosLerolds for one year. l
rheumaLlca muscle aches and palns 1
olymyalgla rheumaLlca does noL have an elevaLlon of serum Ck, and have aches and palns of
muscl l

C. 8uerger dz (aka thromboang||t|s ob||terans smokers dz

males, young, dlglLal vessel Lhrombosls, leadlng Lo auLolnfarcLlon of Lhelr flngers, Anu Loes.
l -slzed arLerles.

nenoch-Schon|e|n purpura: (buLL, [olnLs, glL, renal,skln) (palpable purpura on buLL, n legs, [olnL
probs, and kldney probs)
148

14 y/o, u8l one week ago, presenLs wlLh polyarLhrlLls, [olnL palns, hemaLurla, wlLh 88C casLs
and palpable purpura of buLLocks and lower exLremlLy dx? Penoch-Schonleln purpura = MC
vascullLls ln chlldren lmmune complex (as ls all small vessel vascullLls) anLl lgA lmmune
complex, and Lhe 88C casLs are due Lo glomerulonephrlLls. uo noL confuse wlLh lgA
glomerulonephrlLls 8

L. Wegener granu|omatos|s
-|f u had to go ||sten to wagner |n concert, you wou|d pretend u had to use the bathroom or
get pneumon|a
,-kSk |ung, urt, rena| , sadd|e nose ,canca >q-6
pL wlLh saddle nose deformlLy (noL congenlLal syphllls) also probs wlLh slnus lnfecLlons,
u8l dx? Wegener granulomaLosls
(MCC of saddle nose deformlLy). 1hls ls a granulomaLous lnflammaLlon Anu vascullLls.
1herefore, lL lnvolves Lhe upper alrways, lungs, and kldneys, also, Lhere ls an Ab LhaL ls hlghly
speclflc for lL
c-ANCA (ant|-neutroph|| cytop|asm|c Ab). kx - Cyc|ophospham|de (whlch can lead Lo
hemorrhaglc cysLlLls and bladder cancer and how can you prevenL Lhe hemorrhaglc cysLlLls?
Mesna).

I. o|yarter|t|s Nodosa

male domlnanL dz LhaL lnvolves muscular arLerles, Lherefore lnfarcLlon ls a parL of lL. Pas p-
f q-vq-- -qU kvS- . Lxample: have lvuA wlLh
chronlc Pep 8 who has a nodular lnflamed mass on Lhe lower exLremlLy and hemaLurla (due Lo
kldney lnfarcL), whaL does Lhe pL have? olyarLerlLls nodosa b/c Lhe pL has a chronlc hep 8
lnfecLlon Lherefore has hep 8 surface anLlgens. So, remember p-ANCA and nep 8 surface Ag.

G. 8acter|a| |nfect|ons: vessel ln kMSI. 1he rlckeLLslal organlsms lnfecL endoLhellal cells, Lhe
spoLs are peLechla, unl sLarLs on Lhe exLremlLles and
goes Lo Lhe Lrunk (whereas oLhers sLarL on Lhe Lrunk and Lo Lhe exLremlLles). Also have Lo
C L b. recurenLls
ls relapslng fever, and has anLlgenlc shlfLs, lL ls a splrocheLe (LepLosplra and syphllls are also
splrocheLes). So, 3 splrocheLes L 1 8 8L1

I. Iungus LhaL ls wlde angle, nonsepLaLe , pL has ukA, and cerebral abscesses relaLed Lo
fungus mucormycos|s (know relaLlonshlp of Lhls fungus and ukA),
ulabeLlcs commonly have mucor ln Lhelr fronLal slnuses, so when Lhey go lnLo keLoacldosls and
sLarL prollferaLlng, Lhey go Lhrough Lhe crlblform plaLe lnLo Lhe fronLal lobes where Lhey lnfarcL
lL and lnfecL lL wlLh Lhe dz.

149

VIII. Iunct|ona| Vascu|ar D|sorders: kaynaud Dz
1 A
8 anosls ln Lhe nose and
ears (LhaL comes and goes away), so, lL ls due Lo lgM cold aggluLlnln dz or cryogloblnemla ln
old man wlLh Pep C.

P co||agen vascu|ar dz and flrsL manlfesLaLlon ls
8 l vascullLls and evenLually a flbrosls progresslve sysLemlc
sclerosls (aka scleroderma), and lLs counLerparL C8LS1 syndrome.
vascullLls of flngers and leads Lo flbrosls wlll evenLually auLo- 8

CkLS1 syndrome Calclnosls (dysLrophlc calclflcaLlon) and CenLromere Ab (speclflc for cresL
syndrome), 8, Lsophageal dysmoLlllLy, SclerodacLyly (flnger LhaL ls very narrow),
1elanglecLasla (very slmllar Lo Lhe pln polnL hemorrhages also seen ln Csler Weber
8endu).***********

CLher causes due Lo vasoconsLrlcLlon common ln pLs LhaL Lake drugs for mlgralne drugs for
mlgralnes cause vasoconsLrlcLlon of vessels. So, 8 L
derlvaLlves, 8uerger dz, Loo.

x0o/ 8&> o0&? : vasoconstr|ct|on, vascu||t|s of the d|g|ts (|e CkLS1
>k>-vSv>>-I

Ik. nypertens|on (n1N)

MCC deaLh wlLh P1n = Ml (2
nd
= sLroke, 3
rd
= renal fallure)
LssenLlal P1n= MC

A. Mu|t|factor|a| Inher|tance: WhaL raclal group has hlghesL lncldence of P1n? 8lacks. Why?
MulLlfacLorlal lnherlLance CAu 1 ll
dlabeLes, affecLlve dlsorders, congenlLal pylorlc sLenosls, essenLlal P1n). 1hls means LhaL you
have a Le lC8 W 8 MuL1l

Lxample: l am black, whaL should l do Lo prevenL from geLLlng lL? l cannoL geL rld of geneLlcs,
and my geneLlcs are LhaL l cannot get r|d of sa|t |n my ur|ne - reLalnlng Loo much salL (wh|ch |s
the bas|c mechan|sm of essent|a| n1N |n b|acks and e|der|y). So, cannoL conLrol geneLlcs, buL l
can conLrol 3 Lhlngs: (1) welghL has a dlrecL correlaLlon wlLh P1n, (2) reduce salL lnLake, and
(3) exerclse. Lxample: famlly hx of gouL, whaL can l do so l avold gouL? Avold red meeL, no
alcohol (whlch wlll decrease purlne meLabollsm). Lxample: lf you had a famlly hx of uM Lype
150

ll be sklnny (lean and mean) as you lose adlpose, upregulaLe lnsulln recepLor synLhesls and
LhaL alone could prevenL you from havlng Lhe dz.

8. Mechan|sm of n1N b/c you reta|n sa|t MC
When you reLaln salL, whaL comparLmenL wlll Lhe salL be reLalned ln? LCl lf LhaL ls Lrue, whaL
wlll be Lhe plasma volume lf you have excess salL ln your vascular and lnLersLlLlal
comparLmenL? lncreased lf your plasma vol ls lncreased, your sLroke volume wlll be
lncreased whlch ls your systo||c n1N (b]c |ncrease |n LASMA vo|). When you have excess
salL, salL wanLs Lo go lnLo smooLh muscle cells (lnLo perlpheral reslsLance arLerloles). When
sodlum enLers muscle, lL opens cerLaln channels for Ca Lo go ln, Ca goes ln and smooLh muscle
wlll conLracL, so Lhe perlpheral reslsLance arLerloles are vasoconsLrlcLlng. 18 =
vlscoslLy/radlus
4
, we are decreaslng radlus, lncreaslng reslsLance, and reta|n|ng more b|ood |n
the arter|o|e system (that reg|sters as an |ncrease |n d|asto||c pressure). 1hls ls why Lhe 8x of
cholce for essenLlal P1n ln blacks and elderly = hydrochloroLhlazlde b/c you rld salL and
waLer Lo decrease 8, however, do noL use lf pL has hyperllpldemla, so use ACL lnhlblLors.

ls Lhls a hlgh or low renln Lype of P1n? Low renln b/c lncreased plasma volume = lncreased
blood flow Lo Lhe renal arLery = decreased renln S P1n

C. Comp||cat|ons: P1n ls a ma[or rlsk facLor for CAu, leadlng Lo MI (MCC death). SLroke = #2.
8lood ls locaLed ln globus pallldus and/or puLamen P1n
bleeds occur ln Lhe braln. 1hls ls b/c Lhe lenLlculosLrlaLe vessels (whlch are small vessels of Lhe
mlddle cerebral arLery) under lncreased pressure form aneurysms called Charcot 8ouchard
aneurysms, and Lhey rupLure. 1hls ls noL a good place Lo rupLure. 1herefore, Lhls ls noL an
lnfarcL lL ls a hemaLoma n
1herefore Lhe 2
nd
uq- U7fS > . Lxample: kldney LhaL ls Loo small wlLh a
pebbly surface due Lo hyallne arLerlolosclerosls a small vessel dz ls causlng lschemla of Lhe
kldney, aLrophy of Lubules, desLrucLlon of glomerull, shrlnkage of kldney, and leads Lo kldney
fallure. 1hls ls Lhe 3
rd
MCC death |n n1N. MC overall abnormallLy ln P1n = LvP (mech:
afLerload prob b/c Lhe hearL has Lo conLracL agalnsL lncreased reslsLance and lf lL remalns over
a perlod of Llme lL wlll evenLually lead Lo hearL fallure.




Audlo Cardlovascular 2
CnA1Lk 7: CAkDICVASCULAk
1nL nLAk1

I. nypertrophy of the neart:
151


-q-#UkSqI->Ukq eart: 2 dlfferenL eLlologles, and Lhey lnvolve
work. lL requlres a loL of work Lo conLracL and push blood Lhru a sLenoLlc aorLlc valve, or
lncreased 18 from P1n. 1hese wlll cause an |ncreased after|oad = concentr|c n.
lf you have a valvular problem, and have excess volume of blood ln Lhe venLrlcles lncreased
preload = lncreased work. 1herefore, Lhe frank sLarllng goes lnLo effecL b/c sLreLchlng and
lncreaslng preload ln Lhere, and you have Lo work harder Lo lncrease Lhe force of conLracLlon
Lhls produces dllaLed P?. 1herefore, concentr|c n = after|oad prob|em, d||ated n =
vo|ume over|oad = pre|oad prob|em (|ncreased vo|ume)

II. neart sounds ]

S1 heart sound = beglnnlng of SysLole = mlLral and Lrlcusplds close (mlLral closes before Lhe
Lrlcuspld b/c hlgher pressures)

S2 heart sound = beglnnlng of ulasLole = pulmonlc and aorLlc close (varlaLlon wlLh resplraLlon
as dlaphragm goes down Lhey lncrease Lhe lnLraLhoraclc pressure. 8lood ls belng sucked lnLo
Lhe rlghL slde of Lhe hearL, and Lhe pulmonlc valve wlll close laLer Lhan Lhe aorLlc valve. So, Lhe
second hearL sound has a varlaLlon wlLh lnsplraLlon Lhe 2 separaLes away from A2 b/c more
blood comlng lnLo Lhe rlghL hearL, so Lhe valve closes a llLLle blL laLer.

S3 heart sound = no A S
and S2 = beglnnlng of dlasLole, obvlously, S3 = early dlasLole. S3 ls due Lo blood, ln early
dlasLole, golng lnLo a chamber LhaL ls volume overloaded. So, blood from Lhe lefL aLrlum ls
golng lnLo overloaded chamber, causlng Lurbulence, whlch ls Lhe S3 hearL sound. Cnly hear S3
heart sound |n vo|ume over|oaded chamber. lL could be from LPl (lefL venLrlcle overloaded)
8Pl S S lL means
volume overload ln Lhe chamber. Analogy: rlvers golng lnLo ocean leads Lo Lurbulence
(ocean ls Lhe venLrlcle wlLh a loL of fluld ln lL and Lhe rlver ls Lhe blood comlng ln durlng
dlasLole, Lhe rlver hlLs Lhls large mass of fluld ln Lhe venLrlcle, causlng Lurbulence and an S3
hearL sound).

S4 heart sound = laLe dlasLole Lhls ls when Lhe aLrlum ls conLracLlng and you geL Lhe lasL blL
S S e ls a
problem wlLh compllance. Compllance ls a fllllng Lerm.
So, . 1he lefL aLrlum ls
conLracLlng, Lrylng Lo geL blood lnLo a Lhlck venLrlcle, Lhe venLrlcle ls noncompllanL, and
Lherefore reslsLance wlll occur. 1hls wlll creaLe a vlbraLlon, leadlng Lo an S4 hearL sound. An
S4 heart sound |s due to a prob|em w|th comp||ance. 1he lefL aLrlum ls encounLerlng a
problem ln puLLlng blood ln laLe dlasLole lnLo Lhe lefL venLrlcle a
152

1
anymore
already overfllled chamber.

Summary: S||des:
vol overloaded? no S3. So can lL have an S4? ?es.

lf you have P1n, whlch Lype of hearL wlll you have? ConcenLrlc P?. So, ln P1n, whlch Lype of
hearL sound wlll you have? S4.

vol overloaded? ?es. So can lL have an S3? ?es, can lL also have an S4? ?es. Why can lL also
S 8 A all fllled up, buL always room
for deserL lll vlbraLlon LhaL occurs when lL fllls ls an S4 hearL sound. So you have boLh S3 and
S4 hearL sound = gallop rhyLhm (Lhey have S1, 2, 3, and 4).

Pow do you know lf lLs from Lhe lefL or rlghL? lL ls breaLhlng. When you breaLh ln, you are
sucklng blood Lo Lhe rlghL slde of Lhe hearL. A|| r|ght s|ded heart murmurs and abnorma|
heart sounds (|e S3, S4) |ncrease |n |ntens|ty on |nsp|rat|on Lhls ls more obvlous b/c Lhere ls
more blood ln Lhere, and lL emphaslzes Lhose abnormal sounds. rob geL Lhem on exp|rat|on
w|th pos|t|ve |ntrathorac|c pressures LhaL are helplng Lhe lefL venLrlcle push blood ouL of Lhe
hearL Lhls ls when abnormal hearL sounds and abnormal murmurs wlll lncrease ln lnLenslLy
on explraLlon. So, all you have Lo do ls flgure ouL LhaL Lhere ls an S3 hearL sound. *****1hen,
you have Lo flgure ouL whlch slde lL ls comlng from. Louder on explraLlon, Lherefore lLs from
Lhe rlghL slde.
Lxample: essenLlal P1n = lefL,
MlLral regurg = rlghL,
and MlLral sLenosls = mlddle.

III. Murmurs

Stenos|s = prob ln open|ng, LhaL ls when Lhe valve ls openlng, and LhaL ls when Lhe murmur
occurs.
kegurg|tat|on = prob ln c|os|ng Lhe valve, LhaL ls when Lhe valve ls closlng, and LhaL ls when
Lhe murmur occurs.

need Lo know where valves are heard besL rlghL 2
nd
lCS (aorLlc valve), lefL 2
nd
lCS (pulmonlc),
lefL parasLernal border (Lrlcuspld), apex (mlLral) necessarlly where Lhe valve ls, buL
where Lhe nolse ls heard Lhe besL.
A. Stenos|s:

153

1. Systo||c Murmurs:
Who ls open|ng |n systo|e = aort|c and pu|mon|c va|ves = Lherefore, murmurs of aorLlc
sLenosls and pulmonlc sLenosls are occurrlng ln sysLole. 1hls ls when Lhey are openlng, Lhey
have Lo push Lhe blood Lhrough a narrow sLenoLlc valve.

a. Aort|c Stenos|s Lv conLracLs and lL ls encounLerlng reslsLance - lnLenslLy of Lhe murmur
goes up, as lL ls pushlng and pushlng, lL geLs Lo a peak and Lhls ls dlamond shape conflguraLlon
Lhls ls why lL ls called an e[ect|on murmur. So, Lhey ofLen have dlagrams of Lhe
conflguraLlons on Lhese murmurs. WlLh an e[ecLlon murmur (aorLlc sLenosls), lL wlll have a
crescendo-decrescendo (hence, dlamond shaped conflguraLlon). So, wlLh aorLlc sLenosls,
Lhere ls an e[ecLlon murmur ln sysLole, heard besL aL Lhe rlghL 2
nd
lCS, whlch radlaLes Lo Lhe
caroLlds, and Lhe murmur lnLenslLy lncreases on explraLlon, and wlll probably hear an S4

b. u|mon|c Stenos|s heard besL on lefL 2
nd
lCS, e[ecLlon murmur, and lncreases on
explraLlon.

2. D|asto||c murmurs: ln dlasLole, mlLral and Lrlcuspld valves are openlng.

a. M|tra| Stenos|s (problem ln openlng Lhe valve) L P
Lhe problem, Lhe mlL
lefL venLrlcle. So, Lhe lefL aLrlum wlll geL sLrong b/c lL has an afLerload Lo deal wlLh lL
becomes dllaLed and hyperLrophled (Lhe aLrlum) whlch predlsposes Lo aLrlal flb, Lhrombosls,
and sLasls of blood. So, Lhe aLrlum ls dreadlng dlasLole b/c lL has Lo geL Lhe bulldup of blood
W
Lhe openlng snap. All Lhe blood LhaL was bullL up ln Lhe aLrlum comes gushlng ouL lnLo Lhe
venLrlcle, causlng a mld-dlasLollc rumble. So, you have an open|ng snap fo||owed by a
rumb||ng sound (due Lo excess blood gushlng lnLo Lv). WlLh mlLral sLenosls, Lhere ls a
problem wlLh openlng Lhe valve, and Lherefore you are under fllllng Lhe lefL venLrlcle, and
Lherefore wlll be no P? b/c you are under fllllng lL. lf you are havlng Lrouble geLLlng blood
lnLo lL, you are noL overworklng Lhe venLrlcle, Lhe lefL aLrlum has Lo do mosL of Lhe work.
Peard besL aL Lhe apex and wlll lncrease ln lnLenslLy on explraLlon. (same concept w|th
tr|cusp|d stenos|s, [ust a d|fferent va|ve).

8. kegurg|tat|on problem ln closlng Lhe valve.

1. Systo||c Murmurs: m|tra| and tr|cusp|d are c|os|ng |n systo|e.

a) M|tra| kegurg: lf Lhey are lncompeLenL and mlLral valve cannoL close properly. Lxample: 80
mls of blood = normal sLroke volume, leLs say 30 mls lnLo Lhe lefL aLrlum and only 30 mls
leaves Lhe aorLa. So, an exLra 30 mls of blood ln Lhe lefL aLrlum, plus Lrylng Lo flll up and have
154

excess blood Lhere way more blood ends up ln Lhe lefL venLrlcle and lL becomes vo|ume
over|oaded. So, how would Lhe murmur characLerlsLlcs be lf Lhere ls a problem ln closlng Lhe
valve? lL wlll noL be an e[ecLlon murmur, wlll [usL sound
as blood all Lhe way Lhrough sysLole ls golng Lhrough Lhe lncompeLenL mlLral valve, back lnLo
Lhe lefL aLrlum Lherefore lL ls pansysLollc or almosL pansysLollc
SomeLlmes, lL wlll obllLeraLe S1 and S2. So, |s an ap|ca| murmur, pansysto||c, S3 and S4 (b]c a
prob|em w|th comp||ance and vo|ume over|oad, |ncreased |n |ntens|ty on exp|rat|on.

b. 1r|cusp|d kegurg: lL wlll be pansysLollc, S3 and S4, lefL parasLernal border, and lncreases on
lnLenslLy on lnsplraLlon). Lxample: lvuA wlLh fever, pansysLollc murmur along parasLernal
border, S3 and S4 hearL sound, accenLuaLlon of Lhe neck velns, whaL ls Lhe mosL llkely dx?
lnfecLlve endocardlLls of Lrlcuspld valve, whlch ls Lhe MC lnfecLlon. So, lL was exLremely lmp Lo
know lf Lhe murmur lncreased on lnsplraLlon (whlch ls rlghL slded). lf Lhe quesLlon sald LhaL
Lhe murmur had lncreased on explraLlon, lL would be lnfecLlve endocardlLls of Lhe mlLral valve
(whlch ls lefL slded).

2. D|asto||c Murmurs: want the aort|c and pu|mon|c va|ves to c|ose (whaL you [usL pumped


Aort|c kegurg (as seen ln syphllls aneurysm buL Lhls ls due Lo Lhe sLreLchlng of Lhe rlng). ln
sysLole Lhe blood goes ouL and Lhe valve
blood wlll Lrlckle back ln. Lxample: 80 cc wenL ouL lnlLlally and 30 cc ls drlpped back ln. As
blood keeps drlpplng back ln, you wlll geL a vo|ume over|oaded chamber. LvenLually you wlll
have and Luv of 200 mls (lnsLead of 120). So, for aorLlc regurg, when you hear Lhe murmur?
AfLer Lhe 2
nd
LhaL makes Lhe
sound of a hlgh plLched blowlng dlasLollc murmur lnLo Lhe rlghL second lCS, lncreases ln
lnLenslLy on explraLlon, S3 and S4 hearL sounds, vol overloaded, and boundlng pulses. WhaL
valve leafleL ls drlpplng blood? AnLerlor leafleL of mlLral valve. 1hls ls one slde of Lhe ouLflow
LracL ouL of Lhe aorLa. WhaL murmur does LhaL creaLe? Aust|n f||nt murmur. lf you have
aorLlc regurg wlLh an AusLln fllnL murmur, you need Lo call Lhe cardlac surgeon. need Lo
replace Lhe valve b/c you are slgnlflcanLly drlpplng blood. 1herefore, Lhls murmur ls lmp b/c
when lL ls Lhere, you have Lo perform surgery.

IV. neart Ia||ure: Left or k|ght neart Ia||ure

LefL Pl = lungs and aroxysmal nocLurnal dyspnea/plllow orLhopnea

8lghL = Llver

A. Left heart fa||ure=forward fallure, canL geL blood ouL of Lhe hearL b/c Lhe Lv falls
155

1herefore your lefL venLrlcle has Lo push agalnsL an afLerload and falls, or lL has Lo deal wlLh

muscle buL now flbrous Llssue and Lhls reduces conLracLlllLy and lL falls. l llure
b/c you are havlng problems geLLlng blood ouLslde of Lhe hearL. 1hls means LhaL Luv wlll
lncrease b/c you cannoL geL all Lhe blood ouL b/c you cannoL push lL ouL. 1he pressure and
volume wlll go back ln Lo Lhe lefL aLrlum, back lnLo Lhe pulmonary vessels, lncrease Lhe
hydrosLaLlc pressure, and Lhen pulmonary edema. WlLh chronlc lefL hearL fallure, Lhls wlll lead
Lo 88C
spuLum. Cn cyLology, you wlll see hearL fallure cells, whlch are alveolar macrophages LhaL has
88C u|monary edema |s a|ways |eft
heart fa||ure. Left heart fa||ure |s a d|agnos|s of symptoms, b]c the ma|n symptom |n LnI |s
dyspnea (SC8), have troub|e breath|ng b]c f|u|d |n there.

8. k|ght neart Ia||ure: ulagnosls of slgns: 8ackward lallure, canL geL blood lnLo Lhe hearL.
8Pl ls a problem of Lhe rlghL hearL geLLlng blood Lhrough Lhe pulmonary vessels Lo Lhe lefL
hearL. So, lf lL falls, blood bullds up behlnd lL, and lL ls a backward fallure. 8/c lf lL cannoL geL
blood Lhrough pulmonary vessels lnLo Lhe hearL, blood wlll bulld up behlnd lL, and hydrosLaLlc
pressures wlll bulld ln Lhe venous clrculL. 1hls leads Lo neck veln dlsLenslon, also, wlll geL
hepaLomegaly (whlch ls palnful), and a nuLmeg llver b/c of Lhe lncreased pressures ln Lhe vena
cava are LransmlLLed Lo Lhe hepaLlc veln, whlch empLles lnLo lL, Lhen back lnLo Lhe llver and Lhe
cenLral veln, Lhen wlll geL red doLs all over llver, whlch looks llke a nuLmeg. MCC congested
hepatomega|y = knI. WhaL caused Lhe lncreased ln hydrosLaLlc pressure also golng Lo
produce plLLlng edema and posslbly asclLes Lherefore lLs more slgns Lhan lL ls sympLoms. So,
neck ve|n d|stens|on, p|tt|ng edema, hepatomega|y, nut meg ||ver, asc|tes.

C. Lxamp|es of LnI:
When you lle down Lo go Lo sleep, you can reabsorb up Lo 1 llLer of fluld b/c lL wlll go from Lhe
1
golng back Lo Lhe rlghL hearL and lnLo Lhe lefL hearL. Powever, whaL lf you had lefL Pl? 1here

hearL ls havlng Lrouble geLLlng blood ouL, wlLh even more blood comlng back ln. 1hen Lhe
hearL cannoL handle lL and goes back Lo Lhe lungs, leadlng Lo dyspnea and conLlnues for Lhe
nexL 30 mlnuLes Lhls ls paroxysma| nocturna| dyspnea. LvenLually lL seLLles down, you go
back Lo sleep, wake up agaln, and lL occurs agaln. L reallzes LhaL afLer you sLand up, Lhen lL
evenLually goes away Lherefore Lhey puL a plllow under Lhem Lo decrease Lhe dyspnea when
Lhey wake. 1hls ls called p|||ow orthopnea. lf lLs one plllow orLhopnea, lLs noL LhaL bad,
however, lf you have Lo slL up, you have serlous lefL hearL fallure b/c you are lmposlng gravlLy.
!usL by puLLlng head on one plllow wlll decrease venous reLurn back Lo Lhe hearL. lf you puL 2
plllows under, lL wlll decrease Lhe dyspnea even more b/c of effecLlve gravlLy. So, p|||ow
orthopnea and paroxysma| nocturna| dyspnea are s|gns of LLI1 heart fa||ure.
156


D. 1reatment:
lf you have hearL fallure (rlghL or lefL), whaL ls Lhe besL nonpharmacologlc LreaLmenL? 8esLrlcL
waLer and salL.

What the k|ng of kx of nI? ACL |nh|b|tor b]c |t decreases after|oad AND pre|oad at the same
t|me. ACL |nh|b|tors lncrease longevlLy by (1) decreased aldosLerone, Lherefore decreased salL
and waLer reabsorpLlon whlch decreases preload and (2) by blocklng AngloLensln ll, wlll lead Lo
a decrease ln vasoconsLrlcLor effecL on perlpheral reslsLance arLerloles, whlch wlll decrease
afLerload.

Ls wlLh sp|rono|actone + ACL |nh|b|tor dld beLLer b/c aldosLerone wlll evenLually break
Lhrough and become elevaLed agaln, Lherefore ACL lnhlblLor acLlng agalnsL aldosLerone ls noL
a permanenL suppresslon. So splronolacLone whlch speclflcally block aldosLerone, plus Lhe
ACL 1
splronolacLone and ACL lnhlblLor b/c lL wlll lncrease longevlLy.

L. n|gh output fa||ure
Cne cause ls endotox|c shock perlpheral reslsLance arLerloles are dllaLed, Lherefore an
lncrease ln C3a, C3a, nC, leadlng Lo lncreased venous reLurn Lo Lhe hearL and Lhe hearL
evenLually glves up. 1here are also many oLher
vlscoslLy/radlus Lo Lhe fourLh power. So, lf you vasodllaLe Lhe perlpheral reslsLance arLerloles,
and you decrease 18, more blood reLurns Lo Lhe rlghL hearL, Lhe lefL hearL has Lo deal wlLh lL,
Loo, and pL runs Lhe rlsk of hlgh ouLpuL fallure. So, one cause of Lhe vasodllaLaLlon ls sept|c
shock, whlle Lhe oLher ls th|am|ne def|c|ency. roblem ln Lhlamlne def: A1 depleLlon:
smooLh muscle cells and perlpheral reslsLance arLerloles need A1, Lherefore Lhey do noL work
as well, and Lhere ls vasodllaLaLlon of Lhe perlpheral arLerloles, leadlng Lo hlgh ouLpuL fallure.
So, Lhlamlne def can produce hlgh ouL puL fallure b/c vasodllaLaLlon of Lhose vessels.

l? hyperLhyroldlsm Lhyrold hormone lncreases Lhe synLhesls of beLa recepLors ln
Lhe hearL. CeL an lncrease ln force of conLracLlon, and more blood. SysLollc pressures are
hlgher, and go lnLo hlgh ouLpuL fallure.

AV f|stu|as le geL sLabled ln Lhe leg, and develop an Av malformaLlon, where Lhere ls
arLerlole blood bypasslng Lhe mlcroclrculaLlon golng dlrecLly Lo Lhe venous clrculaLlon and Lhe
blood comes back fasLer Lo Lhe hearL Lhan normal, a brulL can be heard over Lhe mass and lL
wlll be pulsaLlle, lf you press Lhe proxlmal porLlon of lL, hearL ra 8
Lhese are all slgns of Av flsLula, leadlng Lo hlgh ouLpuL fallure.

So, 3 examp|es of h|gh output fa||ure are endotox|c shock, graves, and AV f|stu|as
157


V. Congen|ta| heart dz
A. know feta| c|rcu|at|on (whlch vessels have Lhe leasL/mosL C
2
), remember LhaL Lhe baby ls
nC1 exchanglng blood wlLh C
2
ln Lhe lungs. ulmonary vessels ln Lhe feLus look llke Lhey have
pulmonary P1n Lhey are so Lhlck LhaL lL ls exLremely hard Lo geL blood Lhrough Lhe
pulmonary arLery lnLo Lhe Lv b/c very llLLle blood can go Lhere Lhls ls why baby needs a
paLenL ducLus Lo geL blood ouL. Where ls C
2
comlng from? Comlng from chorlonlc vlllus
P
dlpplng lnLo blood and exLracLlng C
2
from lL. Cbvlously, Lhls ls noL as good an C
2
source as Lhe
lungs, Lherefore, you wanL a hlgh afflnlLy Pb Lo be able Lo geL whaL llLLle C
2
ls down ln Lhe area
Lhls ls why bables have Pbl, b/c of lLs hlgh afflnlLy Lo grab C
2
from Lhe blood. 8ad news ls
LhaL lL geLs Lhe C
2
lL lefL shlfLs Lhe curve. WhaL ls
compensaLory response? 1hls lefL shlfL causes Llssue hypoxla, whlch wlll cause LC Lo be
released and Lhe kld wlll have an 18 gram Pb b/c of Lhls, all newborns (ln a sense) have
1 Pl C
2
88C P
and baby geLs more C
2
.

Crder of C
2
pass|ng: C
2
goes Lhrough syncyLloLrophoblasL of chorlonlc vlllus, lnLo Lhe
cyLoLrophoblasL, Lhen Lhrough Lhe myxomaLous sLroma of Lhe chorlonlc vlllus, Lhen lnLo Lhe
blood vessel. 1he blood vessels of Lhe chorlonlc vlllls all coalesce Lo form Lhe umb|||ca| ve|n.
1hls has Lhe h|ghest C
2
content. lL goes Lo Lhe llver and lL can go Lwo ways: 1) lnLo Lhe hepaLlc
slnusolds and recollecLs lnLo Lhe hepaLlc veln and geLs dumped lnLo Lhe lvC, and 2) ducLus
venosls and sLralghL lnLo Lhe lvC. 1hen lL goes up Lhe rlghL slde of Lhe hearL, Lhe foramen
ovale ls open ln all feLuses (lLs noL closed) so all Lhls blood ls comlng up Lhe lvC wlll lL go
sLralghL across, Lhrough Lhe foramen ovale and lnLo Lhe lefL aLrlum, or wlll lL go lnLo Lhe lvC
lnLo Lhe rlghL aLrlum, down Lo Lhrough Lhe Lrlcuspld valve, and lnLo Lhe rlghL venLrlcle? lL wlll
go Lhrough Lhe foramen ovale. So, all Lhls oxygenaLed blood wlll go dlrecLly from Lhe rlghL
aLrlum of Lhe foramen ovale lnLo Lhe lefL aLrlum, Lhen Lhe lefL venLrlcle and ouL Lhe aorLa.
WhaL abouL SvC blood valve? lL ls comlng from Lhe superlor parL of Lhe rlghL aLrlum (lLs noL
gonna make a lefL Lurn and go Lhrough Lhe foramen ovale). lL wlll go sLralghL down, Lhrough
Lhe Lrlcuspld valve lnLo Lhe rlghL venLrlcle. now, lL wlll go ouL Lhe pulmonary arLery. 1hls ls a
8C8LLM b/c Lhe pulmonary vessels are L
amounL of pressure. 1o counLer Lhls problem, kepL Lhe paLenL ducLus open (whlch ls kepL open
by Lhe CL2, a vasodllaLor, made by Lhe placenLa) so, Lhere ls a rlghL Lo lefL shunL and blood
can geL ouL of Lhe pulmonary arLery and dumped back lnLo Lhe aorLa. 1hen, when Lhe baby ls
born and Lakes lLs flrsL breaLh, Lhe pulmonary vessels (LhaL were all shuL), all open wlLhln a
mllllsecond, and blood ls golng Lhrough Lhose pulmonary arLerles and gas exchange ls
occurrlng Lhrough Lhe lungs ln llLerally seconds. Also, Lhe paLenL ducLus closes and forms Lhe
llgamenLum arLerlosum. 1hls ls normal feLal clrculaLlon. vessels wlLh Lhe leasL C
2
are Lhe 2
umblllcal arLerles, and Lhe one wlLh Lhe mosL amounL of C
2
ls Lhe umblllcal veln.
158


8. Shunts:
Look aL C
2
saLuraLlons (Lhls ls how Lhey dx Lhem Lhey caLheLerlze, measure C
2
saLuraLlons ln
dlfferenL chambers, and know whlch dlrecLlon Lhe shunLs are golng.

need Lo geL used Lo Lwo Lerms sLep up and sLep down.
lf you have a |eft to r|ght shunt, and have oxygenaLed blood golng lnLo unC
2

happenlng Lo C
2
saLuraLlon on Lhe rlghL slde? Step up b]c m|x|ng C
2
S-qb
2
S>I

lf you have a r|ght to |eft shunt wlLh unC
2
S>v-v-qb
2
S> d? Step down.
1he C
2
saLuraLlon on Lhe rlghL slde of Lhe hearL ln blood reLurnlng from Lhe body ls 73. 1he
C
2
saLuraLlon on Lhe lefL slde ls 93.

C. VSD (MC)
W - lefL or rlghL venLrlcle? LefL, Lherefore Lhe dlrecLlon of Lhe shunL ls lefL Lo
rlghL. So, oxygenaLed blood wlll be dumped lnLo Lhe rlghL venLrlcle, leadlng Lo sLep up. Also, lL
wlll pump lL ouL of Lhe pulmonary arLery, leadlng Lo sLep up. So, you have a sLep up of C
2
ln
rlghL venL and pul arLery. WhaL lf Lhls ls noL correcLed? WlLh Lhls mech, you are volume
overloadlng Lhe rlghL slde of Lhe hearL b/c of all LhaL blood comlng over. 1he ouLcome of Lhls
wlll be pu|monary n1N (Lhe pulmonary arLery has Lo deal wlLh more blood and musL conLracL
more leadlng Lo pul P1n) Cnce pul P1n occurs, rlghL venLrlcle wlll have a problem
conLracLlng and lL wlll geL hyperLrophled. Suddenly, you run Lhe rlsk of reverslng a shunL b/c
Lhen rlghL venLrlcle could evenLually be sLronger Lhan Lhe lefL. So, lL wlll be a rlghL Lo lefL shunL
Lhls ls called u&\&8? &\ . So, an uncorrecLed lefL Lo rlghL shunL has Lhe
L A
have cyanos|s M vSu eed Lo be
paLched.

D. ASD
normal for a feLus Lo have a paLenL foramen ovale, lL ls noL normal once Lhey are born. Whlch
dlrecLlon wlll blood go Lhrough Lhe foramen ovale? LefL Lo rlghL (b/c Lhe lefL slde ls always
sLronger Lhan Lhe rlghL). 1herefore, whaL wlll happen Lo Lhe rlghL aLrlum? Step up so lL wlll
go from 73 Lo 80. WhaL wlll happen Lo Lhe rlghL venLrlcle and pulmonary arLery? Step up.
So, what |s the ma|n d|ff |n C2 saturat|ons |n VSD vs ASD? ASD |s step up of C2 a|so |n the
r|ght atr|um. Are you volume overloadlng Lhe rlghL hearL? ?es. So do you run a r|sk for
-vS ? ?es. WhaL else are aL lncreased rlsk for? aradoxlcal embollzaLlon. WhaL lf
uv1 res of Lhe
rlghL slde of Lhe hearL are lncreaslng, and you have a paLenL foramen ovale wlll Lhere be an
embolus LhaL can go from Lhe rlghL aLrlum Lo Lhe lefL aLrlum and wlll have a venous cloL ln
159

arLerlal clrculaLlon? ?es Lhls occurs ln pLs wlLh ASu. MC teratogen that has ASD assoc|ated
w|th |t? Ieta| a|coho| syndrome (1]S000)

L. DA
l C
pulmonary arLery whlch ls sLronger? AorLa. So, oxygenaLed blood goes from lefL and geL
dumped ln Lhe pulmonary arLery before golng lnLo Lhe lungs. So, whaL happens ln Lhe
pulmonary arLery? SLep up. So, now lLs 80 C2 saLuraLlon the pu|monary artery |s the on|y
th|ng that has a step up of C2. 1hen wlll go under Lhe lungs and Lhe pulmonary veln wlll have
Lhe normal 93 C2 saL. 8/c Lhere ls an openlng beLween Lhese, Lhere ls blood golng back and
forLh durlng sysLole and dlasLole mach|nery murmur where ls lL heard besL? 8eLween
shoulder blades. Can you vol. overload Lhe rlghL hearL? ?es. ulmonary P1n? ?es. now whlch
W C
dumplng lnLo Lhe aorLa. Where does Lhe ducLus empLy? ulsLal Lo Lhe subclavlan arLery so,
Lhe baby wlll have plnk on Lop C
subclavlan arLery, Lherefore wlll have d|fferent|a| cyanos|s p|nk on top, cyanot|c on bottom.
WhaL ls Lhe LeraLogen assoc wlLh uA? CongenlLal 8ubella. lf you had a uA, can you close lL
off wlLhouL surgery? ?es. Pow? Indomethac|n - th|s |s a potent NSAID, wh|ch wou|d |nh|b|t
GL2, and Lherefore would sLarL consLrlcLlng and close on lLs own.

I. 1etra|ogy of Ia||ot
MC cyanoLlc congenlLal dz overrldlng aorLa: lLs sLraddllng Lhe sepLum,
pulmonlc sLenosls below Lhe valve, 8vP, membranous sepLal defecL (vSu). WhaL deLermlnes
wheLher you geL cyanosls or noL? uegree of pulmonlc sLenosls, noL all bables have cyanosls
and are acyanoLlc called acyanot|c tetra|ogy, why does Lhls occur? LeLs say Lhe degree of
pulmonlc sLenosls ls noL LhaL bad when Lhe rlghL venL conLracLs, a loL of Lhe blood goes up
C
probably wlll noL have cyanosls aL blrLh. WhaL lf lL was a severe sLenosls and when Lhe rlghL
venL conLracLs, very lll blood goL up Lhere? MosL wlll be shunLed rlghL Lo lefL and Lhere wlll be
a sLep uCWn ln C2 ln Lhe lefL venL and baby wlll be cyanoLlc. So, |t |s the degree of pu|mon|c
stenos|s that determ|nes whether you have cyanos|s or not. Whlch of Lhe groups of shunLs ls
cardlo-proLecLlve ln a pL wlLh LeLralogy of falloL? uA, ASu good leLs say Lhere ls an ASu,
C he rlghL aLrlum. 1hls
would cause a sLep up of blood lnLo Lhe rlghL aLrlum (Lhls ls good). Pow abouL a uA? LeLs
make belleve Lhls occurs C
C C C
and more geLs ouL good to have DA and ASD (foramen of ova|e) w|th tetra|ogy of fa||ot.

160

k|ght to |eft |eads to po|ycythem|a and a rea| r|sk for |nfect|ve endocard|t|s b/c shunLs golng
lnLo lefL slde, Lherefore can geL vegeLaLlons golng lnLo Lhe braln and oLher sysLemlc organs. A||
congen|ta| heart defects |ead to |nfect|ve endocard|t|s.

G. 1ranspos|t|on of Great vesse|s
L k Lhls noL Lhe case wlLh
LransposlLlon of greaL vessels
W n lL ls sLlll
geLLlng unoxygenaLed blood. lLs noL Lhe lefL aLrlum lL ls sLlll geLLlng 93 C2 saLuraLed blood
from Lhe pulmonary veln. 1he prob|em |s |n the ventr|c|es Lhe rlghL venLrlcle ls belng
empLled by Lhe aorLa, and Lhe lefL ls belng empLled by Lhe pulmonary arLery. So, Lhe Lhlng
LhaL ls Lransposed are Lhe venLrlcles (Lhe aLrla are flne). 1hls ls lncompaLlble wlLh llfe unless
vSu ASu uA P

SLarL aL Lhe aLrlal slde have 93 C2 comlng lnLo lefL aLrlum and lL ls golng from Lhe lefL Lo
rlghL, Lhere wlll be a sLep up of C2 ln Lhe rlghL aLrlum and Lherefore also a sLep up of C2 ln Lhe
rlghL venLrlcle. Some wlll go ouL Lhe aorLa and resL wlll go Lo Lhe lefL venLrlcle. 1hls ls good b/c
Lhe lefL venLrlcle ls belng empLled by Lhe pulmonary arLery, so Lhe blood wlll be Laken Lo Lhe
lungs Lo be oxygenaLed. So, Lhese shunLs are necessary. CLherwlse, Lhe rlghL venL belng
empLled by Lhe aorLa would be all oxygenaLed blood and Lhe lefL venLrlcle belng empLled wlLh
Lhe pulmonary arLery would noL be okay. So, by havlng Lhe shunLs, can geL around Lhese
A ASu C
rlghL aLrlum Lhere wlll be a sLep up of C2 ln Lhe rlghL venLrlcle, whlch ls belng empLled by Lhe
L 93 saLuraLed (maybe 80), and Lhls ls why Lhere ls cyanosls
ln Lhese paLlenLs. AL leasL some blood can geL ouL of Lhe aorLa and have some C2 Lo Lhe pL
and Lhey can survlve for a llLLle whlle. 8/c of Lhe rlghL Lo lefL shunL, LhaL blood ls belng
empLled by Lhe pulmonary arLery and LhaL ls golng Lo Lhe lungs and belng oxygenaLed. So, Lhe
S k nC1
vessels, buL a normal hearL on Lhe rlghL slde (called slnus lnversus).

n. Coarctat|on have preducLal and posLducLal
re = before paLenL ducLus, posL = afLer paLenL ducLus (afLer Lhe llgamenLum arLerlosum)
reducta| occur ln 1urner syndrome and go sLralghL lnLo fallure, Lherefore musL be correcLed
lmmedlaLely. ostducta| ar
adulL llfe. lmporLanL Lo recognlze b/c Lhey are a surglcally correcLable cause of P1n.
SLenosls ln aorLa whaL ls happenlng proxlmal? 1here ls Lrouble geLLlng blood Lhrough LhaL,
Lherefore Lhere wlll be a murmur heard besL beLween Lhe shoulder blades a sysLollc
murmur. 1here ls a loL of pressure bullL up proxlmally, so Lhe prox aorLa wlll be dllaLed and
Lhere wlll be a loL of pressure golng lnLo Lhe vessels Lhe subclavlan, lnLernal caroLlds
Lherefore Lhe 8 |n the upper extrem|t|es w||| be h|gher than |t |s |n the |ower extrem|t|es.
161

Also, wlLh lncreased blood flow lnLo Lhe braln, aL Lhe [uncLlon where Lhe communlcaLlng
branches hlL Lhe maln cerebral branches, we have no lnLernal elasLlc lamlna and no smooLh
muscle Lhere, Lherefore lL ls a weak area (for ALL people), Lherefore, everybody has the
potent|a| to deve|op berry aneurysms. WhaL would exacerbaLe, or make Lhe berry aneurysm
a reallsLlc Lhlng? n1N (any cause of P1n can cause berry aneurysms le Auku, essenLlal P1n,
Lhe boLLom llne ls P1n, and ALL hypertens|ve pts run the r|sk of berry aneurysms we all
have Lhe same defecL aL Lhe [uncLlon form any cause of P1n lLs noL unlque Lo Auku, lLs ln
all cases of P1n oLher relaLlons Lo P1n = subarachnold bleeds, sLreLch/dllaLaLlon of aorLlc
valve rlng and Lherefore a murmur of aorLlc regurg. All Lhe pressure on Lhe wall of Lhe
proxlmal aorLa can a|so pred|spose to d|ssect|ng aort|c aneurysm. WhaL ls dlsLal Lo Lhls?
uecreased blood flow, c|aud|cat|on (anglna of perlpheral vessels so when Lhey walk, Lhey
wlll geL calf paln, buLLock paln, Lhen Lhey sLop and lL goes away, Lhey walk lL hurLs) Lhls ls all
due Lo lschemla, and Lhe muscle developmenL Lo Lhe lower exLremlLles wlll noL be Loo good,
elLher. Muscle mass wlll be decreased, 8 dlfference beLween upper and lower exLremlLles,
and Lhe blood flow Lo Lhe renal arLerles ls decreased, leadlng Lo acLlvaLlon of Lhe 8AA wlll lead
Lo P1n. So Lhe n1N |n pts w|th Coarctat|on |s due to act|vat|on of kAA so lL ls a hlgh renln
P1n. So, lf you can correcL lL Lhe P1n wlll go away. When Lhere ls a problem (le a roadblock),
we have Lo go around lL le need collaLerals. Powever, Lhe aorLa ls noL a good place Lo have
a roadblock b/c only have Lwo ways Lo geL around Lhe block: 1)(raresL) superflclal eplgasLrlc
arLery, wlLh Lhe lnLernal mammary arLery can geL around Lhls, Lhls ls aL Lhe laLeral border of
hasselbach (Lhe superflclal eplgasLrlc arLery). So, when you sLlck your flnger ln Lhe canal and
have an lndlrecL lngulnal hernla. 8lghL Lhrough Lhe medlal slde wlll feel a pulsaLlon (where Lhe
sup eplgasLrlc arLery ls). 2) lnLercosLals on Lhe undersurface of Lhe rlbs and geLLlng exLra
blood Lhrough Lhem leadlng Lo notch|ng of r|bs (vlsuallzed on x-ray).

VI. Ma[or r|sk factors for coronary artery dz: know Lhe rlsk facLors!
Age ls Lhe mosL lmp rlsk facLor (cannoL conLrol) -43 for males, 33 for women why? Plgher
esLrogen levels, whlch affecL PuL levels. 8lsk facLor for CAu ls noL LuL, lLs PuL. PuL vlslLs faLLy
sLreaks, sucks LuL ouL, Lakes lL Lo Lhe llver Lo be meLabollzed. 33 ln women b/c LhaL ls Lhe age
of menopause, noL Laklng esLrogens and LhaL ls Lhe age when esLrogens go down, PuL levels
go down and rlsk goes up. lamlly hlsLory of premaLure arLery dz, clg smoklng, P, PuL<33,
dlabeLes, LuL (cholesLerol ls noL a rlsk facLor, LuL ls) b/c all LherapeuLlc declslons are based on
LuL levels, noL cholesLerol levels. PuL ls a negaLlve rlsk facLor: lf your PuL ls greaLer Lhan 60,
you can subLracL one from your ma[or rlsk facLor - le 38 y/o, buL PuL ls above 60, can subLracL
Lhe age rlsk facLor and wlll have no rlsk facLors.
VII. Ischem|c neart D|sease:
4 types: Ang|na, Myocard|a| Infarct, Sudden Card|ac Death Syndrome, Chron|c Ischem|c
neart D|sease

162

A. Sudden card|ac death syndrome = deaLh wlLhln Lhe lasL hr whaL wlll you see aL auLopsy?
Wlll nC1 see a coronary Lhrombus, wlll see severe coronary arLery aLherosclerosls. So, usually
Lhese pLs do noL have a Lhrombus, buL do have severe coronary arLery dz, leadlng Lo lschemla,
vC Ml
Lhere are no changes ln Lhe hearL (le pallor/CoagulaLlon necrosls), see severe coronary arLery
dz and dx sudden cardlac deaLh. very hlgh rlsk ln smokers.

8. Chron|c |schem|a heart dz l
arLery dz wlLh llLLle lnfarcLs, or had a small hearL aLLack, baslcally Lalklng abouL subendocardlal
lnfarcLlons. WhaL happens ls LhaL Lhe muscle geLs replaced by flbrous Llssue and evenLually
Lhe poor Lv ls all flbrous Llssue, wlLh no muscle Lherefore Lhe e[ecLlon fracLlon ls very low. lLs
0.2 lnsLead of Lhe normal 0.66 and Lhey dle from hearL fallure. llbrous Llssue does noL have
conLracLlllLy, Lhls dz ls Lhe 2
nd
MC lndlcaLlon for a hearL LransplanL.

C. Ang|na (MC type of heart dz)
3 types exert|ona|, pr|nzmeta|, unstab|e (rest|ng) ang|na

1. Lxert|ona| chesL paln on exerLlon, goes away wlLhln 3-10 mlnuLes of resLlng, S1
depresslon on LkC (1-2 mm depresslon) Lherefore a candldaLe for coronary anglogram Lo see


2. 4u&\>? seen ln women, occurs ln mornlng, due Lo vasospasm of Lhe coronary
arLerles, nC1 aLherosclerosls. ln some people, 1xA2 ls lmpllcaLed for Lhe vasospasm. S1
depress|on means subendocard|a| |schem|a. Coronary arLerles peneLraLe Lhe ouLslde of Lhe
hearL and go ln, so Lhe subendocardlal Llssue geL screwed b/c lLs furLheresL from Lhe blood
supply. 1herefore, wlLh coronary arLery aLherosclerosls, and decreased blood flow, who geLs
screwed? Subendocardlum and lL reacLs Lo lL wlLh paln and S1 depresslon. WlLh vasospasm of
coronary arLery, geL Lransmural lschemla Lherefore Lhere ls lschemla LhroughouL Lhe enLlre
Lhlckness of Lhe muscle S1 S S1
b/c Lransmural lschemla.

3. Unstab|e aka pre-lnfarcLlon anglna geL anglna on resLlng. Classlc hx: lnlLlally had sLable
anglna, now pL [usL geL lL when Lhey are slLLlng. 1hls means LhaL Lhey wlll need angloplasLy and
puL lnLo Lhe hosplLal. uo noL puL on Lreadmlll, Lhey wlll dle. WhaL velns do Lhey use?
Saphenous veln over 10 years wlll become arLerlallzed (lL wlll look exacLly llke an arLery). lf
you Lake a veln, and puL arLerlal pressures lnLo lL, lL wlll change lLs hlsLology and look exacLly
llke an arLery. 1hey have a hlgh Lendency for flbroslng off afLer 10 years b/c Lhey are velns.
l sed Lo Lhose
pressures. 1hey wlll remaln paLenL, buL cannoL do four vessel bypass wlLh one lnLernal
163

mammary arLery. So, Lhey use Lhe saphenous veln, whlch has Lhe Lendency Lo undergo flbrosls
over Llme b/c Lhey are arLerlallzed under pressure. 1hey can also use Lhe lnLernal mammary.


D. Acute MI
1 1A
problem wlLh Lhls b/c lL [usL breaks Lhe flbrln bonds Lo desLroy Lhe cloL. lL has a much blgger
problem wlLh Lhe breakdown of a venous cloL b/c Lhose have more flbrln. 1he
Lhromboses/cloLs ln Lhe hearL do noL have LhaL much flbrln. AnoLher facLor Lo deal wlLh ls
reperfuslon ln[ury C C
form, and a few of Lhe ln[ured myocardlal cells wlll dle. Cnce Lhose dle, lL wlll sLlll lmprove
longevlLy.

1. Comp||cat|ons of MI:
a) LAD coronary artery ls MC vessel Lhrombosed, and supplles enLlre anLerlor parL of your
lcular sepLum. So, Lhere wlll be paleness, wlLh
W A S
you have compleLe hearL block LhaL requlres ecLoplc pacemaker, whaL ls Lhe mosL llkely vessel
Lhrombosed? LAu. When you have LAu occluslon, you have c|ass|ca| s|gns pa|n rad|at|ng
the [aw, pa|n down the |eft arm, substerna| chest pa|n.

b) kCA = 2
nd
MC Lhrombosed arLery whlch supplles Lhe enLlre posLerlor parL of Lhe hearL and
Lhe posLerlor 1/3 of Lhe venLrlcular sepLum and Lhe enLlre rlghL venLrlcle. So, lL supplles Lhe
posL hearL, posL 1/3 of Lhe sepLum and Lhe enLlre rlghL venLrlcle. 1he mlLral valve has Lwo
valves wlLh paplllary muscles posLeromedlal paplllary muscle and posLeromedlo paplllary
muscle. So, whaL supplles Lhe posLerlor? 8CA. Also have Lhe SA node and Av node. 1he SA
node has an equal dlsLrlbuLlon beLween lefL and rlghL. Powever, Lhe AV node has a 9S
supp|y from the branches of the kCA Lhls brlngs up lnLeresLlng compllcaLlons. Lxample: pL
wlLh mlLral regurg murmur, whlch ls relaLed Lo posLeromedlal paplllary muscle dysfuncLlon, or
may break whaL ls Lhe problem? 1hrombosls of Lhe 8CA b/c Lhe 8CA supplles LhaL paplllary
muscle. So, mlLral regurg murmur LhaL occurs durlng Ml would be due Lo 8CA. If you knock
off the AV node, th|s |s s|nus bradycard|a, and atyp|ca| chest pa|n. 1he 8CA ls dangerous b/c
someLlmes pL wlll geL ep|gastr|c pa|n, whlch ls an aLyplcal paln. 1hls slmulaLes CL8u, le pL senL
home wlLh pepLo blsmol, and ends up dylng aL home (b/c of mlssed dx). 1hey should have
been senL Lo hosplLal. 1herefore, elderly pL wlLh ep|gastr|c pa|n cou|d be GLkD or coronary
artery thrombos|s of the kCA.
2. Gross]m|croscop|c features
need Lo know when Lhe hearL ls sofLesL and has a chance for rupLurlng Lhls ls beLween 3-7
days. When do you see gross manlfesLaLlon of belng a pale lnfarcL? 24 hrs begln seelng
paleness. CoagulaLlon necrosls ln 4-6 hrs.
164


Lxample: LAu Lhrombosls b/c see pale anLerlor 2/3 of hearL. 8upLure perlcardlum fllled wlLh
blood (hemoperlcardlum) mosL are lnLerlor, and Lherefore ls from Lhe LAu Lhrombosls how
does Lhls manlfesL lLself? uay 3 or day 4 complaln of chesL paln, have muffled hearL sounds,
neck veln dlsLenslon, and know Lhey have rupLured.

Lxample: rupLure of posL medlal paplllary muscle and lL was lnfracLed, Lherefore Lhe 8CA ls
Lhe cause
of Lhe rupLure so, whaL would Lhe murmur be? MlLral regurg Cn day 3 pL goes lnLo hearL
fallure, have a pansysLollc murmur, lncreases on explraLlon, and S3 and S4 hearL sound. lL
meanlng Lhe posLerlor medlal paplllary muscle was dysfuncLlonal
S
arlse beLween days 3-7. Wlll go lnLo hearL fallure b/c masslve volume overload and go rlghL
back Lo Lhe lungs.

Lxample: rupLure of anL wall
Lxample: rupLure of paplllary muscle, and Lhe posLeromedlal one ls MC
Lxample: Coag necrosls
Lxample: lnLervenLrlcular sepLum rupLures, Lherefore a lefL Lo rlghL shunL and a sLep up. MosL
lnLervenLrlcular rupLures are LAu Lhromboses.

Lxample: mura| thrombus (mural = wall) ln Lhls case, mural ls a Lhrombus, on Lhe wall. 1hey
are almosL always LAu Lhrombl b/c need a place Lo sLlck. WlLh anLerlor Ml, always glve asplrln
and puL pL on warfarln/heparln why do Lhey do LhaL? 1o prevenL mural Lhrombus from
formlng. So, when you have an anLerlor prob, Lhey wlll anLlcoagulaLe you. Mura| thromb| are
m|xed c|ots Lhey are noL a pure venous llke cloL or a plaLeleL llke cloL, Lhey are mlxed. P
how lL works: you have a Lransmural lnfarcLlon and Lherefore ln[ury Lo endoLhellal cells of Lhe
hearL, Lherefore plaLeleLs wlll sLlck so plaLeleLs are Lhe flrsL Lhlngs LhaL sLlck and Lhen b/c Lhe
muscle ls noL conLracLlng LhaL well (b/c lnfracLed muscle does noL conLracL), Lhere ls sLasls, and
C 88C
mlxed (plaLeleLs wlLh flbrln and venous cloL from sLasls). WlLh asp|r|n, you noL only prevenLlng
a coronary Lhrombus wlLh decreaslng plaLeleL aggregaLlon, buL also prevenLlng a mural
Lhrombus from lnlLlally formlng b/c lL lnhlblLs Lhe plaLeleLs from aggregaLlng. Also, by putt|ng
on warfar|n and hepar|n, you prevenL Lhe oLh u
Lhese b/c lL can embollze and Lherefore are very dangerous.

3. I|br|nous per|card|t|s can occur 2 Llmes ln a person wlLh Ml: 1) 1
sL
week geL a frlcLlon
rub, chesL paln (relleved when leanlng forward and worse when leanlng back - a 3 componenL
1 . And 2) hx
of Lransmural lnfarcL, comes ln 6 weeks laLer wlLh fever, muscle aches and palns, and a 3
165

componenL frlcLlon rub ln Lhe chesL = >? &\ / 0u0 u & u\\&
per|card|t|s W A
perlcardlal Llssue. 1hls Look 6 weeks Lo bulld up, and Lhey sLarL aLLacklng Lhe perlcardlum
leadlng Lo sysLeml u 1 2 types
are 1
st
week, not auto|mmune, and 6 weeks, auto|mmune. 8aslcally LreaL wlLh nSAluS.

4. Later comp||cat|ons ventr|cu|ar aneurysm
Lxample: pL 3 weeks ouL of Ml chesL bulges whaL under Lhere? Masslve pecLoralls ma[or
le systo||c bu|ge of per|card|um |s ventr|cu|ar aneurysm. 8lood ls collecLlng ln Lhe aneurysm
and maklng Lhe chesL bulge ouL. 1hls ls a laLe manlfesLaLlon
MC compllcaLlon ls nC1 rupLure, Lhls aneurysm ls llned by scar Llssue and Lherefore wlll noL
rupLure. MCC death |n a vent aneurysm = heart fa||ure. MosL of hearL has scar Llssue, whlch
leads Lo decreased e[ecLlon fracLlon, Lherefore, d|e of nLAk1 IAILUkL not rupture.

Lxample:AcuLe Ml lL ls f|brous t|ssue, wh|ch |s wh|ter and more patchy. llbrous
Llssue (scar) can be anywhere from 3 weeks Lo 10 years
M Ll Ll
probably wlll dle. lf you have a low Ll, you had a blg lnfarcL, wlLh a loL of muscle LhaL was
1 Ll l 8
lf your 0.4, le lLs very bad.

S. now do we dx MI? Ck-M8 |s dx of cho|ce
noL an LkC b/c lL has only an 80 senslLlvlLy showlng a new q wave, S1 elevaLlon. 1hey have
greaL speclflclLy: 1roponln l, Ck-M8 ls an lsoenzyme of creaLlnlne klnase have Ck-MM, M8,
and 88.

Ck M8 ls prlmarlly ln cardlac muscle. 1herefore, when you lnfarcL Lhe muscle, you wlll see a
prlmary lncrease ln cardlac muscle, and when Lhe muscle ls lnfracLed, wlll see an lncrease ln
LhaL enzyme. SLarLs Lo go up aL 6 hrs. eaks ln 24 hrs, and gone ln 3 days b/c lf Ck M8 ls
presenL afLer 3 days deflnes 8LlnfarcLlon. So, Lhe reappearance of Ck-M8 = 8LlnfarcLlon.

1ropon|n I elevaLes a few hrs earller Lhan Ck M8 lLs goes up aL abouL 4 hrs, and peaks ln
abouL 24 hrs, Loo. lL lasLs 7 days, whlch ls good. Powever, cannoL dx relnfarcLlon. So, afLer
day 3 1roponln wlll sLlll be Lhere and Lherefore, you cannoL dx relnfarcLlon. Ck-M8 replaces
LuP lsoenzymes.

LDn |soenzyme: normally, LuP2 ls hlgher Lhan LuP1. Powever, LDn1 |s |n card|ac musc|e.
So, when you have an lnfarcL, you release LuP1, and 1 becomes hlgher Lhan 2 whlch ls called
Lhe fllp. When you lnfarcL Lhrough Lhe muscle, 1 wlll be hlgher Lhan 2, and LhaL ls Lhe fllp. 1hls
occurs ln abouL 18 hours and peaks ln abouL 3 days and lasL for a week. MosL of Lhe Llme, we
166

use LuP enzymes lf Lhe pL came ln 2-3 days afLer sympLoms and Ck-M8 wlll have been gone by
Lhen. 1hen, look aL LuP lsoenzymes, and recognlze LhaL Lhere ls a fllp and reallze LhaL Lhere
was an Ml few days ago. 1hls wlll be replaced by 1roponln 1 b/c lLs elevaLed durlng Lhls Llme
perlod.

VIII. Va|vu|ar neart D|sease
A. M|tra| Va|ve ro|apse MC mlLral valve leslon more common ln women, Loo much valve
and looks llke a parachuLe (alr goes under a parachuLe and fllls lL up same wlLh blood)
blood wlll prolapse lnLo lefL aLrlum, and when lL sLops, lL causes a cllck. rolapse means LhaL
someLhlng ls comlng ouL le recLal prolapse.

So, wlLh mlLral valve prolapse, lL ls exLendlng lnLo Lhe lefL aLrlum. When lL sLops, and cannoL
go ln anymore, lL sLops and causes a cllck, and lL followed by a shorL mlLral regurg murmur. So,
openlng snaps occur ln mlLral and
Lrlcuspld sLenosls). WhaL ls Lhe paLhology? MyxomaLous degeneraLlon. WhaL CAC makes up
Lhe valve? uermaLan sulfaLe, Lherefore lLs an excess of dermaLan sulfaLe ln Lhe mlLral valve,
and lL becomes redundanL (Loo much of lL), blood goes under lL and causes a cllck and
murmur. ls lL closer Lo S1 or S2? lL deals wlLh preload. lf we lncreased vol of blood ln Lhe lefL
venLrlcle, Lhen Lhe cllck and murmur wlll come closer Lo S2 b/c lL Lakes longer for all Lhe evenLs
Lo geL blood ouL. lf we decrease Lhe amounL of blood comlng lnLo Lhe lefL venLrlcle (decrease
preload), Lhe cllck and murmur come closer Lo S1. So, when sLandlng and have Mv, whaL ls
preload vs. lylng down? lL ls less. Less preload = less blood ln Lhe venLrlcle = cllck and murmur
S n cllck and murmur closer Lo S2 b/c lncreaslng
preload. 1hey wlll ask: whaL wlll happen Lo cllck and murmur wlLh anxleLy? WhaL wlll happen
Lo hearL raLe wlLh anxleLy? lncrease. 1herefore, wlll have less Llme Lo flll venLrlcles, Lherefore
wlll come closer Lo S1.


C A


8. Aort|c Stenos|s
MC valvular cause of syncope wlLh exerclse
MCC anglna wlLh exerclse.
MCC mlcroanglopaLhlc hemolyLlc anemla

1hls wlll an e[ecLlon murmur, rlghL 2
nd
lCS, radlaLlon lnLo Lhe neck, sysLollc, lncreases ln
lnLenslLy on explraLlon. lnLenslLy of murmur wlLh dlfferenL poslLlons: whaL wlll lncrease Lhe
lnLenslLy of Lhe murmur (whaL wlll make lL worse and Lherefore louder)? lncreaslng preload ln
167

Lhe venLrlcle. WlLh decreased blood ln Lhe venLrlcle, lL wlll decrease Lhe lnLenslLy of Lhe
e[ecLlon murmur b/c lL has Lo go ouL Lhe sLenoLlc valve.
lf you are puLLlng more blood lnLo Lhe Lv and need Lo geL lL ouL, lL wlll lncrease Lhe lnLenslLy -
Lhls ls lmp b/c lL dlfferenLlaLes lL from hyperLrophlc cardlomyopaLhy.

Why do Lhey geL anglna wlLh exerclse? ulse ls dlmlnlshed and Lherefore Lhe sLroke volume
wlll decrease. So, when do Lhe coronary arLerles flll up? ulasLole. WlLh less blood Lhere (b/c

blood golng Lo Lhe hearL, leadlng Lo anglna. So, Lhls ls Lhe MC valvular leslon leadlng Lo anglna.
Also, wlLh syncope wlLh exerclse, b/c you have decreased cardlac ouLpuL, you wlll falnL.

C. M|tra| stenos|s
Sllde: 1hrombl, lefL aLrlum ls dllaLed, murmur |n d|asto|e (sLenosls prob ln openlng and Lhls
valve opens ln dlasLole, leadlng Lo snap and rumble), heard aL apex and lncreases ln lnLenslLy
on explraLlon.
MCC m|tra| stenos|s rheumat|c fever (acute). 8heumaLlc fever -vegeLaLlons, due Lo group A
beLa hemolyLlc sLrepLococcal lnfecLlon. usually occurs as posL-pharynglLls. As opposed Lo posL
sLrepLococcal glomerulonephrlLls, Lhls can be pharynglLls or a skln lnfecLlon. MosL of Llme
rheumaLlc fever ls from a prevlous LonsllllLls. When you culLure blood ln pLs wlLh rheumaLlc
fever, lL wlll be negaLlve. Wlll noL be able Lo grow Lhe organlsms b/c lLs noL an lnfecLlve
endocardlLls. lL ls an lmmunologlc mechanlsm. W|th strep, M prote|n |s the pathogen|c
factor for group A strep C A o Lhe hearL and [olnLs. So, when we
A A A
Llssue) Lherefore we aLLack our own hearL, [olnLs, basal ganglla and elsewhere. 1hls ls called
m|m|cry A A M
proLeln of Lhe bacLerla, so |ts |s a|| |mmuno|og|c! MC valve lnvolved ls Lhe mlLral valve. 1he
vegeLaLlons are sLerlle and llne along Lhe closure of Lhe valve. 1he vegeLaLlons usually do noL
embollze. know Iones cr|ter|a for dx of acute rheumat|c fever le young person, few weeks
ago had an exudaLlve LonsllllLls, now presenLs wlLh [olnL paln and swelllng and dyspnea, rales
ln Lhe lung, pansysLollc murmur, apex, and lncreases ln lnLenslLy on explraLlon, S3 and S4 hearL
sound due Lo acuLe rheumaLlc fever. ux ls rheumaLlc fever. MC symptom |s po|yarthr|t|s.
1hey llke Lhls quesLlon b/c ln chlldren, Lhere ls a llmlLed d]d for po|yarthr|t|s |t |nc|udes
[uven||e rheumat|c arthr|t|s, nenoch Schon|e|n purpura, rube||a, acute rheumat|c fever.
nowever, none of these have symptoms of heart fa||ure and m|tra| |nsuff|c|ency except for
acute rheumat|c fever. So, lf Lhey ask you Lhe MC valvular leslon ln acuLe rheumaLlc fever, lL ls
nC1 mlLral sLenosls. lL Lakes 10 years Lo have a sLenoLlc valve (mlLral sLenosls). So, Lhe
murmur LhaL you hear ls mlLral 8LCu8C, b/c all parLs of Lhe hearL are lnflamed, leadlng Lo
frlcLlon rub, myocardlLls (lnflamed myocardlum), and endocardlLls (Lhese are Lhe valves wlLh
Lhe vegeLaLlons). So, wlll geL mlLral regurg murmur wlLh acuLe rheumaLlc fever. CLher
feaLures of !ones crlLerla: [olnLs, cardlac abnormallLles, eryLhema marglnaLum (skln zlL),
168

subcuLaneous nodules (llke rheumaLlc nodules on Lhe exLensor surfaces Lhey are exacLly Lhe
same). 8h nodules and nodules assoclaLed wlLh acuLe rheumaLlc fever are exacLly Lhe same.
1 L !
S . Lxample: pL wlLh acuLe rheumaLlc fever (grade 3, pansysLollc,
apex, rales, S3 and S4, nodules, eryLhema marglnaLum) - S
chorea. ASC t|ter |s |mp, too #-S v -k- ->I Aschoff
nodules reacLlve hlsLlocyLes ln Lhe myocardlum, only flnd wlLh bx on deaLh. Summary:
lmmunologlc dz, wlll noL culLure ouL group A sLrep ln Lhe blood, !ones crlLerla (polyarLhrlLls,
MC S
le mlLral sLenosls, looklng from lefL aLrlum, down Lo Lhe venLrlcle looks llke a flshmouLh
(flshmouLh appearance).

Lxample: whaL ls Lhe mosL posLerlorly locaLed chamber of you hearL? LefL aLrlum. Seen besL
on Lransesophageal ulLrasound. 8/c lL ls posLerlorly locaLed, and enlarged when dllaLed, lL can
press on Lhe esophagus, leadlng Lo dsyphagla wlLh sollds (noL llqulds). Also, lL can sLreLch Lhe
lefL recurrenL laryngeal nerve and cause hoarseness. 1hls ls called v&?&\ .

Lxample: lf Lhey have an lrregular lrregular pulse, whaL does LhaL mean? Atr|a| f|br|||at|on.
uoes lL surprlse you LhaL Lhey geL Lhrombus ln Lhe lefL aLrlum? no. 8/c Lhere ls a loL of sLasls
b/c blood ls havlng Lrouble geLLlng Lhrough, leadlng Lo sLasls and Lhromboses. So, have Lo
anLlcoagulaLe Lhe pLs, whlch ls a bad combo.
ALrlal flb + Lhrombus = bad combo. When you plcLure A flb, lLs llke a vlbraLor and lll chlps can
come off and embollze Lhls ls very common ln paLlenLs wlLh Ml18AL S1LnCSlS.

MV valve ls belng prolapsed lnLo aLrlum, b/c lL ls so redundanL, and, chordae Lendlnae wlll
rupLure, leadlng Lo acuLe mlLral lnsufflclency. 1hls ls noL common ln Mv mosL of Lhe Llme lL
ls asympLomaLlc. MC sympLomaLlc Lhlng = palplLaLlons.
8&u?u0)<44)o&?&0>&>& drome. Marfan pL and pL dled
suddenly, why? nC1 dlssecLlng aorLlc aneurysm (do noL dle lmmedlaLely wlLh dlssecLlons geL
paln, radlaLlon and cardlac Lamponade) answer ls Mv and conducLlon defecLs. So, pt w|th
marfan and d|es sudden|y, th|s |s due to MV and conduct|on defects (not d|ssect|ng aort|c
aneurysm).

1r|cusp|d regurg know abouL lvuA wlLh lnfecLlve endocardlLls.

Carc|no|d syndrome ln order Lo have carclnold syndrome, musL have meLassls Lo llver of
carclnold Lumor. SeroLonln and Lhe Lumor nodules geLs lnLo hepaLlc veln LrlbuLarles and geLs
lnLo Lhe venous blood and baLhes Lhe rlghL slde of Lhe hearL, and seroLonln produces a flbrous
Llssue response of Lhe valves. So, wlll geL Lrlcuspld lnsuff and pulmonlc sLenosls. 1hese are Lhe
2 valvular leslons assoc wlLh carclnold syndrome. (1lS)
169


Ik. Infect|ve endocard|t|s
MlLral valve wlLh vegeLaLlons and rupLure chordae Lendlnae, vegeLaLlons are blg and bulky and
desLroylng Lhe valve (hence, lnfecLlve).
WhaL ls MCC? Strep v|r|d|ans, 2
nd
MCC = Staph
Whlle brushlng LeeLh, have a LranslenL sLrep vlrldlans lnfecLlon. lf you have an underlylng
cardlac dz, Lhen you run Lhe rlsk of developlng a bacLerlal endocardlLls b/c [usL brushlng your
LeeLh can cause lL Lo geL lnLo Lhe bloodsLream, wlLh damaged valves, lL can seed lnLo lL and
produce vegeLaLlons.
SLaph aureus can affecL a nC8MAL valve C8 a damaged valve.
MC valve lnvolved ln lnfecLlve endocardlLls = mlLral valve, 2
nd
MC valve = aorLlc valve
lf you are an lvuA (who ln[ecL lnLo velns), MC valve lnvolved = 1rlcuspld valve, 2
nd
MC ls aorLlc
1r|cusp|d |nvo|ved = Murmur of Lrlcuspld regurg, pansysLollc, lncreased on lnsplraLlon
Aort|c va|ve |nvo|ved: aorLlc regurg, hlgh plLched dlasLollc afLer S2
SLaph ls #1 (MCC) for lvuA
lf you have co|on cancer]u|cerat|ve co||t|s (any Lype of ulceraLlon of Lhe colonlc mucosa),
Lhere ls a unlque Lype of lnfecLlve endocardlLls Lhls ls strep bov|s = group D strep
>->-qSq>-kq>- |e UC or co|on
cancer. n|story of co|on cancer and have |nfect|ve endo organ|sm |s strep bov|s (not
staph).
AorLlc valve close relaLlonshlp of membranous porLlon of Lhe sepLum wlLh Lhe aorLlc valve.
So, why dld pL geL vegeLaLlons of Lhe aorLlc valve? 8/c Lhey goL vSu LhaL was noL plcked up. lf
you have congenlLal hearL dz, you have an lncreased rlsk for lnfecLlve endocardlLls. vSu LhaL
someone dld noL plck up caused aorLlc valve Lo geL lnfecLlve and cause aorLlc regurg.
1herefore, on Lhe LesL, wlll be mlLral valve lnfecLlve endo, or aorLlc lnfecLlve endo wlLh a vSu.
S 8oLh spoL
(red wlLh whlLe cenLer [usL llke kopllk spoLs ln measles, whlch are red wlLh a whlLe cenLer).
1hls ls why lL ls called Lhe kopllk spoL of Lhe eye. WhaL do Lhey all have ln common (aslde from
S C
[aneway leslons, 8oLh spoLs, and glomerulonephrlLls? A|| are type III n. All Lhese leslons are
lmmune complex vascullLls.
v AnA dx? L|bman sacs
endocard|t|s pt has Lupus (Llbman sacs ls noL Lhe MC leslon of Lhe hearL wlLh Lupus
perlcardlLls ls), Llbman sacs ls Lhe 2
nd
MCC, whlch ls flbrlnold necrosls llke rheumaLlc fever.
MaranLlc vegeLaLlons ln mucous secreLlng colon cancer = araneoplasLlc syndrome (lL ls
maranLlc endocardlLls ln a pL wlLh colon cancer). AcuLe rheumaLlc fever looks llke lL.
k. Myocard|t|s vs. er|card|t|s
Cn Lhe LesL, lf you have an lnfecLlon quesLlon, lL ls Coxsack|e v|rus.
MCC of myocardlLls and perlcardlLls,
MCC vlral menlnglLls = Coxsackle vlrus.
170

Cause of hand, fooL and mouLh dz? Coxsackle vlrus
P C
Lxample: L wlLh hearL fallure dld an endomyocardlal bx and lL had lymphocyLlc lnfllLraLe ln
C 1o dx, need Lo do a bx of subendocardlal
Llssue, and wlll see lymphocyLlc lnfllLraLe (as expecLed wlLh An? vlrus). 1herefore, le, pL ln
C

ChesL x-ray see waLer boLLle conflg Lhls pL as muffled hearL sounds (cannoL hear anyLhlng),
when Lhe pL breaLhs ln, neck velns dlsLend (shouldn
lncrease neg lnLraLhoraclc pressure, Lhe neck velns should collapse on lnsplraLlon), radlal pulse
ls decreased on lnsplraLlon, when you Lake 8 Lhere ls a drop of 10mmPg durlng lnsplraLlon.
ux? er|card|a| effus|on
WhaL 8 W k .
WhaL ls Lhe drop of 10 mm Pb on lnsplraLlon? u|sus paradoxus. Pow does all Lhls occur? 8/c
Lhere ls an effuslon of Lhe perlcardlal sac, meanlng LhaL LhaL hearL cannoL flll up (b/c Lhere ls
fluld around lL) leadlng Lo muffled hearL sounds. So, when you breaLh ln and blood ls
supposed Lo geL lnLo Lhe rlghL slde of your hearL, lL cannoL expand. So, Lhe neck velns dlsLend
k lgn. WhaL ever happens Lo rlghL slde of Lhe
hearL affecLs Lhe lefL slde of Lhe hearL b/c Lhe lefL slde recelve blood from Lhe rlghL slde. So,
Lhere ls no blood golng lnLo Lhe rlghL hearL, and Lherefore, no blood ls golng ouL of Lhe lefL
hearL, elLher. So, on lnsplraLlon, blood cannoL geL ouL of lefL slde (b/c blood ls noL comlng ouL
of Lhe rlghL hearL), leadlng Lo a drop ln pulse hence pu|sus paradoxus. Always see Lhese
Lhlngs LogeLher: neck veln dlsLenslon, drop ln pulse magnlLude, and drop ln 8, kus
slgn, pulsus paradoxus = per|card|a| effus|on. Powever, Lhls ls noL whaL Lhey wlll ask you
Lhey wlll ask whaL |s f|rst step |n management? Lchocard|ogram shows LhaL Lhey have fluld
(proves lL b/c need Lo call surgeon Lo do perlcardlocenLesls).
WhaL |s |t MC due to? er|card|t|s. What |s the MCC per|card|t|s? Coxsack|e.

W AnA L
Any young woman LhaL has an unexplalned perlcardlal or pleural effuslon ls lupus unLll proven
oLherwlse. Why? SeroslLls = lnflame serosal membranes lLs gonna leak fluld, leadlng Lo
effuslons. And ls a feaLure of Lupus.
L. Constr|ct|ve per|card|t|s
ln Lhlrd world counLrles, 18 ls MC. ln uSA, due Lo prevlous cardlac surgery b/c have Lo go
Lhrough perlcardlum. Sllde of a hearL and Lhlckened perlcardlum, no fluld, so when you
breaLhe ln blood goes Lo rlghL hearL, fllls up and hlLs wall called per|card|a| knock Lherefore
to d|fferent|ate per|card|a| effus|on from constr|ct|ve per|card|t|s, have muff|ed heart sounds
|n effus|on w|th no knock |n per|card|a| effus|on, and |n have some f||||ng up w|th a
per|card|a| knock |n constr|ct|ve per|card|t|s. WhlLe sLuff ln perlcardlum ls dysLrophlc
calclflcaLlon, and can see lL on x-ray. L goes Lo 8ussla and geLs dlarrhea = glardlasls)
171



kI. Card|omyopath|es
Large lefL venLrlcle and rlghL venLrlcle

A. Congest|ve card|omyopathy (aka d||ated card|omyopathy) Lxample: woman 6 weeks
posLparLum, and do a chesL x-ray and she has a generallzed cardlomegaly hearL ls huge, has
effuslons aL boLh lung bases dx? CongesLlve cardlomyopaLhy, Lhls ls a dz of Lhe cardlac
muscle and has many causes. L has boLh lefL and rlghL hearL fallure. Causes: 6 weeks
C MCC due
Lo congesLlve cardlomyopaLhy. CardloLoxlc drugs daunorublcln, Lrlcycllcs = drug lnduced
cardlomyopaLhles = congesLlve cardlomyopaLhy. Alcohollc wlLh blg hearL due Lo Lhlamlne def
= congesLlve cardlomyopaLhy.

8. nypertroph|c card|omyopathy
MCC sudden deaLh ln a young aLhleLe = hypertroph|c card|omyopathy. 1hlckness of sepLum
very Lhlck wlLh an asymmeLrlc P?, why? 8/c Lhe lnLervenLrlcular sepLum ls Lhlcker. 8lood
flow of lefL venL goes Lhrough narrow openlng (anL leafleL of mlLral valve so, lf you have
aorLlc regurg, blood wlll hlL anLerlor leafleL of mlLral valve and produce AusLln fllnL murmur).
Why ls Lhls a narrow openlng? 8/c lL ls Loo Lhlck. lf we Look a laser Lo burn lL off, could open lL
up, so, where ls Lhe obsLrucLlon ln hyperLrophlc cardlomyopaLhy? lLs noL aL Lhe level of Lhe
aorLlc valve, buL below lL. Why does lL obsLrucL? venLurl phenomenon Lhlngs go Lhrough a
narrow openlng qulckly and Lhere ls a negaLlve pressure behlnd lL. When blood, under
lncreased force of conLracLlon ls forced Lhrough, Lhe negaLlve pressure behlnd lL sucks Lhe
anLerlor leafleL behlnd Lhe sepLum and sLops Lhe blood, leadlng Lo obsLrucLlon of blood flow.
WhaL can we do Lo make Lhls beLLer (whaL can we do Lo reduce Lhe lnLenslLy of Lhe murmur
and have Lhe pL have beLLer CC)? uL more blood lnLo Lhe venLrlcle lncrease preload and
decrease obsLrucLlon b/c lL would pull lL away b/c Lhere ls more blood ln lL. All Lhese Lhlngs
LhaL lncrease preload wlll make Lhe lnLenslLy of Lhe murmur less and lmprove Lhe pL. So, lf you
are sLandlng up, wlll LhaL lmprove Lhe dz? no, b/c would decrease preload, leadlng Lo a harsh
sysLollc murmur. Powever, lf lylng down, Lhere ls lncreased venous reLurn Lo Lhe rlghL hearL,
and lncreased blood ln Lhe venL, Lhls would decrease lnLenslLy of murmur. ulglLalls would be
conLralndlcaLed b/c lL would lncrease force of conLracLlon, make lL go fasLer and make lL
obsLrucL qulcker. A beLa blocker would be good, Ca channel blocker would also be good b/c lL
would decrease force of conLracLlon, slow Lhe hearL raLe, and lncrease preload. 1hls ls MCC
sudden deaLh ln a young aLhleLe. lf you Look a secLlon of Lhe sepLum, lLs noL a normal sepLum
lLs dlsorganlzed, and Lhe conducLlon bundles are messed up, leadlng Lo conducLlon defecLs -
wlLh conducLlon defecLs, run Lhe rlsk of v. Lach and deaLh aL any Llme. 1hls abnormal
conducLlon sysLem and asymmeLrlc sepLum ls responslble. le 16 y/o bball player LhaL dled
172

suddenly whaL do you see aL auLopsy? PyperLrophlc cardlomyopaLhy. Mech? Abnormal
conducLlon

C. Lndocard|a| I|broe|astos|s (le of resLrlcLed cardlomyopaLhy)
lf lL ls resLrlcLlve, someLhlng ls prevenLlng Lhe venLrlcle from fllllng up. 1hls ls Lhe MC dz
causlng resLrlcLlve cardlomyopaLhy ln chlldren, and ls called endocardlal llbroelasLosls. 1hls dz
ls Lhe MC reason why a chlld needs a hearL LransplanL. lf Lhe chlld does noL geL a LransplanL,
Lhey wlll dle. CLher causes of resLrlcLlve cardlomyopaLhy l

D. Card|ac myxoma
83 ln Lhe lefL aLrlum, 13 ln rlghL
89, movable can move over and block orlflce of mlLral valve, leadlng Lo syncope. 1hey can
embollze (Lhey are very sofL and have blLs and pleces lnslde Lhem). Pave a loL of [unk lnslde
Lhem, whlch leaks ouL. lL can lead Lo fever, and oLher slgns and sympLoms. Syncope cannoL
flgure lL ouL, Lhen geL a Lransesophageal ulLrasound and see lL. So, Lhls ls Lhe MC pr|mary b9
tumor of the heart |n adu|ts.

1hey descr|be tumor |n heart of k|d Lhls ls rhabdomyoma (b9 Lumor of cardlac muscle)
Lhey are assoc wlLh auLo dom. dz, whlch one? 1uberous sc|eros|s. So, lf Lhey Lalk abouL a
CPlLu
more llkely ln a chlld wlLh Luberous sclerosls.





CnA1Lk 8: kLSIkA1Ck

I. A-a grad|ent know how to ca|cu|ate:

Alveolar C2 and arLerlal pC2 are never Lhe same. 1he dlfference beLween Lhe Lwo ls called
alveolar arLerlal gradlenL. 8easons for lL: (1) venLllaLlon and perfuslon are noL evenly
maLched ln Lhe lungs. When sLandlng up Lhe venLllaLlon ls beLLer Lhan perfuslon ln Lhe
apex, whereas perfuslon ls beLLer Lhan venLllaLlon aL lower lobes. 1hls explalns why almosL
all pulmonary lnfarcLlons are ln Lhe lower lobes perfuslon ls greaLer Lhere. Also, Lhls
explalns why reacLlvaLlon 18 ls ln Lhe apex 18 ls a sLrlcL aerobe and needs as more C2,
and Lhere ls more venLllaLlon ln Lhe upper lobes (hlgher C2 conLenL). normally, alveolar C2
ls 100 and Lhe arLerlal pC2 ls 93. So, normally, Lhe gradlenL ls 3 mmPg. As you geL older,
Lhe gradlenL expands, buL noL LhaL much. MosL people use Lhelr upper llmlL of normal ln
oLher words, have a very very hlgh speclflclLy of 30 mmPg. lf you have an A-a grad|ent of
173

30 mmng or h|gher there |s a prob|em. lL ls very hlgh speclflclLy (aka v Lruly have
someLhlng wrong). 1he concepL ls easy you would expecL Lhe gradlenL bLwn Lhe alveolar
C2 and Lhe arLerlal C2 Lo be greaLer lf you have pr|mary |ung dz. WhaL wlll do Lhls?
venLllaLlon defecLs (produces hypoxemla, and Lherefore prolongs Lhe gradlenL dropplng
Lhe C2 and subLracLlng, and Lherefore a greaLer dlfference bLwn Lhe Lwo), perfuslon
defecL (le pul embolus), and dlffuslon defecL. 8uL Lhe depresslon of Lhe medullary resp
cenLer by barblLuraLes does noL cause a dlfference ln A-a gradlenL. So, pro|onged A-a
grad|ent te||s you the hypoxem|a |s due to a prob|em |n the |ungs (vent
perfus|on]d|ffus|on defect). A norma| A-a grad|ent te||s you that someth|ng outs|de the
|ungs that |s caus|ng hypoxem|a (resp ac|dos|s |n resp ac|dos|s, C2 w||| go down).
Causes of resp acldosls: pulmonary probs (CCu), depresslon of resp cenLer (obsLrucL
upper alrway from eplgloLLlLls, larygloLracheobronchlLls, cafe coronary (paralyzed muscles
of resp), Culllaln 8arre syndrome, amyoLrophlc laLeral sclerosls, and paralysls of dlaphragm.
1hese all produce resp acldosls and hypoxemla, buL Lhe A-a gradlenL wlll be nC8MAL). So,
prolonged A-a gradlenL, someLhlng ls wrong wlLh Lhe lungs. lf A-a gradlenL ls normal, Lhere
ls someLhlng Cu1SluL of Lhe lungs LhaL ls causlng a resp problem.

lew Lhlngs musL always be calculaLed: anlon gap (wlLh elecLrolyLes) and A-a gradlenL for
blood gases all you need Lo do ls calc alveolar C2. We can ca|cu|ate the A-a grad|ent =
0.21 x 713 = 130 (0.21 ls Lhe aLmospherlc C2, and 760 mlnus Lhe waLer vapor=713). So,
1S0 m|nus the pCC2 (glven ln Lhe blood gas) d|v|ded by 0.8 (resp quoLlenL). So, normal
pCC2 = 40, and 40/.8=30 and 130-30 = 100, so, now LhaL l have calc Lhe alveolar C2, [usL
subLracL Lhe measured arLerlal pC2 and you have Lhe A-a gradlenL. 1hls ls very slmple and
glves a loL of lnfo when worklng up hypoxemla.

II. Upper kesp|ratory D|sease:

A. Nasa| o|yps:
3 dlff Lypes of nasal polyps MC ls an allerglc polyp. never Lhlnk of a polyp ln Lhe nose
of kld LhaL ls allerglc as an allerglc polyp. Allerglc polyps develop ln adulLs afLer a long
Lerm allergles such as allerglc rhlnlLls Lxample: 3 y/o chlld wlLh nasal polyp and resp
defecLs, whaL ls Lhe flrsL sLep ln managemenL? SweaL LesL b/c lf you have a polyp ln
Lhe nose of Lhe kld, you have cysLlc flbrosls

8. 1r|ad Asthma Lake an asplrln or nSAlu, have nasal polyps and of course have asLhma.
1 1he asplrln or nSAlu
ls Lhe answer buL Lhls ls how Lhey wlll ask Lhe quesLlon: 33 y/o woman wlLh chronlc
headaches or flbromyalgla. L has some Lype of chronlc paln syndrome and wlll noL Lell
you LhaL Lhe pL ls on medlcaLlon, and she develops occaslonal bouLs of asLhma whaL ls
8 nSAlu W
174

she has a polyp and LhaL she ls on an nSAlu, however, lf a pL ls ln paln or has chronlc
paln, lL ls safe Lo assume Lhe pL ls on paln medlcaLlon (le an nSAlu, MoLrln or asplrln).
Mech of asLhma from paln medlcaLlon: whaL do asplrln/nSAlus block? CCx, Lherefore
arachldonlc acld cannoL forms Cs buL Lhe Llpoxygenase paLhway ls lefL open. Some
people are very senslLlve Lo Lhls and L1 C4, u4, and L4 are formed, whlch are poLenL
bronchoconsLrlcLors, leadlng Lo asLhma. lL ls nC1 a Lype l P? rxn. lL ls a chemlcal
medlaLed non Lype l P? rxn. So, chron|c pa|n can |ead to asthma b]c of asp|r|n
sens|t|v|ty.

AnoLher assumpLlon you have Lo make: any well bullL male on anabollc sLerolds (le
fooLball player, wresLler) wlLh lnLraperlLoneal hemorrhage produce benlgn llver cell
adenomas whlch have Lhe Lendency of rupLurlng.

C. Laryngea| carc|noma (a squamous ce|| carc|noma)
ConcepL of synerglsm: MCC = Smoklng, 2
nd
MCC = alcohol
Alcohol and smoklng have a S?nL8ClS1lC effecL whlch leads Lo laryngeal carclnoma.
Lxample: leslon ln Lhls sllde ls a laryngeal speclmen whlch of Lhe followlng have Lhe
greaLesL rlsk facLor? Answer a|coho| AND smok|ng (Lhls ls Lrue for any squamous
cancer from Lhe esophagus Lo Lhe mouLh Lo Lhe larynx). Smoklng = MCC cancer ln
mouLh, upper esophagus and larynx. Alcohol can do Lhe same Lhlng, so lf you are
smoker and alcohol consumer, you can double your rlsk. MC sympLom assoc =
hoarseness of Lhe LhroaL.

Lxample: eplgloLLls, whaL can lnfecL lL? P. lnfluenza whaL ls Lhe sympLom? lnsplraLory
sLrlder. Lxample: 3 monLh old chlld dled wlLh lnsplraLory sLrlder dx? Croup
paralnfluenza, Lhls ls a 18ACPLAL lnflammaLlon. Whereas eplgloLLlLls ls elsewhere.
8oLh produce upper alrway obsLrucLlon.

175

III. kesp|ratory D|stress Syndromes:

A. nya||ne membrane dz (Neonata| kesp d|stress syndrome)
lf someLhlng has a loL of plnk ln lL, whaL ls lL? Pyallne
key Lo undersLandlng Lhls dz ls masslve aLelecLasls

1. What |s ate|ectas|s? Collapse of alrways. Why dld Lhese alrway collapse? no
surfacLanL (aka leclLhln/phosphoLldyl chollne/phosphoLldyl glycerol Lhey are all
surfacLanL). So, deflclenL of surfacLanL causes aLelecLasls b/c:
Co||aps|ng pressure |n the a|rways = surface tens|on]rad|us of a|rway. So, on
explraLlon, normally Lhe alrway wlll be smaller b/c Lhere ls a pos lnLraLhoraclc pressure.
lf you decrease Lhe radlus, you wlll lncrease Lhe collapslng pressure ln Lhe alrways.
1herefore, on explraLlon (ln all of us), we have Lo decrease surface Lenslon (whlch ls
whaL surfacLanL does) by dolng Lhls, lL keeps Lhe alrways open on explraLlon,
prevenLlng aLelecLasls.

2. 1hree causes of kDS:
a. remaLurlLy: surfacLanL beglns syn early, buL lL peaks aL 32-33 week, so lf you are
born premaLurely, you wlll noL have enough surfacLanL, and baby wlll develop
lncreased rlsk of developlng 8uS. SomeLlmes moLher has no cholce and musL
dellver baby, or else lL wlll dle, and Lhere ls someLhlng you can do Lo Lhe mom so
Lhe baby has more surfacLanL: glve moLher glucocorLlcolds b/c Lhey sLlmulaLe
surfacLanL synLhesls. Lxample: whaL can you do Lo lncrease surfacLanL (buL
Lhyroxlne (Lhyrold hormone)
(as does prolacLln), does LhaL mean you glve Lhyroxlne b4 dellverlng Lhe baby?
no, wlll glve mom and baby hyperLhyroldlsm.

b. ulabeLes
pregnanL, and Lhen obLalns glucose lnLolerance afLer dellvery so lf a dlabeLlc
geLs pregnanL, Lhls ls noL called gesLaLlonal dlabeLes, buL a dlabeLlc LhaL goL
pregnanL. lLs lmp LhaL a woman ln pregnancy has good glucose conLrol b/c lf she
ls hyperglycemlc, baby wlll be, Loo. 8/c baby ls hyperglycemlc, lL wlll sLlmulaLe
lnsulln synLhesls, and lnsulln has a negaLlve effecL on surfacLanL syn and wlll
decrease lLs synLhesls.

c. C secLlon b/c Lhe baby ls noL dellvered vaglnally, Lhere ls no sLress. 8/c Lhe baby
has noL been sLressed, Lhe AC1P and corLlsol are noL released, and surfacLanL ls
noL made. Whereas a chlld LhaL ls dellvered vaglnally has a loL of sLress and
Lherefore a loL of AC1P and corLlsol ls belng released, whlch sLlmulaLes surfacLanL
release. So, C secLlon predlsposes Lo 8uS.
176


So, Lhese are Lhe Lhree maln causes (premaLurlLy, dlabeLes, and C secLlon).


3. Comp||cat|ons and assoc|ated cond|t|ons:
a. Lxample: why are Lhe bables of poor glycemlc conLrol blg (macrosomlal)? 1he
l wlll lncrease sLorage of
Lrlglycerlde ln adlpose (lL lncreases faL sLorage). Where ls mosL of Lhe adlpose
locaLed? CenLrally. So, one of Lhe reasons why Lhey have macrosomla ls b/c lnsulln
sLlmulaLes synLhesls of 1C and deposlLlon of faL. Also, lnsulln lncreases upLake of
S S the
reason for macrosom|a |s |ncreased ad|pose and musc|e mass, both due to |nsu||n.
1hls also explalns why Lhey geL hypoglycemla when Lhey are born. 1he mo
hyperglycemla ls comlng lnLo Lhe baby, causlng Lhe baby Lo release lnsulln, Lhe
momenL lnsulln ls made and Lhe cord ls cuL, and no more lncrease ln glucose, glucose
goes down, and leads Lo hypoglycemla.

b. Superoxlde free radlcal damage seen ln reLlnopaLhy of premaLurlLy and bllndness
and bronchopulmonary dysplasla.

c. Why do bables wlLh 8uS commonly have uA? 8/c Lhey have hypoxemla. When a
normal baby Lakes a breaLh, lL sLarLs Lhe process of funcLlonal closure of Lhe ducLus.
Powever, wlLh hypoxemla afLer Lhey are born, lL remalns open, and Lhey have a
machlnery murmur.

d. Pyallne membranes are due Lo degeneraLlon of Lype ll pneumocyLes and leakage
of flbrlnogen, and lL congeals Lo form Lhe membrane. So, Lhey wlll glve a classlc
hlsLory for 8uS, and Lhen wlll ask for Lhe paLhogenesls of hypoxemla ln Lhe baby.
1hls ls a masslve venLllaLlon defecL b/c everyLhlng ls collapslng. 1hls ls a SPun1
problem, whlch leads Lo a masslve lnLerpulmonary shunL. 8x=LL Lherapy
poslLlve end exp pressure b/c Lhese alrways are collapsed and you need Lo geL C2
lnLo Lhem and surfacLanL. So, glve C2 and aL Lhe end of explraLlon, pump ln
pressure, whlch keeps alrways open on explraLlon, so you can keep C2 ln Lhem.

Lxample: plc wlLh Lype ll pneumocyLe (wlLh lamellar bodles look llke onlon, and
hyperplasLlc arLerlolosclerosls b/c Lhey are concenLrlcally shaped). 1hese lamellar
bodles conLaln surfacLanL. 1hls would lu lL as a Lype ll pneumocyLe. 1hey commonly
glve LMs of Lhe lung wlLh an alveolar macrop M
cyLoplasm. 1he Lype ll pneumocyLe ls Lhe repalr cell of Lhe lung and synLheslzes
surfacLanL.
177


8. Adu|t kesp|ratory D|stress Syndrome (AkDS)
ln Lerms of A8uS, essenLlally lL ls Lhe same as 8uS ln paLhophys, buL ls nLu18CPlL
l 8uS
Loo much lnsulln and [usL have collapsed alveoll. 8u1 ln A8uS lLs b/c you have Loo much
lnflammaLlon, Lhere ls no lnflammaLlon ln 8uS.

MCC AkDS = sept|c shock (MCC sept|c shock = L co|| from seps|s from an |ndwe|||ng
catheter, MCC DIC = sept|c shock). Lxample: ln Lhe lCu lf a pL come ln wlLh dyspnea
and lLs wlLhln 24 hrs of havlng sepLlc shock, pL has A8uS. lf pL ls ln sepLlc shock and
wlLhln 48 hrs of admlsslon and ls bleedlng from every orlflce, he has ulC. So, f|rst day =
sept|c shock, second day = AkDS, th|rd day = DIC.

athogenes|s: neuLrophlls geL lnLo Lhe lung ln sepLlc shock and sLarL desLroylng all Lhe
cells of Lhe lung (Lype l and ll pneumocyLes). So surfacLanL producLlon decreases and
resulL ls masslve aLelecLasls (collapse). Powever, Lhls ls neuLrophll relaLed (Lhe
neuLrophlls are desLroylng Lhe Lype ll pneumocyLe. 1he reason why Lhey geL hyallne
membranes ln Lhe A8uS ls b/c Lhe neuLrophlls have Lo geL ln Lhe lungs by golng Lhrough
Lhe pulmonary caplllarles, so Lhey puL holes ln Lhem as Lhey geL ouL of Lhe bloodsLream
and lnLo Lhe lungs (Lhls ls why lL ls called leaky caplllary syndrome). All Lhe proLeln and
flbrlnogen geL ln and produce hyallne membranes. 1herefore, you can acLually see
hyallne membranes ln A8uS. So, Lhere ls masslve collapse and Lhe paLhophys ls
lnLrapulmonary shunLlng. 1hls ls Lhe same ln 8uS, buL A8uS ls neuLrophll relaLed, whlch
ls a bad prognosls.

IV. neumothorax
SponLaneous pneumoLhorax and Lenslon pneumoLhorax

A. Spontaneous pneumothorax
MCC spontaneous = ruptured subp|eura| b|eb have pleura and rlghL underneaLh ls a
bleb (alr pockeL). 1he bleb (alr pockeL) rupLures causlng a hole ln Lhe pleura, so LhaL
8
whlch keeps Lhe lungs expanded. So, lf you puL a hole ln Lhe pleura, Lhen Lhe
aLmospherlc pressure ls noL negaLlve, buL ls Lhe same as Lhe alr you are breaLhlng. So,
Lhere ls noLhlng Lo hold lL open and Lherefore lL collapses. When parLs of Lhe lung
collapse, Lhere are Lhlngs LhaL wlll Lake up Lhe slack. Cne of Lhose ls Lhe dlaphragm. lf
you collapse parL of Lhe lung, Lhe dlaphragm wlll go up on LhaL slde Lo Lake up Lhe open
space on LhaL has been lefL. noL only LhaL, lf Lhere ls a collapse on one slde, Lhe Lrachea
wlll go Lo Lhe slde LhaL Lhere ls space. So, wlll have trachea| dev|at|on to the s|de of the
co||apse, and the d|aphragm |s up, |ead|ng to spontaneous pneumothorax. usually
178

seen ln Lall male Lhey have blebs LhaL rupLure and lead Lo sponLaneous pneumoLhorax.
Can also geL ln scuba dlvers b/c Lhey come up Loo qulckly, whlch leads Lo rupLure of Lhe
blebs.

8. 1ens|on pneumothorax
ulff from sponLaneou MC 1
Lear of pleura (flap), sp when you breaLhe ln Lhe flap goes up and on explraLlon lL closes.
So, Lhe alr sLays ln Lhe pleural cavlLy. So, every Llme you breaLhe, Lhe flap goes up, alr
sLays ln, and on explraLlon lL closes. So, for every breaLh you Lake, lL keeps lncreaslng
1 1he |ncrease |n pressure
starts push|ng the |ung and the med|ast|num to the oppos|te s|de. When lL pushes lL, lL
compresses Lhe lung and lL leads Lo compresslon aLelecLasls (lL ls noL deflaLed b/c of a
hole
explraLlon, and LhaL pos pleural pressure ls pushlng everyLhlng over Lo Lhe opposlLe
slde). 1hls compresslon wlll push on Lhe SvC, rlghL venL, and lefL aLrlum on Lhe opposlLe
slde. 1hls wlll compromlse blood reLurn and breaLhlng, leadlng Lo a medlcal emergency.
S Alr ls fllllng pleural cavlLy and
cannoL geL ouL. lL keeps bulldlng up and sLarLs pushlng everyLhlng Lo Lhe opp slde. WlLh
a pos lnLraLhoraclc pressure, Lhe dlaphragm wlll go down (goes up ln sponLaneous
pneumoLhorax).

V. u|monary Infect|on

A. neumon|a

1. 2 k|nds 1yp|ca| and Atyp|ca|
1yp|ca| wake feellng normal, Lhen suddenly develop a fever, producLlve cough
Atyp|ca| slow, lnsldlous onseL (feel bad over few days)

2. Commun|ty vs. Nosocom|a| (hosp|ta| acqu|red)
lf you geL pneumonla ln Lhe commun|ty Lyplcal, lL ls SLrep pneumonlae. lf
you geL pneumonla ln Lhe communlLy and lL ls
pneumonlae.
Crganlsms ln Lhe hosplLal (nosocom|a|) = L coll, seudomonas, SLaph aureus (wlll noL
geL sLrep pneumonlae ln Lhe hosplLal).

3. roduct|ve cough |n 1yp|ca| pneumon|a
keason for product|ve cough |n typ|ca| pneumon|a: have exudate (pus) and s|gns of
conso||dat|on |n the |ung Sllde: yellow areas wlLh mlcroabcesses whlch are
consolldaLlon ln Lhe lung. le lobar pneumonla = see consolldaLlon ln lung, wlLhln
179

alveoll, causlng consolldaLlon. 1herefore, wlLh Lyplcal, see consolldaLlon and pus ln
Lhe lung.
1vl (when Lhe person Lalks, feel vlbraLlons ln chesL lf have consolldaLlon ln le Lhe
upper lefL lobe, wlll have lncreased 1vl b/c lL ls a consolldaLlon, compared Lo Lhe
oLher slde so, |ncreased 1VI |nd|cates conso||dat|on L A
(egophony) slgn (pL says L and you hear A), whlspered pecLorlloquy
l 1 decreased
percuss|on, |ncreased 1VI, egophony, and pector||oquy = conso||dat|on.

WhaL lf Lhere ls a pleural effuslon overlylng Lhe lung? Cnly Lhlng you would have ls
decreased percusslon (Lhls separaLes pleural effuslon from pneumonla).
4. Atyp|ca| pneumon|as

1hey do not have a h|gh temp and do not have product|ve cough b]c they are
|nterst|t|a| pneumon|as. 1hey have lnflammaLlon of Lhe lnLersLlLlum Lhere ls no
exudaLe ln Lhe alveoll whlch ls why you are noL coughlng up a loL, and Lherefore do
S 1vl L A
aLyplcal. ALyplcal pneumonla has an lnsldlous onseL, relaLlvely nonproducLlve cough,
no slgns of consolldaLlon.

MCC typ|ca| pneumon|a = strep pneumon|ae (know the p|c) v,g6->
(aka d|p|ococcus) kx = CN G

MCC atyp|ca| pneumon|a = mycop|asma pneumon|ae, 2
nd
MCC = Ch|amyd|a
pneumon|ae, whlch are all lnLersLlLlal pneumonlas.

8ronchopneumonla: MC due Lo sLrep pneumonla, and communlLy acqulred. Lobar
pneumonla. Sllde: lobar consolldaLlon on chesL x-ray sLrep. neumonla.

a) V|ra| pneumon|as

1) kh|nov|rus = MCC common cold, Lhey are acld lablle mea
lead Lo gasLroenLerlLls ln Lhe sLomach b/c ls desLroyed by Lhe acld ln Lhe
sLomach. never wlll have a vacclne b/c 100 seroLype.

2) kSV MCC bronchlollLls whenever you lnflame small alrways, lLs leads Lo
wheezlng. 1hls ls a sma|| a|rway dz and bronch|o||t|s |s MC due to kSV and
pneumon|a. So, pneumon|a and bronch|o||t|s |s MC due to kSV |n ch||dren.

180

3) Inf|uenza drlfL and shlfL have hemaggluLlnlns, whlch help aLLach Lhe vlrus Lo
Lhe mucosa. Pave neuramlnldase bore a hole Lhrough Lhe mucosa. Ant|gen|c
-k2-qv#S ln elLher hemaggluLlnlns or neuramlnldase, do noL
need a new vacclne, &u8&u 0uoq \* 0&89\?& ln elLher
hemaggluLlnlns or neuramlnldase need a vacclne. 1he vacc|ne |s aga|nst A Ag.

b) 8acter|a| pneumon|as

1) Ch|amyd|a ps|ttacos|s from blrds (le parroLs, Lurkeys).
2) Ch|amyd|a trachomat|s a llLLle kld was born and a week laLer he was
wheezlng (blg Llme), pneumonla, lncreased A dlameLer, Lympanlc percusslon
sounds, no fever, eyes are crusLy (boLh sldes), welrd cough staccato cough
qvqIUv-kq-S-k-Iu----
2
nd
week = Ch|amyd|a trachomat|s). (MC overa|| of con[unct|v|t|s |s
|nf|ammat|on of erythromyc|n drops).
c) nosp|ta|-acqu|red gram-negat|ve pneumon|as

1) seudomonas waLer lovlng bacLerla, Lherefore see ln pL ln lCu when on a
8LSl8A1C8. pL waLer unlL wlLh green producLlve cough wlLh.

2) k|ebs|e||a famous ln Lhe alcohollc, however, alcohollc can also geL sLrep
pneumonla. So, how wlll you know sLrep vs. klebslella? Alcohollc wlLh hlgh
splklng fevers, producLlve cough of MuCClu appearlng spuLum Lhe capsule
of klebslella ls very Lhlck. Llves ln Lhe upper lobes and can cavlLaLe, Lherefore
can confuse wlLh 18.

3) Leg|one||a aLyplcal cough, nonproducLlve cough, very slck can klll you, from
waLer coolers (waLer lovlng bacLerla), seen ln mlsLs ln grocerles or aL
resLauranLs. Lxample: classlc aLyplcal pneumonla, Lhen pL had hyponaLremla
Lhls ls Leglonella. Leglonella [u
organs such as llver dz, |nterst|a| nephr|t|s and knocks off Lhe [uxLaglomerlur
cells, and kllls Lhe renln levels, low aldosLerone and Lherefore lose salL ln Lhe
urlne, |eads to hyponatrem|a (low renln levels wlLh low aldosLerone). 8x =
eryLhromycln

8. Iunga| Infect|ons
1he two system|c fungus are Cand|da and n|sto

1. Cand|da seen ln lndwelllng caLheLers (usually Lhose ln Lhe subclavlan). And geL
Candlda sepsls
181


2. n|stop|asmos|s = M|dwest (Chlo/1ennessee valley) carrled by dung of sLarllngs and
baLs ofLen seen ln cave explorers, or spelunkers. 1hey develop non-producLlve
cough. PlsLo ls Lhe only sysLemlc fungus LhaL has yeasLs phagocyLosed by alveolar
macrophages.

3. Cryptococcus = |geons looks llke mlckey mouse yeasL forms are narrow based
buds. Lxample: n? exec wlLh plgeons roosLlng ln alr condlLloner and developed non
producLlve cough. Lxample: palnLer developed resp lnfecLlon worked on 8rooklyn
brldge wlLh plgeons, how do you LreaL? Amphoter|c|n 8.

4. 8|astomycos|s = SL uSA = skln and lung lnfecLlons, broad based bud

S. Cocc|d|o|domycos|s: SW uSA (new Mexlco, Arlzona, souLhern Cal. = coccldlomycose
has spherule endospores (know Lhe plc). Lxample: ln LA earLhquake, a # of people
had nonproducLlve coughLhe arLhrospore (Lhe lnfecLlous form) ls ln dusL. WlLh Lhe
earLhquake, dusL comes up, breaLhe lL ln. Lxample: man LhaL ls an lndlan arLlfacL
explorer ln Lhe sonaran deserL, whlch ls ln Arlzona, and ls a CAvL explorer LhaL
developed nonproducLlve cough Lhls ls CCCCICMCCSIS (noL PlsLo b/c noL Lhe
MldwesL).
6. Asperg|||us
1) loves Lo lnhablL abandoned 18 fungus cavlLles fungus ba|| (aspergllloma, a very
common cause of masslve hemopLysls). Lxample: lefL upper lobe cavlLary leslon
and asp love Lo llve ln Lhere = fungus ball
2) vessel lnvader, Lherefore wlll lnvade Lhe vessels ln lung, leadlng Lo thrombos|s and
|nfarct|on
3) allergles Lhe mold, leadlng Lo exLrlnslc asthma and Lype l P?

So, Lhree manlfesLaLlons: fungus ball, lnvaslve vascular dz produclng hemorrhaglc
lnfarcLlons of Lhe lung, and asLhma. Lxample: plc of corona componenL of
Asperglllus (looks llke a crown) sepLaLe ls very characLerlsLlc (mucormycosls ls
nonsepLaLe and has wlde angles, whlle Asperglllus has narrow angles ln lLs buddlng


7. C (neumocyst|t|s car|n|| pneumon|a
lungus (used Lo be a proLozoa) b/c more Lhlngs ln Lhe cell wall LhaL look llke a
l Plv MC Alu ng leslon (as soon as Lhe helper 1 cell
cL ls 200, lL usually shows up). used Lo be MCC deaLh ln Alus pL, buL now has gone
down, b/c as soon as your Cu4 cL ls 200, dr. wlll puL pL on prophylacLlc Lherapy wlLh
1M-SMx.
182


When Laklng 1M-SMk and protect|ng aga|nst C, would oLher organlsm ls Lhe pL
proLecLed from? 1oxop|asmos|s. (so, you geL 2 for 1). MCC space occupylng leslon
wlLhln Lhe braln ln a pL wlLh Alus= 1oxoplasmosls

Seen w|th s||ver sta|n: cysLs of C can be seen look llke plng pong balls, seen ln
alveoll, leadlng Lo alveolar lnfllLraLe, leadlng Lo dyspnea, Lachypnea, foamy bubbly
lnfllLraLe, on chesL x-ray, looks all whlLe ouL b/c of Lhe lnvolvemenL of Lhe lung
however, noL only seen ln lungs, can be seen ln any parL of Lhe body also seen ln
Plv

CLher organlsms LhaL are only seen wlLh sllver sLaln: barLenella henselae (baclllary
anglomaLosls), Leglonella (noL vlsuallzed wlLh gram sLaln, Lherefore use buLuly???
sllver sLaln)

8. 18
Crganlsm ln upper lobe of lungs (play odds) 18 see cavlLary leslon, whlch ls
reacLlvaLlon 18 (noL prlmary). rlmary 18 ls Lhe lower parL of Lhe upper lobe or Lhe
upper parL of Lhe lower lobe and close Lo Lhe pleura (klnd of ln Lhe mlddle of Lhe
lobe). rlmary 18 has a Chon focus and a Chon complex. MosL people recover,
when pL ls lmmunocompromlsed, lL leads Lo reacLlvaLlon and goes lnLo Lhe apex and
produces a cavlLary leslon. 1here |s no Ghon focus or comp|ex |n react|vat|on 18,
on|y pr|mary 18.

Cther th|ngs that cav|tate |n upper |obes:
W 18 P
Whlch cancer can cavlLaLe ln Lhe lung? Squamous Cell carclnoma of Lhe lung
Whlch bacLerla (LhaL has a blg mucous wall around lL) can also produce cavlLaLlons ln
Lhe upper lobe? klebslella pneumonlae.
WhaL ls acld fasL sLaln sLalnlng? Mycollc aclds.
So, [usL b/c someLhlng ls cavlLaLlng Lhe upper lobe, lL ls noL necessarlly 18.

C. Iore|gn 8od|es
lf you are stand|ng or s|tt|ng up, forelgn bodles wlll go Lo posterobasa| segment of the
r|ght |ower |obe. 1hls ls Lhe mosL posLerlor segmenL of Lhe rlghL lower lobe.

lf you are lylng down (MC way Lo asplraLe Lhlngs), forelgn body wlll go Lo superlor
segmenL of Lhe rlghL lower lobe.
lf you are lylng on Lhe rlghL slde, can go Lo 2 places 1) mlddle lobe 2) posLerlor
segmenL of rlghL upper lobe (Lhls ls Lhe CnL? one LhaL ls ln Lhe upper lobe.
183

lf you are lylng down on your lefL, and asplraLe, lL wlll go Lo Lhe llngula.

Summary:
S|tt|ng]stand|ng = posterobasa| segment of r|ght |ower |obe
8ack: super|or segment of r|ght |ower |obe
k|ght: m|dd|e or sup segment of r|ght |ower |obe
Left: ||ngu|a

D. Abscess
MCC abscess = asp|rat|on of oropharyngea| mater|a|
Seen commonly ln sLreeL people LhaL do noL have good denLlLlon, may be drunk and fall
and oropharyngeal maLerlal wlll be asplraLed. AsplraLe conslsLs of aerobes and
anaerobes, leadlng Lo puLrld/sLanch smell. 1he asplraLe ls a mlxLure of all Lhese
organlsms: Mlxed aerobes and anaerobes, fusobacLerlum, bacLeroldes. Can geL
absecces ln Lhe lung from pneumonla: sLaph aureus, klebslella (however, MCC ls
asplraLlon), see fluld cavlLles ln lung on x-ray.

VI. u|monary Vascu|ar D|sease:
A. u|monary Lmbo|us
2 Lypes of emboll Llny ones LhaL produce wedge shaped hemorrhaglc emboll or can
chlp off large ones. Where do mosL ul emboll embollze from? MC Sl1L for Lhrombosls
ls Lhe deep velns of Lhe lower leg. 1hls ls nC1 Lhe mosL common slLe for embollzaLlon, lL
ls Lhe femoral veln (Lhls ls Lhe MC slLe for embollzaLlon). Makes sense b/c venous cloLs
propagaLe Loward Lhe hearL (deep velns Lo Lhe femoral veln, and Lhe femoral veln ls a
larger vessel, Lherefore lL ls more llkely Lo chlp off). So, Lhe femoral veln ls Lhe MC slLe
for embollzaLlon Lo Lhe lung. 1he deep velns are Lhe MC slLe where deep venous
Lhrombosls beglns. (when lL geL Lo Lhe femoral veln, lL ls dangerous for embollzaLlon).
So, small ones produces hemorrhaglc lnfarcL LhaL ls only lf you have an underlylng lung
l l have abnormal lungs.
Powever, lf you have preexlsLlng lung dz you wlll lnfarcL. 83 of Lhe Llme embolus wlll
noL produce lnfarcL. Powever, ln Lhe 13, mosL of Lhe pLs wlLh lnfarcLs have preexlsLlng
lung dz (le Lhey are smokers). 1he oLher Lype of embolus ls a saddle embolus (lL ls huge)
and blocks off Lhe orlflces of Lhe pulmonary vessels and pulmonary arLerles. lf you
knock off aL leasL 3 ouL of Lhe 3 orlflces, you are dead ln a mllllsecond, so Lhere ls no
lL produces acuLe rlghL hearL sLraln and
lmmedlaLe deaLh. Screen|ng test of cho|ce: Vent||at|on perfus|on scan w||| have
vent||at|on, no perfus|on, conf|rmatory test |s pu|monary ang|ogram.

VII. kestr|ct|ve u|monary D|sease

184

kestr|ct|ve someLhlng ls resLrlcLlng lL from fllllng. Lxample: resLrlcLed fllllng of Lhe hearL =
resLrlcLlve cardlomyopaLhy. Cr resLrlcLlon ln fllllng up of Lhe lungs wlLh alr. Pave 2 Lerms:
comp||ance (f||||ng term, |nsp|rat|on term) and e|ast|c|ty (reco||, exp|rat|on term),

lor resLrlcLlve lung dz, plcLure a hoL rubber boLLle for resLrlcLlve lung dz. 1he hoL rubber
comp||ance |s decreased and lL ls hard Lo flll Lhe
S lbrosls (lnLersLlal flbrosls,
MC l
happens Lo Lhe elasLlclLy? lncreases. So, compllance ls decreased and cannoL flll lL up, buL
once you do flll Lhe lung up, lL comes ouL qulckly (e|ast|c|ty |ncreases).

Lxample: pL wlLh sarcold dlff Lo flll lungs, buL geL lL ouL fasL (due Lo flbrosls). So, all 1LC,
8v, 1v (all lung capaclLles have all equally decreased). lLv1/lvC on splromeLer Lake a
deep breaLh (le pL wlLh sarcold) lLv1 (amounL you geL ouL ln one sec normally lL ls 4
llLers) ls decreased, lvC (LoLal LhaL goL ouL afLer deep lnsplraLlon) ls decreased (b/c
lncreased elasLlclLy) Lhls ls Lhe same as lLv1, so Lhe raLlo ls ofLen 1. normally, Lhe lvC ls
3 llLers, and Lhe lLv1 ls normally 4 llLers so, Lhe normal lLv1/lvC raLlo ls 4/3 =80. 8/c
Lhe elasLlclLy ls lncreased, Lhe lvC ls Lhe same as lLv1, and Lherefore Lhe rat|o |s |ncreased
Lo 1 lnsLead of 0.8.

\>ouu>&8?4
1. neumocon|os|s a famous ln blg clLles (LA, n?). Cole
worker pneumoconlosls esp. ln wesL vlrglnla/enn, have an anLhrocoLlc plgmenL
LhaL causes a flbrous rxn ln Lhe lung, leadlng Lo resLrlcLlve lung dz. Pave an lncreased
lncldence of 18, buL noL cancer.

2. S|||cos|s SandblasLers geL grafflLl off Lhlngs, or work ln foundrles and deal wlLh rocks
(le quarLz), and break Lhem down, and breaLhe ln dusL, leadlng Lo slllcoses). Pave
nodules ln Lhe lung LhaL are hard has rock (llLerally) b/c Lhere ls quarLz ln Lhem and lL
looks llke meLasLaLlc dz ln Lhe lung (slllca dloxlde whlch ls sand ln Lhe lung) agaln,
lncreased of 18, noL cancer. lf pL happens Lo have rheumaLold arLhrlLls, and also has
one of Lhese pneumoconlosls (le Cole workers), have a poLenLlal for a syndrome,
whlch ls called caplan syndrome. Cap|an syndrome conslsLs of rheumaLold nodules
ln Lhe lung (same as exLensor surfaces ln Lhe arm). 8heumaLold arLhrlLls commonly
lnvolves Lhe lung wlLh flbrosls. And rheumaLold nodules can form ln Lhe lung. 1he
combo of rheumato|d arthr|t|s (rheumato|d nodu|es) |n the |ung, p|us
pneumocon|os|s (s|||cos|s]asbestos|s]Co|e workers) = cap|an syndrome.

3. Asbestos asbesLos flbers look llke dumbbells (Lherefore ez Lo recognlze). 1hese are
called ferruglnous bodles. AsbesLos flbers coaLed wlLh lron, Lherefore can call Lhem
185

elLher asbesLos bodles or ferruglnous bodles. MC pulmonary leslon assoc wlLh
asbesLos ls noL cancer lL ls a flbrous plaque wlLh a pleura, whlch ls b9 (noL a
precursor for mesoLhelloma). MC cancer assoc w|th asbestos = pr|mary |ung cancer,
2
nd
MCC = mesothe||oma, wh|ch |s a ma||gnancy of the serosa| ||n|ng of the |ungs. lf
you are a smoker and have asbesLos exposure, you have an lncreased chance of
geLLlng prlmary lung cancer. 1hls ls a good example of synerglsm (oLher causes of
lung cancer (SCC) lnclude smoklng, alcohol). AsbesLos + smoker = wlll geL cancer.
1here ls no lncreased lncldence of mesoLhelloma wlLh smoklng (noL synerglsLlc).
Lxample: 8oofer for 23 years, nonsmoker (do Lell you, buL you had Lo know LhaL 23
years ago, all Lhe rooflng maLerlal had asbesLos ln lL, ln oLher parLs of n?, many
bulldlngs were Lorn down, and Lhere was asbesLos ln Lhe rooflng of Lhose bulldlngs,
whlch was lnhaled by many people, and 10-30 years laLer Lhey developed prlmary
lung cancer or anoLher compllcaLlon of asbesLosls). WhaL would he mosL llkely geL?
rlmary lung cancer (prlmary pleural plaque was noL Lhere). lf he was a smoker?
rlmary lung cancer. MesoLhelloma Lakes 23-30 years Lo develop. Lung cancers Lake
abouL 10 years Lo develop. Lung cancers are more common, and you dle earller.
WhaL ls Lhe maln cause of asbesLos exposure? 8oofers or people worklng ln a naval
shlpyard (b/c all Lhe plpes ln Lhe shlp are lnsulaLed wlLh asbesLos), also ln brake llnlng
of cars and headgear.

4. Sarco|dos|s =2
nd
MCC restr|ct|ve |ung dz.
Lxample: classlc x-ray lymph nodes (hllar lymph nodes are blg), hazlness seen, Loo,
whlch ls lnLersLlal flbrosls. Sarco|d |s a granu|omatous dz LhaL has nC relaLlonshlp Lo
lnfecLlon (cause = unknown). Causes a noncaseat|ng granu|oma (noL caseaLlng b/c
no relaLlonshlp Lo 18 and sysLemlc fungal lnfecLlons). 1he lungs are ALWA?S lnvolved
(lungs are Lhe prlmary LargeL organ), and more common ln blacks. Lxample: black
person, 33 y/o, wlLh dyspnea, see hllar nodes on x-ray, uvllLls (blurry vlslon Lhls ls
lnflammaLlon of Lhe uveal LracL Lhls dz always affecLs someLhlng ln Lhe face, and
Lhe face Lhe 2
nd
MC slLe a leslon wlll occur wlLh Lhls dz, can also lnvolve sallvary
glands or lacrlmal glands someLhlng ln Lhe head/neck/face area (behlnd Lhe lungs).
1hls dz ls a dx of excluslon, Lherefore musL rule ouL anyLhlng LhaL causes granuloma
(18, PlsLo), along wlLh Lhe correcL physlcal presenLaLlon = Sarcoldosls. kx = stero|ds.
ACL enzymes are very hlgh ln Lhese pLs b/c granulomas ln kldney, hyperca|cem|a
macrophages (eplLhelold cells) make 1-alpha-hydroxylase. lf Lhey are maklng 1-
alpha-hydroxylase, whaL ls Lhe mech of hypercalcemla? PypervlLamlnosls u. you are
second hydroxylaLlon more vlL u and Lherefore have excess vlL u, and vlL u promoLes
reabsorpLlon of calclum and phosphorus, leadlng Lo hypercalcemla. 1h|s |s the MC
non|nfect|ous cause of granu|omatous hepat|t|s (18 |s the MCC of |nfect|ous
hepat|t|s, 2
nd
MC = pneumocon|os|s).

186

]]]]][oP]o]oo]] )
1 u Lhey
are 8C1P seen ln farmers. So, remember one, Lhe oLher ls Lhe oLher!

S||of|||ers dz puL Lhlngs ln sllos, whlch ls a closed space, and fermenLaLlon of gas
occurs, Lhe gas ls nlLrogen dloxlde Lxample: farmer wenL lnLo a room ln hls barn
and suddenly developed wheezlng and dyspnea, why? 8/c he Look ln nlLrogen
dloxlde, whlch ls a fermenLlng problem. (sllo can explode b/c gas from
fermenLaLlon).

d\?>&8 ] thermoph|||c act|nomyces (a mo|d).
Lxample: on LracLor, dusL belng blown up ln Lhe alr and Lhermophlllc acLlnomyces
(whlch ls a mold) ls lnhaled, leadlng Lo hypersenslLlvlLy and P? pneumonlLls and
Lhey end up wlLh a resLrlcLlve lung dz.

8ys|nos|s worker ln LexLlle lndusLry, and Lhey geL dyspnea. 1hese are Lhe P? and


Goodpasture syndrome
8eglns ln Lhe lungs wlLh a resLrlcLlve lung dz (wlLh coughlng up blood
hemopLysls), and ends up very shorLly wlLh renal dz (Lherefore, lL sLarLs ln Lhe lung
and ends ln Lhe kldneys). 1hls ls a resLrlcLlve lung dz.

VIII. Cbstruct|ve |ung Dz

A. Dea|s w|th comp||ance]e|ast|c|ty concept
In obstruct|ve |ung dz, no prob gett|ng a|r |n, but have a prob|em |n gett|ng the a|r out.
W 8
so lL ls very ez Lo flll up Lhe lungs. Powever, b/c Lhe elasLlc Llssue supporL ls desLroyed, lL
ls very dlfflculL hard Lo geL lL ouL b/c lL collapses on explraLlon, so you can geL alr ln, buL
cannoL geL alr ouL. ln a pL wlLh obsLrucLlve alr dz, Lhey breaLhe ln wlLh no problem, buL
have Lrouble geLLlng lL ouL. So, someLhlng ls lefL over ln Lhe lung cannoL geL all Lhe alr
ouL, Lherefore Lhe resldual volume ls lncreased (whenever someLhlng ls lefL over, lL ls
S
whlch means LhaL Lhe 1LC wlll lncrease, whlch means LhaL Lhe dlaphragm wlll go down
b/c as Lhe lungs are over lnflaLed, and Lhe A dlameLer wlll go ouL. So, wlLh obsLrucLlve
lung dz, you have lncreased A dlameLer and dlaphragms go down (depressed). 1here ls
only a cerLaln amounL of expanslon your chesL can go. LvenLually, Lhe chesL sLarLs Lo
compress oLher volumes (as you Lrap alr and resldual volumes go up). So, Lldal volume
sLarLs decreaslng, vlLal capaclLy goes down b/c Lhe resldual vol ls lncreaslng and you are
187

compresslng oLher volumes. So, 1LC and kV |ncreases, everyth|ng e|se decreases. Cn
splromeLer, lLv1 ls very low (usually 1 normally lL ls 4). ln oLher words, you have a
beLLer lLv1 wlLh resLrlcLlve lung dz b/c you can geL alr ln. 1he lvC (LoLal amL Lhey can
geL ouL) ls 3 llLers (vs. 3 llLers). When you do a rat|o of ILV1]IVC, the rat|o has
kq--v-q-v--k-SI

C|ass|c CCD x-ray: hard Lo see Lhe hearL, wlLh depressed dlaphragms (aL level of
umblllcus), lncreased A dlameLer dx? Classlc obsLrucLlve dz x-ray prob geLLlng alr
ouL, Lherefore Lhe dlaphragm ls down and A dlameLer ls lncreased. Lxample: 3 monLh
old can have Lhls same flndlng due Lo 8Sv
Lxample: newborn wlLh Chlamydla LrachomaLls pneumonla b/c he ls Lrapplng alr.

7 x0 o u >&8 ?4 0&u &0uu/ &0uu/
emphysema, asthma. 1he ones assoclaLed wlLh smoklng are bronchlLls and emphysema.

1. Chron|c 8ronch|t|s
ure|y a c||n|ca| dx = t has product|ve cough for 3 months out of the year for 2
consecut|ve years. Where ls Lhe dz? 1ermlnal bronchloles (you have maln sLem
bronchus, segmenLal bronchl, Lermlnal bronchloles, resp bronchloles, alveolar ducLs,
alveoll). As soon as you hlL Lhe Lermlnal bronchloles, Lhese are small alrway, lL ls all
LurbulenL alr up Lo Lermlnal bronchloles. AfLer LhaL, lL ls parallel branchlng of Lhe
alrways. 1he LurbulenL alr hlLs Lhe Lermlnal bronchloles and Lhen hlLs a masslve cross
l branchlng of Lhe small
alrways. So, Lhe alrflow changes from LurbulenL Lo lamlnar alrflow. 8y Lhe Llme you
hlL Lhe resp unlL, lL ls noL movlng Lhe alr. )\>>u?u&o>\\u&
of the term|na| bronch|o|es, |eads to wheeze. 1ermlnal bronchloles are Lhe slLe of
chronlc bronchlLls. 1hls ls Lhe same area as asLhma and bronchlollLls. More prox Lo
Lhe Lermlnal bronchloles, ln bronchlLls, you wlll geL a mucus gland hyperplasla, and a
1 acLual area of obsLrucLlon ls
Lhe Lermlnal bronchlole. Pave gobleL cell meLaplasla and mucous plugs. 1hlnk abouL
havlng one Lermlnal bronchlole and one mucous plug Lhls ls affecLlng a ma[or cross
secLlonal area of lung b/c all Lhe parallel branches LhaL derlve from here wlll noL have
CC2 ln Lhem, and Lhey are Lrylng Lo geL alr pasL Lhe mucous plug, buL cannoL. So,
there |s a nUGL vent-perfus|on m|smatch. 1hls ls why Lhey are ca||ed b|ue boaters
they are cyanot|c. 1hey have mucous plugs ln Lhe Lermlnal bronchloles and cannoL
rld CC2.
2. Lmphysema

noL ln Lhe Lermlnal bronchloles. lL ls ln Lhe resp unlL (resp un|t |s where gas
exchange occurs cannoL exchange gas ln Lhe Lermlnal bronchloles aka nonresp
188

bronchlole), lL ls Lhe prlmary place for explraLory wheeze and small alrway dz,
however. Gas exchange occurs |n the resp bronch|o|e, resp a|veo|ar duct and
a|veo||. Cnly need Lo know 2 emphysemas: centro|obu|ar and panac|nar.
Lmphysema affecLs gas exchange and where lL affecLs Lhe alrway ls more dlsLal,
compared Lo chronlc bronchlLls (proxlmal). So, when you have emphysema wlLh all
Lhe lnflammaLlon assoclaLed wlLh lL, noL only desLroy Lhe resp unlL, buL also Lhe
vasculaLure assoclaLed wlLh lL. 1herefore, there |s an even |oss of vent||at|on and
perfus|on. So, w||| NC1 have retent|on of CC2 |n these pts. When you have a
problem wlLh a mucous plug ln Lhe Lermlnal bronchlole, whlch ls way more prox and
a greaL cross secLlonal area of Lhe lung ls affecLed, Lhere ls gonna be a problem Lhere,
however when you are ouL Lhls far (ln emphysema) and also desLroylng Lhe vessels,
you w||| not have an |ncrease |n CC2. 1hls ls why Lhey are called p|nk puffers, and
Lhls ls why many of Lhem have resp alkalosls.

a) Centro|obu|ar most assoc|ated w|th smok|ng and |nvo|ved w|th the upper
|obes. So, lL ls an upper lobe emphysema, and Lhe prlmary porLlon of Lhe resp
unlL LhaL ls desLroyed ls Lhe resp bronchlole (Lhls ls Lhe very flrsL Lhlng LhaL smoke
hlLs). neuLrophlls wlll damage lL b/c all people LhaL smoke have more neuLrophlls
ln Lhelr lungs, and smoke ls chemoLacLlc for neuLrophlls. ALL smokers have
lncreased neuLrophlls ln Lhelr lungs. WhaL does alpha- l
anLlelasLase (lLs only purpose ls Lo desLroy elasLases produced by neuLrophlls
LhaL ls lLs funcLlon. lf you are a smoker, LhaL ls denaLured. So, you also have an
acqulred alpha- u -1 anLlLrypsln, and
have Loo many neuLrophlls ln Lhe lungs. 1hls ls a Lerrlble combo. 1hls why
neuLrophlls have no problem ln desLroylng Lhe elasLlc Llssue supporL of Lhe
resplraLory bronchloles. So, you breaLh alr ln, whlch ls no problem, buL you Lry Lo
geL lL ouL, and Lhere ls no elasLlc Llssue supporL and leads Lo lung expanslon Lhls
ls why blebs are found Lhere are blg cysLlc spaces ln Lhe lung lL has Lrapped alr
ln Lhere b/c Lhere ls no elasLlc Llssue, so when lL Lrles Lo geL by, lL [usL expands.
1hls ls centro|obu|ar emphysema of the ULk |obes.

b) anac|nar Lmphysema yLhlng le ln pancyLopenla,
ALL Lhe cells decreased). So, panaclnar means LhaL Lhe Ln1l8L resp unlL ls decreased
b/c lL ls assoclaLed wlLh NC a|pha 1 ant|tryps|n. 1hls ls a geneLlc dz auLo rec ] the
LIVLk does not make |t. So, aL a young age, you develop desLrucLlon of enLlre resp
unlL of Lhe LCWL8 lobes, so th|s |s a LCWLk |obe emphysema. So, you can see LhaL
Lhe resp bronchloles are knocked ouL, Lhe alveolar ducLs are knocked ouL, alveoll
knocked ouL. So, you breaLhe ln, and Lhls enLlre resp unlL caLches lL Lhls ls ln Lhe
lower lobes.

189

Smokers, whlch have an acqulred alpha-1 anLlLrypsln def, can geL an elemenL of
panaclnar emphysema ln Lhe lower lobes, Loo. So, smokers can geL 2
ocks off Lhe
resp bronchlole) and ln Lhe lower lobes, geL a panaclnar Lype of paLLern.
1herefore, can geL upper Anu lower lobe emphysema, and 2 dlff Lypes of
emphysema.

3. 8ronch|ectas|s
Pave bronchlecLasls see bronchl golng ouL Lo Lhe pleura (abnormal). When you see
bronchl golng ouL furLher Lhan Lhe hllum, Lhls ls bronchlecLasls.
Mech: |nfect|on, destruct|on of the e|ast|c t|ssue support, d||atat|on of the a|rways.
SegmenLal bronchl, flll wlLh pus. Lxample
(noL [usL a Lablespoon) of pus, b/c Lhey are Lrapped.

a) Causes:
1) MCC bronchlecLasls ln uSA = cyst|c f|bros|s. lf parenL wlLh chlld has cysLlc
flbrosls, wlll see huge pus comlng ouL of bronchl, a couple Llmes per day.
2) MCC bronchlecLasls ln 3
rd
world counLrles = 18.

3) g8&? &\ (aka lmmoLlle cllla syndrome). 9+2 conflguraLlon
arrangemenL wlLh cllla and mlcroLubules. 1he problem wlLh lmmoLlle cllla
syndrome ls an absenL dyneln arm. 1he 9 mlcroLubules on Lhe ouLslde have arms
LhaL keep Lhem LogeLher Lhese dyneln arms are mlsslng. So, when Lhese arms
are mlsslng, Lhe cllla cannoL move. So, Lhe places wlLh cllla noL movlng are
affecLed: Lhese places are slnuses (why s|nus|t|s ls a problem), bronch|ectas|s (b/c
Lhere ls cllla psuedosLraLlfled columnar eplLhellum ls affecLed), males and
females are |nfert||e (b/c Lhe Lall on Lhe sperm cannoL move Lhe Lall ls a
modlfled cllla Lhey head ls movlng, buL Lhe Lall ls weak. Women are lnferLlle,
Loo, b/c Lhe falloplan Lube needs cllla Lo carry Lhe egg down. Crgans are |ocated
on the oppos|te s|de (dextrocard|a, w|thCU1 transpos|t|on of great vesse|s).

4. Asthma
Can be exLrlnslc (Lype 1 P?) and lnLrlnslc: lnvolves chemlcals people ln Lhe
workplace can geL Lrlad asLhma, whlch lnvolves people Laklng nSAlus Many people,
le aLhleLes wlll geL exerLlonal asLhma and wheeze cromolyn na ls Lhe uCC for Lhese
paLlenLs. Cold Lemps can cause asLhma. 1ype l P? has noLhlng Lo do wlLh Lhese
causes of asLhma. 1he wheezlng ls due Lo lnflammaLlon of Lhe Lermlnal bronchloles
L1 C u L C
and narrowlng of Lhe alrways.
Ik. Lung Cancer
190


A. er|phera||y |ocated vs. centra||y |ocated
1. Centra||y |ocated (ma|nstem bronchus):
Pave Lhe hlghesL assoclaLlon wlLh smoklng. lnclude squamous cell carclnoma and
small cell carclnoma. 1hese are generally cenLrally locaLed, hence malnsLem
bronchus Lypes of locaLlons. Squamous cell are more common Lhan small cell
carclnomas.

2. er|phera||y |ocated:
Adenocarc|nomas (Lhe more common prlmary lung cancer, more common Lhan
squamous) are more perlpheral Lhan cenLral. ShlfLed Lo Lhe perlphery b/c of Lhe
fllLers of Lhe clgareLLes. 1he fllLers prevenLed Lhe large carclnogens from passlng ln,
buL Lhe small carclnogens sLlll passed Lhrough, and Lhey are noL Lrapped ln Lhe maln
sLem, buL Lrapped ln Lhe perlphery.

1here are aL leasL 3 or 4 Lypes of adenocarclnoma. Cne obvlously does have a
smoklng relaLlonshlp, whlle Lhe oLhers do noL. 1he ones LhaL do noL have a smoklng
relaLlonshlp lnclude bronchlolar alveolar carclnoma, and large cell adenocarclnoma
of Lhe lung (scar cancers).

8. Cyto|ogy: know whaL squamous cancer looks llke wlLh a pap smear. A loL of people
Lhlnk LhaL Lhe apanlcolaou sLaln ls only done for cervlcal carclnoma. 1hls ls noL Lhe case.
1h|s |s a famous sta|n (pap smear) used for a|| cyto|og|ca| spec|mens on for a|| organs. 1he
- -S #- -vqI Sllde: (plc) pL LhaL ls a smoker wlLh a cenLrally locaLed
mass. Showlng spuLum sample wlLh a apanlcolaou (pap smear) sLaln has red keraLln,
whlch ls squamous cell carclnoma. lf Lhls were a cervlcal pap smear from a woman LhaL ls
40 years of age, Lhls ls squamous cell carclnoma. 1he keraLln ls sLalnlng brlghL red! (brlghL
red cyLoplasm = keraLln = squamous cell carclnoma). apanlcolaou sLalns keraLln brlghL red.

Lxample: small cells LhaL look llke lymphocyLes Lhls ls sma|| ce|| carc|noma. 1hls ls more
dlfflculL Lo dx, b/c someLlmes dlff Lo Lell Lhe dlfference from lymphocyLes. Sllde shows
mallgnanL cells. Small cell carclnoma ls Lhe mosL mallgnanL cancer of Lhe lung. 8x?
8adlaLlon and chemo (noL surgery). 1hese are auput tumors w|th neurosecretory granu|es
and S-100 Ag pos|t|ve. 1hey can make AuP and AC1P.

A sllghLly less mallgnanL Lumor wlLh aupuL orlgln ls Lhe bronch|ocarc|no|d. lL ls a low grade
mallgnancy of Lhe same Lypes of cells LhaL produce small cell carclnoma. So, Lhey can
lnvade, meL, and produce carclnold syndrome lf Lhey make lncreased amounL of seroLonln.
1 lL [usL goes sLralghL lnLo Lhe
bloodsLream. lL ls very uncommon.
191



C. Cancer:
MC cancer of lung = meLs le see many meLasLaLlc nodules all over lung, lf you play
odds, whaL ls Lhe prlmary cancer? breasL (whlch Lhe MC meL Lo Lhe lung, or ln oLher
words, lL ls Lhe MC cancer of Lhe lung).

Summary of |ung cancer |n the |ung:
MC cancer = mets
MC pr|mary cancer = pr|mary adenocarc|noma of the |ung, fo||owed by squamous and
sma|| ce|| carc|noma.
Worst cancer (worst prognos|s): sma|| ce|| carc|noma.

1&?&\ pancoasL Lumor/superlor sulcus Lumor Lumors LhaL are ln Lhe upper
lobe posLerlorly (ln posL medlasLlnum), mosL of Lhe Llme ls caused by squamous carclnoma ln
W 1
Lrunk of Lhe brachlal plexus, so can geL lower Lrunk brachlal plexus llke flndlngs, and can also
affecL Lhe superlor cervlcal gangllon. 1hls ls ln Lhe posLerlor medlasLlnum, Lherefore wlll end
P knock|ng CII sympathet|c act|v|ty ptos|s
(lld ls lower), anhydrous (lack of sweaLlng), m|os|s (ln sympaLheLlc, whlch ls flghL or fllghL,
normally have mydrlasls, whlch dllaLes Lhe pupll wlLh flghL or fllghL, wanL as much llghL as
posslble, Lherefore dllaLlng pupll, buL Lhls ls cuL off, leadlng Lo mlosls). uo noL confuse wlLh
SvC syndrome, Lhls ls [usL blocklng off SvC.

MyasLhenla has Lo do wlLh Lhymoma, whlch ls locaLed ln Lhe anLerlor medlasLlnum.

LxudaLe vs. LransudaLe (< 3 grams, wlLhouL many cells ln lL)
MCC pleural effuslon due Lo LransudaLe = Pl

L
192

CnA1Lk 9: GI

I. D|seases of the Mouth

A. nerpes s|mp|ex, Perpes lablalls-(fever bllsLers and cold sores), prlmary herpes ls a
sysLemlc lnfecLlon. Pave fever, vlremla, generallzed lymphadenopaLhy, and goes away,
lL sLays ln Lhe sensory ganglla (dormanL ln Lhe sensory ganglla) every now and Lhen lL
can come ouL wlLh sLress, menses, whaLever, and wlll form veslcles. 8ecurrenL herpes ls
no longer sysLemlc Lhere ls no more fever, and no more lymphadenopaLhy. CLher
vlrus LhaL remaln laLenL herpes zosLer remalns laLenL ln Lhe sensory ganglla, can
lnvolve Lhe skln, llps, dermaLomes. So, pr|mary herpes |s system|c, recurrent herpes |s
not. (No fever = no |ymphadenopathy).lf we enrooL and sLaln, wlll see lncluslon ln
herpes lL ls a mulLlnucleaLed cell wlLh lnLernuclear lncluslons. 8lopsy of a
mulLlnucleaLed cell from a pL wlLh Plv, wlLh mulLlple lnLernuclear lncluslons herpes
esophaglLls.

8. na|ry Leukop|ak|a
1hls ls noL an Alus deflnlng leslon, buL lS a preAlus Lype of lnfecLlon as ls Lhrush,
shlngles. LocaLed on Lhe laLeral boarder of Lhe Longue. Pas noLhlng Lo do wlLh dysplasla
(leukoplakla). lL ls a resulL of an |nfect|on from L8V. So, do noL geL Lhe ldea LhaL lL ls a
preneoplasLlc leslon. SLarL seelng Lhls before Lhe helper 1 cell counL geL Lo 200. 8x -
Acyclovlr

C. 1hrush (ora| cand|d|as|s)
ln an adulL, Lherefore can assume LhaL lL ls ln an lmmunocompromlsed paLlenL, where
Lhere ls a defecL ln cellular lmmunlLy. ln klds (newborns), Lhey can geL lL from Lhe mom
on Lhe way ouL. Powever, lL ls noL a slgn of lmmunocompromlse.
S lC

D. Lxudat|ve tons||||t|s
30 chance that |t |s group A beta hemo|yt|c strep. 70 chance that |t |s a v|rus,
adenov|rus, L8V. So, when you see exudaLlve LonsllllLls, cannoL assume lL ls bacLerla
and lmmedlaLely glve Cn. Pow do you prove lL ls group A sLrep? LaLex aggluLlnaLlon
LesL. So, mosL pus Lonslls are noL bacLerla. Lxample: lL ls group A sLrep, and 3 weeks
laLer, has bllaLeral rales, pansysLollc murmur apex radlaLlng lnLo Lhe axllla, polyarLhrlLls
dx? 8heumaLlc fever. When you do a blood culLure whaL would you flnd? noLhlng


L. Leukop|ak|a
193

W
whaL ls Lhe flrsL sLep ln managemenL? 8x

1rue ln Lhe vulva/penls area whlLe or reddlsh-whlLe plaque llke leslon LhaL does noL
scrape off flrsL sLep ln managemenL? 8x. Why? 8ule ouL dysplasla and/or lnvaslve
cancer.

I. Cancer of the mouth
MCC squamous dysplasla and cancer = smoklng
2
nd
MCC = alcohol
lf you do boLh, you lncrease Lhe rlsk of boLh.
lnvaslve squamous cancer = color change

Lower ||p cancer? Squamous ce|| carc|noma
Upper ||p? 8asa| ce|| carc|noma

veraclous carclnoma from chewlng Lobacco (squamous carclnoma), also has a Pv
vlrus assoclaLed wlLh lL.

G. PyperplgmenLaLlon dx? u&?
A AC1P AC1P
melanocyLes sLlmulaLlng properLles), very flrsL place you see hyperplgmenLaLlon ls ln Lhe
8uccal mucosa.

n. eutz-Ieghers
8loLchy (noL dlffuse) areas of hyperplgmenLaLlon. o|yps |n sma|| |ntest|ne. 1hls ls one
of Lhe excepLlons Lo rule for polyps ln Lhe small lnLesLlne. MosL polyps ln Lhe Cl locaLed
ln Lhe slgmold colon, however, polyps of euLz !eghers are locaLed ln Lhe small lnLesLlne,
and Lhey are hamarLomas, Lherefore Lhey are noL neoplasLlc, and Lhelr ablllLy Lo change
Lo cancer ls ZL8C.

II. D|seases of the Sa||vary G|ands

|eomorph|c adenoma aka Mumps ] m|xed tumor ( nC1 a LeraLoma, buL a mlxed Lumor
lL has Lwo dlff Lypes of Llssues, same cell layer). lL ls Lhe MC sallvary gland Lumor overall,
and ls ln Lhe MC locaLlon Lhe paroLld.
Mumps paramxyovlrus, lncrease ln amylase, ls Lhe lncldence of orchlLls hlgh? no, does lL
cause lnferLlllLy? no, why? 8/c lLs unllaLeral lf lL were bllaLeral Lhen lL would a much
greaLer chance. usually ln older Leenage males or male adulLs ls where orchlLls wlll occur.
Can also occur ln females - oophoerlLls MC unllaLeral, Lherefore lnferLlllLy ls rare.
194


III. D|seases of the esophagus

A. Dysphag|a and odynophg|a = d|ff|cu|ty swa||ow|ng
MosL of Lhe Llme, Lhere wlll be 3-6 clues per quesLlon. A pL has problem swallowlng
foods, ls lL sollds or llqulds?

lf Lhe pL can Lake down llqulds and noL sollds (d|ff|cu|ty |n swa||ow|ng so||ds), lL ls due to
obstruct|on can be due Lo esophageal web ln lummer vlnson syndrome, luA wlLh
glosslLls and chellosls and an esophageal web, esophageal cancer

lf pL has prob|em swa||ow|ng so||ds AND ||qu|ds, |t |s a per|sta|s|s prob|em, whlch ls
l
l
A
Scleroderma (aka progresslve sysLemlc sclerosls and C8LS1 syndrome) and achalasla.
So, Lhey wlll Lell you lmmedlaLely lf Lhey can swallow llqulds and/or sollds, or nelLher
(whlch ls a perlsLalsls problem). Pow can you dlsLlngulsh SS/C8LS1 from achalasla? ln
achalasla, Lhey vomlL up Lhe food Lhey aLe when Lhey go Lo bed aL nlghL, or Lhey wlll Lell
8 C8LS1

Cdynophg|a = AINIUL swa||ow|ng, always abnormal
ln Plv pL = Candlda esophaglLls ls lL Alus deflnlng? ?es.
MC fungal lnfecLlon ln Plv = Candlda
When lL geLs lnLo Lhe esophagus, lL ls Alus deflnlng
When lL ls a Lhrush, lL ls 8L AluS leslon (noL alds deflnlng)

ne|pfu| h|nts w|th other d|seases:
a|pab|e purpura = |mmune n type III = nenoch Schon|e|n (MC)
--2>>>Sq-#qq->-Gqv->=
ansysto||c murmur |ncreases on |nsp|rat|on = tr|cusp|d regurg
ansysto||c murmur |ncreases on exp|rat|on = m|tra| regurg

8. 1racheoesophagea| f|stu|a
8llndly endlng esophagus (prox esophagus ends bllndly) dlsLal esophagus arrlves from
Lhe Lrachea. WhaL does Lhe mom have? olyhydramnlos amnloLlc fluld ls baby urlne,
so have Lo recycle lL, or mom wlll have blg belly. So, Lhe baby swallows lL and lL ls
reabsorbed ln Lhe small lnLesLlne. So, lf you have obsLrucLlon ln Lhe esophagus, or
proxlmal porLlons of Lhe duodenum, mom wlll have polyhydramnlos. So, Lhere are 2
1 u Lhese
195

2 are assoclaLed wlLh polyhydramnlos. 1hey block Lhe ablllLy Lo reabsorb amnloLlc fluld,
leadlng Lo polyhydramnlos. Also, when Lhese klds eaL, food geLs caughL and klds cough
and spuLLer b/c Lhe dlsLal esophagus arlses from Lhe Lrachea and leads Lo dlsLenslon of
Lhe sLomach. 1hls ls very characLerlsLlc.

7&9?uu>\
Area of weakness crlcopharyngeous muscle. lL has a lll sllL ln beLween Lhe flbers of lL.
noL Lhe whole area ls cuL (whlch would be a Lrue dlverLlculum Lhls ls a false
dlverLlculum). lL goes ouL and geLs a pouch. 1he pouch collecLs food and leads Lo
hallLosls. 1hey have a Lendency of regurglLaLlng undlgesLed food ouL of Lhe nose.

D. Acha|as|a
er|sta|s|s prob prob w|th re|axat|on of the LLS, Lherefore lL ls ln spasm all Lhe Llme.
Why? lf you bx LhaL area, Lhls means LhaL Lhe gangllon cells are mlsslng. WhaL dz does
Lhls remlnd you of? n|rschsprung dz. WhaL ls ln Lhose gangllon cells? vasolnLesLlnal
pepLlde (vl). WhaL ls lLs funcLlon? 1o relax Lhe LLS. So, when you desLroy Lhose
gangllonlc cells, noL only do you desLroy Lhe movemenL of Lhe lower esophagus, buL you
also reduce vl levels. So, you have consLanL consLrlcLlon of Lhe LLS, leadlng Lo blrd
beak. rox porLlon ls dllaLed.

L. aras|tes
uz of SouLh Amerlca where Lhe lelshmanla forms lnvades Lhe gangllon cells of Lhe LLS
and Lhe recLum produce acqulred achalasla and Plrschsprung dz = 08? , vecLor
8 W
Lhe hearL? Causes myocardlLls and chronlc hearL fallure congesLlve cardlomyopaLhy.
1hls ls one of Lhe more common causes of hearL dz ln SouLh Amerlca.

I. 8arrett esophagus
ulceraLed mucosa ln Lhe dlsLal esophagus. 8x: see glandular meLaplasla, Lherefore see
gobl 1
esophagus cannoL proLecL lLself from esophageal ln[ury. 1herefore, run Lhe rlsk of
adenocarclnoma of Lhe dlsLal esophagus. Lxample: lf Lhe leslon ln esophagus, dsyphagla
of sollds, buL noL llqulds, leslon ln noLed ln dlsLal esophagus do nC1 plck squamous
cell carclnoma Lhls ls ln Lhe Mlu esophagus. lf lL ls dlsLal, lL ls adenocarclnoma, and Lhe
8

G. Lsophagea| var|ces
ullaLed submucosal esophageal velns = Lherefore pL has clrrhosls, who was an alcohollc.
L also has porLal P1n Lhe lefL gasLrlc veln ls lnvolved (one of Lhe branches off Lhe
porLal veln ls lefL gasLrlc veln). 1he lefL gasLrlc veln dralns Lhe dlsLal esophagus and
196

proxlmal sLomach. WhaL dralns lnLo Lhe lefL gasLrlc veln? Azygous veln. Where does Lhe
lefL gasLrlc veln draln lnLo? orLal veln. Powever, b/c of clrrhosls, porLal veln cannoL
empLy blood sufflclenLly lnLo lL, Lhe hydrosLaLlc pressure lncreases, you reverse blood
flow lnLo Lhe lefL gasLrlc veln, splenlc veln, and oLher velns, and end up produclng
varlces LhaL rupLure.

nematem|s|s = vomlLlng blood
nemoptys|s = coughlng up blood
nematochez|a = blood pourlng ouL of anus (acLual drlpplng of blood noL coaLlng of
sLool wlLh blood, LhaL ls seen ln anus). MCC = dlverLlculosls, noL dlverLlclullLls b/c Lhe
- W -
osls, lL ls lnLacL, and [usL have Lo erode lL, leadlng Lo 6 mL bleed.

197

n. Ma||ory We|ss Syndrome
1ear aL esophago-gasLrlc [uncLlon. Lxample
whaL does she have? 8ullmla. Classlc Lxample: alcohollc wlLh reLchlng (Lrylng Lo vomlL,
buL noLhlng ls comlng ouL causes Lremendous pressures, leadlng Lo Lear (hemaLemlsls)
8 - Lhls ls when Lhe alr geLs lnLo Lhe pleural cavlLy, and leads Lo
P
S 8

I. Lsophagea| cancer
S MCC
nd
MCC)
uysphagla seen ln Lhls pL - lnlLlally, pL cannoL swallow sollds, buL can Lake down llqulds.
Lxample: 30 y/o, male, alcohollc, wL loss, prob swallowlng foods, noL llqulds dx?
Lsophageal cancer squamous cell carclnoma of Lhe mld-esophagus (play odds).
Lxample: plc of Lrachea and see carLllage rlngs, and elasLlc arLery (esophageal ln mlddle)
Lhls ls esophageal cancer.

IV. D|seases of the Stomach

A. Congen|ta| y|or|c Stenos|s
Lxample: male, 3 weeks old and sLarLed vom|t|ng non b||e sta|ned f|u|d at 3 wks,
palpaLed Lhe abdomen and felL a knoL ln 8uC and see hyperperlsLalsls. 1hls ls nCn blle
sLaln fluld aL 3 weeks. CongenlLal ylorlc SLenosls

What |f |t |s duodena| -- S#-D 1haL would be at b|rth vom|t|ng of blle
sLalned fluld. And double bubble slgn aLresla (lack of developmenL of Lhe lumen) ls
dlsLal Lo where Lhe blle ducL comes ln, so blle can sLlll enLer Lhe proxlmal porLlon of Lhe
duodenum Lhls ls why lL ls blle sLalnlng b/c Lhere ls no movemenL, Lhere wlll be alr
Lrapped ln Lhere, and alr ls Lrapped ln Lhe sLomach, Lherefore Lhere ls alr ln Lhe sLomach
and prox duodenum a double bubble slgn. Also, mom wlll have polyhydramnlos. So,
do n
duodenal aLresla.

lL does have mulLlfacLorlal lnherlLance, Lherefore lL can be lncreased ln fuLure chlldren.
Can see pylorlc sLenosls, as lL has Lhlckened. 1o 8x, spllL Lhe muscle (called pyloroplasLy).

8. NSAID u|cers
non sLeroldal wlll block CL2, whlch ls responslble for Lhe mucous barrler of Lhe
sLomach, and vasodllaLaLlon of Lhe vessels, mucous secreLlon, and secreLlon of blcarb
lnLo Lhe mucous barrler. So, when you Lake nSAluS for a perlod of Llme, Lhe whole
198

Lhlng ls desLroyed. Leads Lo mulLlple ulcers and slgnlflcanL blood loss over Llme. 1hey
are punched ouL.

C. n. py|or|
S||ver sta|n (as |s C, Leg|one||a, bartene||a hens||a|). Comma shaped organlsms (llke
campylobacLer), buL found ouL LhaL Lhey have dlfferenL cell walls and eLc. nasLy bug b/c
lL make loLs of cyLoklnes and urease whlch converLs urea Lo ammonla, and ls one of Lhe
reasons why Lhey can burrow Lhrough Lhe mucous layer ammonla ls very Loxlc Lhls ls
Lhe LesL we use when we Lake bx of gasLrlc mucosa, we do a urease LesL on lL and lf lLs
poslLlve, know P pylorl ls ln lL. Can also use serologlcal LesLs A l
W 8 A y and, Lherefore cannoL dx
A
A

Where does pern|c|ous anem|a h|t? 8ody and fundus. 1haL ls where Lhe parleLal cells
A desLroylng Lhem, and ll leadlng Lo aLrophlc gasLrlLls.

1hls ls nC1 where P pylorl exerLs lLs affecL. n py|or| affects the py|orus and antrum. lL
desLroys Lhe mucosa, leadlng Lo aLrophlc gasLrlLls of Lhe pylorus and anLrum. 1hls ls
where cancers are. MosL cancers are along Lhe |esser curvature of the py|orus and
antrum (exacL same place where gasLrlc ulcers are). 1he P pylorl llve ln a mucous
barrler and Lherefore ls proLecLed. MCC stomach cancer = n py|or|. P pylorl can also
cause mallgnanL lymphomas of Lhe sLomach (low grade).

W 8 8
ulcers have a chance of becomlng mallgnanL Lherefore need Lo blopsy gasLrlc and noL
duodenal ulcers. Cnly reason Lhey bx a gasLrlc ulcer ls b/c Lhey are Lrylng Lo rule ouL
wheLher lL ls cancer (mallgnanL) or noL
benlgn mallgnanL. never have Lo bx a duodenal ulcer, so [usL leave alone. n py|or| |s
more common|y assoc w|th duodena| UD than gastr|c.

Why do you geL melana wlLh upper Cl bleeds? upper Cl = anyLhlng LhaL ls a bleed from
Lhe llgamenLum of LrleLz where Lhe duodenum hlLs Lhe [e[unum and up. Why ls lL
black? Acld acLs on Pb and converLs lL Lo hemaLln. PemaLln ls black plgmenL, leadlng Lo
melana. 1hls ls lmp Lo know, b/c lf you have black Larry sLools, and lLs 93 chance LhaL
ls an upper Cl bleed, and lf you play odds, lL ls prob a duodena ulcer (vs. a gasLrlc ulcer).
So, Pb ls converLed by acld Lo hemaLln, whlch ls a black plgmenL. vomlLlng of coffee
ground maLerlal = blood cloLs acLed upon by acld and changes Lo hemaLln.

199

Lxample: L, an execuLlve under greaL sLress, and sudden onseL of severe eplgasLrlc
paln LhaL radlaLes lnLo Lhe lefL shoulder. llrsL sLep ln work up? llaL plaLe of Lhe
abdomen, see alr under dlaphragm. Cdds? uuodenal ulcer. Why dld he have shoulder
paln? Alr goL ouL, seLLled under Lhe dlaphragm, lrrlLaLed nerve #4 (phrenlc), and goL
referred paln Lo Lhe dermaLome (whlch ls Lhe same dermaLomes)

D. kh|n|t|s |ast|ca: Adenocarc|noma of the stomach
WlLh slgneL rlng cells. Lxample: 32 y/o female wlLh welghL loss and eplgasLrlc dlsLress.
She had an upper gasLrolnLesLlnal serles, noLed LhaL sLomach dld noL move (no
perlsLalsls), and Lhen she dled. ux? 8hlnlLls plasLlca cells LhaL are lnvadlng Lhe wall of
Lhe enLlre sLomach, called s|gnet r|ng ce||s (whlch are sLalned wlLh mucocarnlne cells,
are plnk slgneL cells are llke a dlamond rlng, and Lhe dlamond has been pushed Lo Lhe
perlphery). 1he mucous ls lnslde, maklng Lhe cell look empLy, and pushlng Lhe nucleus
Lo Lhe slde ([usL llke faLLy change of Lhe llver). Powever, Lhese are mallgnanL neoplasLlc
glandular cells, and are characLerlsLlc of rhlnlLls plasLlca Lype of gasLrlc adenocarclnoma.

MlsconcepLlon: krukenberg tumor ls noL a Lumor LhaL ls seedlng ouL Lo Lhe ovary. 1hls
Lumor ls due Lo hemaLogenous spread Lo Lhe ovary. 1here ls no such Lhlng as a slgneL
rlng carclnoma of Lhe ovary (Lhere ls no prlmary cancer of Lhe ovary LhaL looks llke Lhls).
1he s|gnet r|ng ce||s came from stomach cancer that has metastas|ze to ovar|es =
krukenberg tumor.

MosL are ulceraLlve Lumors ln Lhe lesser curvaLure of Lhe pylorus and anLrum. LeaLher
boLLle sLomach very hard due Lo all of Lhe cancer cells and Lhe flbrous response Lo lL.

CasLrlc cancer ls decllnlng ln uS, oLher counLrles lL ls a prlmary cancer - !apan, b/c
smoked producLs. CLher eLhnlc cancers: nasopharyngeal carclnoma = chlna, sLomach
cancer and P1Lv 1 = !apan, 8urklLLs lymphoma = Afrlca.

lf Lhere was a nonLender mass ln lefL supraclavlcular area and pL wlLh eplgasLrlc dlsLress
one week ago dx? MeLasLaLlc gasLrlc adenocarclnoma. Cervlcal cancer can also
meLasLaslze here. LefL supraclavlcular node dralns abdomlnal organs, Lherefore
pancreaLlc cancers buL mosLly Lhe sLomach cancers meLasLaslze Lhere. 1he rlghL
supraclavlcular node meLs are from lung cancer.

V. Ma|absorpt|on
Means bad absorpLlon of everyLhlng: faLs, carbs, and proLelns. ulagnosls polnL of vlew we look
for lncreased faL ln Lhe sLool = sLeaLorrhea = screenlng LesL for malabsorpLlon.

A. Iat D|gest|on:
200

1) need llpases Lo break down faL lA
funcLlonlng pancreas.

2) need vllll of Lhe small lnLesLlne e would have Lo be a
mlle long. vllll lncrease Lhe overall absorpLlve surface wlLhouL lncreaslng Lhe lengLh. So,

lA 1 Sl wlLh vllll.

3) need blle salLs Lo emulslfy Lhe faL and break lL down Lo mlcelles (Llny parLlcles LhaL are 1
mlcron ln dlameLer) and chymlomlcrons. Lmulslfylng agenLs are many Llmes ln dlshwashers
b/c need Lo geL faL off plaLes. laL wlll come Lo Lhe surface and break up lnLo mlcelles, whlch
are easler Lo absorb.

So, need funcLlonlng pancreas, blle salLs, small lnLesLlne LhaL has vllll ln order Lo
reabsorb faL.

8||e sa|ts are made ln Lhe llver from cholesLerol. CholesLerol cannoL be degraded, lL
elLher solublllzed ln blle (Lherefore run Lhe rlsk of cholesLerol sLones) or ls converLed Lo
blle aclds. CannoL break down cholesLerol. \

8lle salL deflclency ls seen ln: a) llver dz, b) anyLhlng LhaL obsLrucLs blle flow wlll
produce blle salL def, c) bacLerlal overgrowLh can eaL and breakdown blle, d) Lermlnal
C C used for
LreaLmenL of hyperllpldemla, can produce blle salL def. 1hls ls Lhe MCA of reslns, by
blndlng and Lhen excreLlng Lhem, b/c lf you are noL recycllng Lhem, you wlll make more.
W u LuL
make more blle salLs, Lherefore need Lo suck more ouL of Lhe blood and wlll make more
LuL recepLors. 1hese drugs wlll evenLually Lake more cholesLerol ouL of Lhe blood and
l
people Laklng meds, b/c you wlll lose Lhese meds ln Lhe sLool, along wlLh blle salLs.

u ng LesL ls looklng for faL ln sLool (sLeaLorrhea) S
we have Lo flgure whlch lf Lhe 3 areas ls Lhe cause of Lhe malabsorpLlon pancreaLlc
def, blle salL def, or someLhlng wrong wlLh Lhe small bowel (MC).

8. Ce||ac Dz (sprue)
lc of small bowel leslon and a skln zlL LhaL has an assoclaLlon wlLh lL. 1hls ls cellac dz
(auLolmmune dz), and Lhe skln zlL ls dermat|t|s herpet|form|s. Ce||ac dz |s an
auto|mmune dz aga|nst g|uten wheat, esp. g||ad|n. lL ls very common and ls Lhe MCC of
malabsorpLlon ln Lhls counLry. So, when you eaL wheaL producLs, Lhe gluLen ls
201

A
A roy everyLhlng
S A
wlll cause desLrucLlon of Lhe vlllus. And Lhere are no vllll here lL ls flaL, blunLlng of vlllus
so you are noL able Lo reabsorb faL, proLelns, or carbs. 1here ls no vlllus surface. 1he
glands underneaLh are flne, however. 1he vllll are absenL. 1here ls a 100 chance of
dermat|t|s herpet|form|s assoc|at|on w|th under|y|ng ce||ac dz. Dermat|t|s
herpet|form|s |s an auto|mmune dz, and |t |s a ves|cu|ar |es|on of the sk|n looks llke
herpes of Lhe skln. 1hey wlll show plc of a dermaLlLls herpeLlformls, and wlll ask whaL
A

202

t]o[
An lnfecLlon of Lhe small lnfecLlon due Lo an organlsm LhaL you cannoL gram sLaln. 1.
whlppelll only seen wlLh LM, cannoL be culLured. See flaL blunLed vllll and foamy
macrophages n Plv
W 1 ve dlsLlncLlve AS-poslLlve
sLalns.

nIV pos|t|ve pt and acld fasL sLaln pL wlLh helper 1 cell counL of 100. Pave an acld fasL
sLaln wlLh Lhe foamy macrophages due to MAI (Lhls ls more common LhaL 18), and can
cause Wh|pp|e ||ke dz w|th ma|absorpt|on.

W
l
LreaLed wlLh anLlbloLlcs.

So, Lhere are ?0\>u&4>u&]0u >? C
chron|c pancreat|t|s (MC |n a|coho||cs 2 reasons for
malabsorpLlon ln alcohollcs a llpase def relaLed Lo chronlc pancreaLlLls, or blle salL def
due Lo clrrhosls, or boLh ln an alcohollc).

D. D|arrhea
8esL way Lo classlfy ls Lo subdlvlde lnLo 3 Lypes:
1. lnvaslve: bacLerla lnvades
2. SecreLory: Lhe bacLerla produces Loxlns and LhaL wlll sLlmulaLe cAM (or oLher
mechanlsms) causlng Lhe small bowel Lo secreLe small amounLs of lSC1CnlC fluld,
whlch ls naCl.
3. CsmoLlc: lacLase deflclency. Also produced by laxaLlves, and oLher lnborn errors of
meLabollsm.
SecreLory and osmoLlc dlarrheas are hlgh volume dlarrheas and you go frequenLly,
whereas lnvaslve dlarrhea ls a small volume dlarrhea. 8esL/cheapesL LesL Lo geL ln a pL
l nC1
because noL lnvaslve. lf Lhere are lnflammaLory cells Lhen you musL do fecal smear LesL
for campylobacLer or shlgella.

a) CsmoLlc dlarrhea (flLs ln wlLh osmoLlc waLer movemenL) ls when Lhere ls some
osmoLlcally acLlve subsLance ln Lhe bowel lumen LhaL ls sucklng waLer ouL of Lhe bowel,
causlng a hlgh volume, hypoLonlc loss of fluld. Lxample: lacLase def. = brush border or
dlsaccharldase deflclency, a brush border enzyme. ln a classlc case buL Lhey wlll noL Lell

S
203

conLalns S
lL wlll go Lo Lhe colon, and acL as desserLs Lo Lhe anaeroblc bacLerla whlch wlll eaL Lhe
lacLose and produces hydrogen gas, and oLher gases, and aclds, and geL acldlc sLools.
1he hydrogen gases causes Lhe bloaLlng, dlsLenLlon, and lncredlble exploslve dlarrhea.

b) SecreLory dlarrhea v L1LC
dlarrhea). 1hese are noL lnvaslve dlarrhea, Lherefore when you do a bowel blopsy Lhere
l
acLlvaLes a pump elLher cAM (vlbrlo) or some oLher pump: guanylaLe cyclase (L. coll).
1reaLmenL: when you glve fluld replacemenL Lo paLlenLs wlLh v. cholerae, you need Lo
glve glucose along wlLh Lhe flulds. 1hls ls b/c you need glucose Lo co-LransporL na LhaL
was ln Lhe flulds. Slde noLe: need Lo know Lhe oLher L. coll relaLed Loxlns: LPLC:
C137:P7, LlLv, and LaggLC.

c) lnvaslve dlarrhea: Lhe MC ln uS ls caused by campylobacLer [e[unl, and shlgella ls a
close second. Classlc case: a person wlLh low vlne(?) dlarrhea, wlLh some blood ln lL,
and on gram sLaln Lhere were comma shaped or S-
campylobacLer [e[unl. 8oLh of Lhese organlsms can produce pseudomembranes.
1herefore all pseudomembranes does noL necessarlly mean you wlll see C. dlfflclle.

d) araslLes LhaL causes dlarrhea:
G|ard|a: owl eyes LhaL move. 1hls ls Lhe MCC of dlarrhea due Lo a paraslLe ln Lhe uS.
1reaLmenL: meLronldazole.

Cryptospor|d|um parv|: MCC of AluS dlarrhea ls a parLlally acld-fasL organlsm. lL
sLlcks Lo Lhe wall of Lhe colon. Classlc case: Lhere ls a pL LhaL has AluS and has
dlarrhea, and when Lhey sLaln lL, Lhere are oocysLs LhaL are parLlally acld-fasL. lL
wlll klll lf you are lmmunocompromlsed. 1he LreaLmenL ls almosL worLhless. lL
comes aL Lhe end when Lhe helper 1-
Lhe organlsms LhaL wlll klll you: MAl, crypLosporldlum, Loxoplasmosls, and CMv all
comes ln aL Lhe end. . carlnll comes ln around 200 helper 1-cells.

C|ostr|d|um d|ff|c||e: 1hls ls an auLopsy plc of an older woman who was ln Lhe
hosplLal wlLh pneumonla, and she developed dlarrhea. WhaL was found on
auLopsy? Well, lL ls safe Lo say LhaL lf she had pneumonla, Lhen she was Laklng
anLlbloLlcs. So Lhls ls pseudomembranous co||t|s, caused by c|ostr|d|um d|ff|c||e.
1hls occurs when Laklng anLlbloLlcs LhaL wlpe off Lhe good organlsms, leavlng
behlnd c. dlfflclle. Lverybody has c. dlfflclle ln Lhelr sLools, buL L. coll,
enLerobacLer fragllls are keeplng lL ln check. 8uL when Laklng anLlbloLlcs such as
amplclllln (MC), cllndomycln (2
nd
MC) for a perlod of Llme, you knock off Lhe good
204

guys, glvlng c. dlfflclle a chance Lo prollferaLe and make Loxlns LhaL damage Lhe
1
1hls ls analogous Lo c. dlphLherla, whlch also has a Loxln LhaL damages and
produces pseudomembranes buL Lhe organlsm does noL lnvade. 1he rlbosylaLlon
Lhlng, and Lhe LlongaLlon facLor 2 (Ll-2 allows for proLeln elongaLlon) are messed
up, Lherefore cannoL elongaLe proLelns. 1he flrsL sLep ln managemenL ls Lo do a
Loxln assay of sLools, noL gram sLaln b/c Lhere are loLs of gram sLaln organlsms ln
Lhe sL 1he screen|ng test of
cho|ce |s tox|n assay of stoo|! 1he LreaLmenL ls Lo glve meLronldazole, used Lo
glve vancomycln b/c c. dlfflclle became reslsLanL Lo lL. MeLronldazole lLself can
produce pseudomembranous collLls buL you Lake LhaL chance.

VI. D|seases of the Sma|| Intest|ne

A. Sma|| bowe| obstruct|on: See classlc sLep ladder appearance of alr-fluld levels: alr, fluld,
alr, fluld (sLep ladder appearance). When you have a hollow vlscous LhaL perlsLalsls, you
geL a cerLaln characLerlsLlcally paln, called CCLIC pa|n l
palnfree lnLervals, collcky paln ls when you have paln, a palnfree lnLerval, paln, and Lhen
a palnfree lnLerval. 1he lnLervals are noL conslsLenL, someLlmes you have a 13 mln
palnfree lnLerval, and oLher Llmes lf may be longer or shorLer. 1hls ls collcky paln, lL
means 1C1AL small bowel obsLrucLlon. 8y Lhe way, Lhe blle ducL does noL have
perlsLalsls, Lherefore you do noL geL collcky paln, and lnsLead you geL crampy paln. ?ou
A
8
you geL sLagnaLlon of Lhe food proxlmal Lo wherever Lhe obsLrucLlon ls, and geL alr-fluld
levels. ulsLal Lo Lhe area of obsLrucLlon Lhere ls no alr. ln obsLrucLlon, Lhere are Lwo
Lhlngs LhaL can happen: const|pat|on or obst|pat|on. ConsLlpaLlon ls where you have a
problem wlLh sLoollng, whlch does noL necessarlly mean obsLrucLlon. CbsLlpaLlon
means LhaL noL only do you have consLlpaLlon you also have a problem passlng gas, LhaL
means you have compleLe obsLrucLlon. So you have Lo ask Lhe pL wheLher Lhey have
passed any sLools or gas. MCC of obstruct|on: adhes|ons from prev|ous surger|es.
Sllde: Lhose are waLermelon plLs, wlLh a narrow lumen. 8uL lf Lhe case read LhaL Lhls pL
dld noL have pervlous surgerles and had collcky paln, Lhls ls due Lo Lhe bowel belng
Lrapped ln Lhe |nd|rect |ngu|na| hern|a. Lxample: Lhere was a welghL llfLer who
developed collcky paln ln Lhe 8LC area, had no prevlous surgery, Lhe mosL llkely cause ls
lndlrecL lngulnal hernla. WelghL llfLers ofLen Llmes creaLe lndlrecL lngulnal hernlas.

S|de note: Lhere was a plc of DowS kld. 1rlsomy 21 (abnormal number of
chromosomes) ls due Lo nondls[uncLlon (unequal separaLlon durlng Lhe flrsL sLage of melosls l)
8
205

kobertson|an trans|ocat|on. ln Lhls case, Lhey would have 46 chromosomes buL on one of
Lhose chromosomes 21, wlll be anoLher chromosome aLLached Lo lL. 1hey wlll have Lhree
1 Cl MC u duodena|
atres|a (double bubble slgn) and n|rschsprung dz.

8. n|rschsprung dz: Lhe nerves are Lhere buL Lhe gangllonlc cells are mlsslng. So, whaL

openlng, b/c Lhere ls no perlsLalsls. So Lhe sLools [usL sLay Lhere. So, Lhe dllaLlon of Lhe

sLools Lhru Lhe recLal area. So Lhls means LhaL Lhe recLal ampulla has no sLools ln lL.
Lxample: lf
exam was performed. lf Lhere was NC stoo|s that came out on exam |t means
n|rschsprung dz. lf on exam, Lhere was sLools on Lhe flnger, lL means LlghL sphlncLer.
1h|s |s a dz of the co|on.

C. Intussuscept|on:
goes lnLo Lhe cecum. 1here wlll be collcky paln b/c you are obsLrucLlng, and noL only
LhaL, you are compromlslng blood flow, so you geL Lhe bleedlng. 1hey wlll say: a 2 y/o
kld, wlLh collcky paln and bloody sLools. 1hey mlghL way Lhere ls an oblong mass ln Lhe
8uC. ln some klds, lL sponLaneously comes ouL, buL lf noL, Lhen Lhe radlologlsLs wlll do
barlum enema, and puL a llLLle pressure Lhere, and he reverLs lL. So you geL compleLe
bowel obsLrucLlon and lnfarcLlons.

D. Vo|vu|us: 1
compleLe obsLrucLlon and lnfracLlons due Lo compromlslng blood flow.

L. Ga||stone ||eus usually seen ln older people, more women, and have slgns of collcky
paln, and obsLrucLlon. 1he gallbladder sLone falls Lhru Lhe flsLula and seLLles lnLo Lhe
lleocecal valve and causes obsLrucLlon. See a flaL plane of Lhe abdomen LhaL produced
alr ln Lhe bll 8 u 1here ls a flsLula LhaL ls communlcaLlng
Lhe gallbladder wlLh Lhe small bowel Lherefore alr can geL ln Lhe small bowel and Lhe
blllary Lree. A|r |n the b|||ary tree w|th co||cky pa|n |s ga||stone ||eus. Dz of ga||b|adder.

I. Mecon|um I|eus = cyst|c f|bros|s

VII: D|seases of the Co|on

A. Vascu|ar d|seases of the co|on:

1. Ischem|c 8owe| Dz:
206

1he small bowel more commonly lnfracLs Lhan Lhe large bowel, b/c lL has only one
blood supply. 1he enLlre small bowel, Lhe ascendlng colon, and Lhe Lransverse colon
are all supplled by Lhe SMA (superlor mesenLerlc arLery). So, whaL ls Lhe maln dlff ln
a small bowel lnfarcL vs. an lschemlc ulcer causlng bloody dlarrhea ln Lhe splenlc
flexure? 1he dlfference ln resenLaLlon. 1hey boLh can have bloody dlarrhea.
Powever, Lhe sma|| bowe| |nfarct|on wlll ullluSL abdomlnal paln (all over noL one
speclflc area). ln |schem|c co||t|s, lL wlll polnL Lo speclflc area on rlghL slde of
abdomen. 1hls dlfferenLlaLes bLwn a small bowel lnfarcL from a small lnfarcL ln Lhe
colon (can plnpolnL area).


2. Ang|odysp|as|a
2
nd
MCC nematochez|a l
Laplace (wall sLress and radlus). 1he dlameLer of Lhe cecum ls blgger Lhan any oLher
parL of Lhe colon. 8/c Lhe dlameLer ls greaLer, Lhe wall sLress ls greaLer. 1herefore,
puLLlng sLress on Lhe vessels ln Lhe wall of Lhe cecum, lL acLually pulls Lhem aparL and
produces LelanglecLaslas. As a resulL, lL predlsposes Lo anglodysplasla b/c lncreased
wall sLress. lf one of Lhem rupLures Lo Lhe surface, you can end up wlLh slgnlflcanL
bleed. A very common cause of PemaLochezla ln older people. So, lf dlverLlculosls ls
ruled ouL, anglodysplasla ls probably lL.

7)9>?uu>\9L\>> Intest|ne Dz:
Iq>kSk
cm ln lengLh, 2 y/o or younger, and 2 of carclnold Lumors occur ln M.u.

MC compllcaLlon = bleedlng. 8/c lL ls a dlverLlculum, lL can be lnflamed, and leads Lo
dlverLlcullLls. Lxample: hematem|s|s, pa|n |n kL area, me|ana M
melana Anu hemaLemlsls uC C

Lxample: newborn wlLh a slnus and umblllcus was dralnlng poop dx? erslsLenL
vlLelllne ducL someLlmes lL ls open all Lhe way Lhrough, Lherefore
Lhere ls a communlcaLlon beLween Lhe small bowel and umblllcus, so feces comlng ouL
of umblllcus, whlch ls perslsLence of Lhe vlLelllne ducL. lf you have urlne comlng ouL of
Lhe vlLelllne ducL, Lhls ls perslsLence of Lhe uracus. So, feces=v|te|||ne duct, ur|ne =
uracus.

C. S|gmo|d Co|on
MC locaLlon for cancer ln Lhe enLlre Cl LracL = slgmold colon
MC locaLlon for polyps ln Lhe enLlre Cl LracL = slgmold colon
MC locaLlon for dlverLlcula ln Lhe enLlre Cl LracL = slgmold colon
207


1he area of weakness ls where Lhe blood vessels peneLraLe Lhe valve. 1he mucosa and
1
When feces are sLuck (fecallLh), can erode LhaL vessel, and can see why d|vert|cu|os|s |s
the MCC of nematochez|a mass|ve |ower GI b|eed. 1hese exLend ouLslde of Lhe
lumen, whlch ls dlverLlculosls. lf you see polyps ln Lhe lumen, do noL confuse wlLh
polyposls po|yps go IN1C the |umen, noL ouL.

D. D|vert|cu|os|s
MC comp||cat|on = d|vert|cu||t|s, has MAn? compllcaLlons.

D|vert|cu||t|s L 8LC M8
Lenderness, fever, and neuLrophlllc leukocyLosls) Lhls ls Lhe same presenLaLlon ln
dlverLlcullLls), buL dlverLlcullLls occurs ln Lhe LLC area, ln an elderly person. MCC f|stu|as
commun|cat|ons |n the GI = d|vert|cu|os|s. WlLh a flsLula, Lhere ls communlcaLlon
beLween 2 hollow organs. 1he MC f|stu|as are co|oves|c|e f|stu|aS , whlch ls a flsLula
beLween Lhe colon and Lhe bladder, leadlng Lo neumatur|a a|r |n the ur|ne. MCC of
co|oves|c|e f|stu|a |s d|vert|cu|ar dz. 1hey can rupLure, and Lhe rupLure can cause
perlLonlLls.

<aaa7a&o>\\>40&?&?
Croh lnvolved Lhe Lermlnal lleum 80 of Lhe Llme. SomeLlmes lL [usL lnvolves Lhe
Lermlnal lleum, someLlmes lL lnvolves Lhe Lermlnal lleum Anu Lhe colon, and someLlmes lL
[usL lnvolves Lhe colon. C llkes Lhe AnuS, uC llkes Lhe 8LC1uM (Lhey have a
preference for whlch parL of Lhe lower parL Lhey llke). C llkes Lo produce flsLulas and
flssures of Lhe anus, uC llkes Lhe recLum, produclng bloody dlarrhea. C [umps
around, Lransmural, noncaseaLlng granulomas. uC lnulLy, and
lnvolves Lhe mucosa/submucosa. Dx of qS |s s|mp|e |e ||eoceca| va|ve, ascend|ng
co|on, term|na| ||eum there |s a transmura| |nf|ammat|on w|th a very narrow |umen
therefore the presentat|on w||| be co||cky, kL pa|n, w|th d|arrhea |n young person.
Noth|ng except qS produces co||cky pa|n |n the kL |n a young person! lf ls a 3
rd

world counLy, whaL ls lL? 18 (m. bovls). ln Lhls counLry, lf we geL lnLesLlnal 18 from
swallowlng lL and lL wlll be M .1b. ln Lhlrd world counLrles, lL produces presenLaLlon same
as C Lhls occurs b/c Lhey do noL have pasLeurlzaLlon, M. bovls ls Lhe MCC, Lhls ls
Str|ng s|gn on barlum sLudy, looks llke a sLrlng see LhaL lL ls
Lransmural and LhaL lL ls segmenLal. 1he proxlmal valve ls dllaLed have Lo push sLool
S C dz. Llnear ulcers
are apLhus ulcers. Non caseat|ng granu|oma |s character|st|c of UC. UC a|ways beg|ns |n
the rectum, can sLay Lhere, or can move up ln conLlnulLy and lnvolved Lhe whole colon, buL
lL never lnvolves Lhe Lermlnal lleum. lL ls lnvolves Lhe whole colon, lL ls called pancollLls, and
208

Lhls has Lhe hlghesL lncldence of cancer. So, Lhe more lnvolvemenL and greaLer duraLlon =
greaLer chance of cancer relaLed Lo uC. seudopolyps see ulceraLed mucosa and
submucosa. seudopolyps are resldual polyps LhaL are lnflamed, lL ls lnflamed bloody
mucosa. LveryLhlng ls ulceraLed off, and you see Lhe submucosa of Lhe colon. uC has Lhe
hlghesL lncldence wlLh cancer, PLA 827 anklyosls spondyllLls, and ls Lhe MCC of scleroslng
perlcholanglLls (sclerosls/flbrosls around common blle ducL, produclng obsLrucLlve [aundlce
and hlgh lncldence of cholanglocarclnoma). know Lhe dlff ln uC vs. C.

Ik. 1umors of the Co|on o|yps
MC po|yp |n ent|re GI = hyperp|ast|c po|yp lL ls a llLLle nubbln aka hemarLomas
(Lherefore noL neoplasLlc), usually ln slgmold colon.

1ubu|ar adenoma: looks llke a sLrawberry on sLlck, Lherefore has a sLalk wlLh
sLrawberry, whlch ls Lhe precursor leslon for colon cancer.

Iuven||e o|yp S kld wlLh polyp ln recLum, a|| [uven||e
po|yps |ocated |n the rectum and are hamartomas (no precancerous).

LeLs say lL ls an adulL and Lhe polyp ls sLlcklng ouL (a reddlsh mass) dx? Interna|
hemorrho|ds. ku|e: |nterna| hemorrho|ds b|eed, externa| hemorrho|ds thrombose.
1herefore, when you have blood coaLlng Lhe sLool, lL ls lnLernal hemorrhold. lnLernal
hemorrholds are nC1 palnful, buL Lhey do prolapse.
AdulL wlLh someLhlng reddlsh sLlcklng ouL of Lhelr buLL = prolapsed lnLernal hemorrhold.
Interna| hemorrho|ds b|eed and pa|n|ess, wh||e externa| thrombose and are pa|nfu|.

Sess||e o|yp (v|||ous adenoma) looks llke Lhe vlllous surface of Lhe small lnLesLlne
(hence name vlllous adenoma), Lhese are lll flnger-llke excrenses of Lhe small lnLesLlne,
hence Lhe name vlllous adenoma. 1hese have the greatest ma||gnant potent|a|, and
are usua||y |n the recta| s|gmo|d. 8/c Lhey are vlllous/flnger llke Lhey have a loL of
mucous coaLlng Lhe sLool, mucous secreLlng vlllous. 1hey have a 30 chance of
becomlng mallgnanL. So, Lubular adenomas are precursors for cancer (slze deLermlnes
mallgnanL poLenLlal lf Lhey are above 2 sonomeLers, Lhey are very dangerous) and
vlllous adenomas lead Lo cancer, Loo.

Iam|||a| po|ypos|s need Lo have over 100 polyps Lo have famlllal polyposls. 1hls dz ls
auLosomal domlnanL, uses AC suppressor gene, ras, and p33, AC ls Lhe ma[or one.
Wlll always geL cancer ln Lhem, usually beLween 33-40. 1herefore, wlll need Lo
prophylacLlcally remove Lhe bowel. 1he auLosomal domlnanL dz ls famous for laLe
Au 1
means LhaL Lhey wlll noL be born wlLh polyps aL blrLh (Lhey sLarL developlng bLwn Lhe
209

ages of 10-20, ln Auku, Lhey do noL have cysLs are blrLh, Lhey sLarL developlng bLwn
10- P -40 years, and
Lhey have laLe manlfesLaLlons.

Affected co|on has po|yps and bra|n tumors = 1urcot syndrome (llke Lurban)
Lherefore, you have a polyposls syndrome wlLh braln Lumor, Lhls dz ls auLo rec (noL
domlnanL).
l&? &\ : Pave mulLlple polyps ln Lhere, plus b9 salL Llssue Lumors:
desmolds and osLeomas ln Lhe [aw.

k. Carc|no|d 1umors
Along wlLh aupuL Lumors. All carclnold Lumors are mallgnanL, buL have low grade poLenLlal.
A loL of lL depends on Lhelr slze and lf Lhey are golng Lo meLs. uepends on Lhelr slze ln
sonomeLers lf Lhey are greaLer Lhan 2 sonomeLers Lhey have Lhe ablllLy Lo meLs. MC
|ocat|on for carc|no|d tumor = t|p of the append|x have a brlghL yellow color, buL Lhey
are NLVLk the cause of carc|no|d syndrome why? 8/c Lhe Llp of Lhe appendlx wlll never
be greaLer Lhan 2 sonomeLers. So, where ls Lhe MC |ocat|on of carc|no|d tumor that CAN
be assoc|ated w|th carc|no|d syndrome? 1erm|na| I|eum they are a|ways greater than 2
sonometers. WhaL do all carclnold Lumors make? Seroton|n. 8/c Lhe appendlx and
Lermlnal lleum are dralned by Lhe porLal veln, Lhe seroLonln made goes Lo Lhe porLal veln,

Lherefore lL ls noL ln Lhe bloodsLream. 1herefore, Lhere are no slgns of flushlng and
dlarrhea b/c Lhere ls no conLacL wlLh Lhe sysLemlc clrculaLlons. Powever, lf you meLs Lo Lhe
llver, Lhen Lhose meLasLaLlc nodules LhaL are maklng seroLonln can dump some of lL lnLo
Lhe hepaLlc veln LrlbuLarles. 1hls does have access Lo Lhe sysLemlc clrculaLlon b/c goes Lo
lvC Lo 8lghL slde hearL, and Lhls ls why you geL rlghL slded leslons 1lS
and pu|mon|c stenos|s. Seroton|n ls a vasodllaLor ln some cases, buL a vasoconsLrlcLor ln
oLher cases. Powever, ln Lerms of seroLonl that causes
f|ush|ng (wh|ch |s the MC symptom of carc|no|d), fo||owed by d|arrhea (2
nd
MC). lf lL has
access Lo sysLemlc clrculaLlon, lL has hlgh levels of 3 hydroxyaceLoaclLlc (?) acld, whlch ls Lhe
screenlng LesL of cholce b/c lL ls Lhe meLabollLe of seroLonln. So, b]c mak|ng and LCSING a
|ot of seroton|n, what aa can be def|c|ent? 1ryptophan |s def, therefore the v|tam|n
N|ac|n |s def, therefore can have pe||agra. ou us|ng up a|| the 1ryptophan and mak|ng
seroton|n |nstead of n|ac|n.

kI. Co|on cancer
neurosecreLory granules on LM colon cancer, |eft s|de obstructs, r|ght s|de b|eeds.

1hls ls easy Lo undersLand b/c Lhe lefL colon has a smaller dlameLer Lhan Lhe rlghL. So,
when Lhe cancer develops ln the |eft co|on and wanLs Lo form a polyp, lL goes around
210

annu|ar (napk|n r|ng), and produces consLrlcLlon. Cpen bowel ln lefL colon, see one edge
of Lhe cancer on each slde of Lhe bowel and bowel ls consLrlcLed have slgns of obsLrucLlon
(lefL slde obsLrucLs, rlghL slde bleeds).

ln Lhe r|ght co|on, b/c of Lhere ls a blgger dlameLer, lL has a blgger chance of golng ouL and
formlng a polyp. 1herefore, lL ls slLLlng ln Lhe sLool, leadlng Lo a bleed (Lherefore lefL slde
obsLrucLs, rlghL slde bleeds).

So, whlch ls slde ls more llkely Lo have le def? 8lghL slded leslon.
Whlch ls more llkely Lo have alLeraLlon ln bowel hablLs (consLlpaLlon/dlarrhea)? LefL slded.

1umor marker for co|on cancer = CLA (carc|noembryon|c Ag). noL used Lo dx colon cancer,
buL used Lo follow lL for 8LCCCu88LnCL. MCC relaLes Lo dleL (lack of flber ln sLool
Lherefore, more flber you have, Lhe less chance of colon cancer b/c you are geLLlng rld of
llpocollc acld). Age ls also a rlsk facLor (pLs over 30), smoklng ls a rlsk facLor LhaL ls assoc
wlLh colon cancer. olyposls coll syndromes also have an assoclaLlon (famlllal polyposls,
C
nC1 euLz !eghers, hyperplasLlc polyps, or [uvenlle polyps).



kII. D|seases of the Append|x: Append|c|t|s

Covered wlLh pus, MCC appendlclLls ln adulLs = fecallLh = lmpacLed sLool. So when you
lmpacL sLool lL presses on Lhe sldes of Lhe appendlx, and leads Lo lschemla, Lhen geL a
breakdown of Lhe mucosa, L. coll geLs ln Lhere and acuLe appendlclLls occurs. 1h|s |s the
SAML mech for d|vert|cu||t|s (Lhe dlverLlcular sacs also geL fecallLhs ln Lhem and Lhe same
exacL Lhlng happens Lhe paLhogenesls of acuLe dlverLlcullLls and acuLe appendlclLls ls
exacLly Lhe same). So, fecallLh, lschemla along Lhe wall, lnflammaLlon, L coll.

AnoLher analogy: acuLe cholecysLlLls excepL lL ls noL a fecallLh, buL ls a sLone ln Lhe cysLlc
ducL pushes on Lhe slde, leads Lo lschemla, acuLe cholecysLlLls, L coll. So, Lhere ls a concepL
Lhere we have acute cho|ecyst|t|s, d|vert|cu||t|s, and append|c|t|s a|| re|ated to
someth|ng obstruct|ng the |umen, caus|ng mucosa| damage, and L co|| |nf|ammat|on. ln

fecallLh.

WhaL Lhe MCC of append|c|t|s |n ch||dren? Meas|es and]or adenov|rus |nfect|on. 1hen,
acuLe appendlclLls occurs b/c Lhere ls lymphold Llssue ln Lhe appendlx. WlLh measles or
adenovlrus lnfecLlon, geL hyperp|as|a of |ympho|d t|ssue |n the append|x, and can obstruct
211

the |umen and set up |nf|ammat|on for mucosa| |n[ury and |eads to acute append|c|t|s.
So, |n ch||dren, |t usua||y fo||ows a v|ra| |nfect|on. As opposed Lo adulLs, where lL ls due Lo
fecallLh.
212

CnA1Lk 10. LIVLk

I. 8|||rub|n metabo||sm:

MosL of Lhe blllrubln ln our blood 88C
are old, phagocyLosed and desLroyed. uncon[ blllrubln ls Lhe end producL, goes Lo Lhe
bloodsLream and blnds wlLh albumln, goes Lo Lhe llver and ls Laken up. Ma[orlLy of blllrubln
ls from breakdown of 88C none of Lhls ls ln Lhe urlne b/c lL ls
llpld soluble. So, lL geLs Laken up by Lhe llver and ls con[ugaLed. Any Llme Lhe cyLochrome
p430 con[ugaLes blllrubln, or meLabollzes any drug, lL renders lL waLer soluble. So, we have
a llpld soluble uncon[ugaLed blllrubln ls converLed Lo con[ugaLed blllrubln (dlrecL blllrubln),
whlch ls waLer soluble. Cne of Lhe purposes of Lhe llver ls Lo render llpld soluble drugs
waLer soluble, so you can pee Lhem ouL. So, we con[ugaLe lL and have waLer soluble
blllrubln. Cnce blllrubln ls Laken up by Lhe llver, lL ls never close Lo a vessel. So, Lhere ls no
way lL can geL lnLo a vascular channel (once lL ls Laken up by Lhe llver). So, lf dlrecL
con[ugaLed blllrubln ls ln our urlne, Lhls ls b/c someLhlng happened (elLher ln Lhe llver or
.
So, lL ls Laken up ln Lhe llver, con[ugaLed, and pumped lnLo Lhe blle ducLules, whlch go lnLo
Lhe Lrlad, goes up Lhe common blle ducL, some ls sLored ln Lhe C8 and goes lnLo Lhe small
lnLesLlne Lhrough Lhe common blle ducL. 1herefore, blle conLalns con[ugaLed blllrubln. lLs
also conLalns blle salLs, cholesLerol and esLrogen, buL has con[ugaLed blllrubln LhaL we wlll
geL rld of. So, Lhls con[ugaLed blllrubln Lakes a long Lrlp down Lo Lhe colon and Lhe bacLerlal
have been walLlng for Lhe con[ugaLed blllrubln and wlll break lL down back lnLo
uncon[ugaLed blllrubln. 1hen, lL conLlnues Lo break lL down. 1he bacLerla breaks lL down Lo
sLercoblllnogen (whaL lL used Lo be called). SLercoblllnogen oxldlzes Lo sLercobllln produces
Lhe color of sLool. 1hls Lerm ls no longer used. now, lL ls called uroblllnogen (whlch makes
Lhe color of Lhe plgmenL). lL ls easler Lo undersLand Lhe concepL. So, the uncon[ugated
b|||nogen |s broken down to urob|||nogen. All porphyrlns are colorless when Lhey are ln an
- S urob|||nogen,
when |t becomes ox|d|zed |n the stoo| becomes urob|||n, wh|ch |s the co|or of stoo|. A
small porLlon of uroblllnogen ls reabsorbed ouL of Lhe colon. MosL of lL goes back Lo Lhe
llver. A llLLle of lL goes Lo Lhe kldney and ends up ln Lhe urlne, where lL geL oxldlzed lnLo
urobllln. 1hls ls Lhe cause of Lhe color of urlne. So, the same p|gment that co|ors stoo| |s
respons|b|e for co|or|ng ur|ne. We were LaughL LhaL sLercoblllnogen ls ln Lhe sLool and
uroblllnogen ls ln Lhe urlne, however, sLerco = uro, so Lhe same compound ls responslble
for color change ln feces and urlne. 1hey are noL dlff plgmenLs, Lhey are Lhe same. So, lf
you have obsLrucLed blle flow (ln Lhe llver or C8u), whaL should Lhe color of Lhe sLool be?
LlghL colored b/c Lhe uroblllnogen would noL have access Lo Lhe sLool Lo color lL. Also,
would noL have uroblllnogen ln Lhe urlne. 1hls leads Lo [aundlce.

213

II. Iaund|ce
1o calculaLe [aundlce, Lhey Lake Lhe LoLal blllrubln and flnd ouL Lhe percenLage of blllrubln
LhaL ls con[ugaLed (dlrecL blllrubln). Lxample: LoLal ls 10, con[ = 3, Lherefore con[ blllrubln =
30. So, Lhey subdlvlde [aundlce lnLo 3 Lypes con[ugaLed blllrubln less Lhan 20
(Lherefore mosL of lL ls uncon[ugaLed),
bLwn 20-30 (Lherefore some ls con[ and uncon[), and
greaLer Lhan 30 (mosL of lL ls con[ugaLed blllrubln). lLs also means LhaL you have
obsLrucLlon.

lf lL ls under 20, Lhls pr|mary uncon[ugated hyperb|||rub|nem|a. So whaL can lncrease
uncon[ blllrubln? nemo|yt|c anem|as, spherocytos|s, SCDz, A8C hemo|yt|c dz of the
newborn, kh hemo|yt|c dz of the newborn, phys|o|og|c [aund|ce of the newborn (b/c Lhey
cannoL con[ugaLe lL). So, Lhere ls lncreased uncon[ugaLed blllrubln b/c breaklng down more
88C elLher Loo lmmaLure or Lhey are mlsslng
enzymes (Cra|g|er Na[[ar syndrome). So, we are elLher maklng Loo much b/c we are
88C whlch ls

deflclenL ln Lhe enzyme (Cralgler na[[ar).

1 btwn 20- S0 are hepaLlLls. nepat|t|s = lnflammaLlon of Lhe llver (noL [usL some of
S .
uncon[ llver bullds up behlnd Lhe llver. lnflammaLlon ln Lhe llver wlll maybe desLroy Lhe
archlLecLure ln Lhe llver and break open blle ducLs LhaL have con[ blllrubln ln Lhem. now,
b/c you have dlsrupLed Lhe archlLecLure, Lhere ls a posslblllLy of waLer soluble blllrubln Lo
geL lnLo Lhe blood sLream (b/c Lhere ls necrosls of llver cells and blle ducLs so you wlll geL
con[ugaLed blllrubln ln Lhere, Loo) - leadlng Lo 20-30. 1hls |nc|udes a|| the hepat|t|s
(|nc|ud|ng a|coho||c).

lf lL ls greater than S0, Lhls ls a nC 88AlnL8 lL ls clearly an obstruct|on of b||e. We have
lnLrahepaLlc obsLrucLlon (|ntrahepat|c cho|estas|s), meanlng LhaL you are blocklng blle flow
ln Lhe llver (Lrlad ls blocked). Also have extrahepat|c cho|estas|s (ouLslde of Lhe llver).
1here ls only one Lhlng ouLslde Lhe llver LhaL can lead Lo Lhls C8D (common b||e duct).
1herefore, someLhlng ls obsLrucLlng LhaL a sLone ln Lhe common blle ducL LhaL came from
Lhe C8 (play odds). Can also have carclnoma of Lhe head of Lhe pancreas b/c ducLs go
Lhrough Lhe head of Lhe pancreas. As a resulL, you have compleLe blle ducL obsLrucLlon.
So, Lhere ls lnLrahepaLlc cholesLasls and exLrahepaLlc cholesLasls. So, whaL wlll happen ls
llke waLer behlnd a dam. lf you block blle flow, lL wlll back up where does lL back up?
8acks up Lo where lL was made (Lhe llver cells remember Lhls ls an excess of con[ugaLed,
dlrecL blllrubln). ln Lhe llver cells, lL bubbles ouLslde, and has access Lo Lhe slnusolds and
now ls ln Lhe blood sLream. So, Lhe predomlnanL facLor ln Lhe blood sLream ls
214

CCNIUGA1LD b|||rub|n, whlch ls waLer soluble. So, wlll have very dark ye||ow ur|ne and
the stoo| w||| be LIGn1 co|ored. 1hls combo h|gh con[ b|||rub|n, b|||rub|n |n the ur|ne
PAS aLer soluble), and ||ght co|ored
stoo|s = C8S1kUC1ICN (noLhlng else can do Lhls, and lL ls elLher lnLrahepaLlc or
exLrahepaLlc).
A. Congen|ta| Uncon[ugated hyperb|||rub|nem|as

IL->S
Seen lf you fasL for over 24 hrs and geL [aundlce, Au, b9 (Lherefore do noL need a bx).
Mech: prob |n tak|ng up b|||rub|n and prob |n con[ugat|ng b|||rub|n, Lherefore lL ls
predom|nant|y an uncon[ugated hyperb|||rub|nem|a. So, lf you wanL Lo see lf pL has
lL, do 24 hr fasLlng LesL. So, geL basellne blllrubln when Lhey are noL [aundlced and
W L
C
syndrome. Lx. pL comes back afLer fasLlng LesL and ls 2.3.

2
nd
MCC [aund|ce = G||berts syndrome (MC = hep A). Lx. resldenL LhaL geLs [aundlce,
C
normal, hlgh uncon[ blllrubln levels). 8x? noLhlng
2. Cra|g|er Na[[ar

8. Congen|ta| Con[ugated hyperb|||rub|nem|as

Dub|n Iohnson, kotor syndromes C CCn!
blllrubln ln Lhe blle ducLs. So, Lhls ls predom|nant|y a con[ hyperb|||rub|nem|a. ln
uublln !ohnson, have a black colored plgmenL LhaL bullds ln Lhe llver and geL black llver.

III. L|ver Iunct|on 1est (LI1s)

WhaL are transam|nases used for? 1hey are |nd|ces of ||ver ce|| necros|s (hepaLlLls). AS1
(SCC1) and AL1 (SC1), AL1 ls more speclflc b/c lL ls only found ln Lhe llver, AS1 ls ln
88C

1herefore, lf you have a v|ra| hepat|t|s, wlLh masslve llver cell necrosls, whlch would be Lhe
predomlnanL Lransamlnases elevaLed? AL1. Lx: 2300 AL1 and 2200 AS1. So AL1 wlll be Lhe
maln llver cell enzyme e|evated |n d|ffuse ||ver ce|| necros|s.

ln a|coho||c hepat|t|s, Lhls ls noL whaL happens. 1here ls a reason: AS1 ls presenL ln Lhe
mlLo of hepaLocyLes. AL1 ls noL A
LhaL lL uncouples). AS1 ls predomlnanLly ln mlLo, and when pL has alcohollc hep, AS1 |s
215

h|gher than AL1 (forgeL Lhe 2:1 relaLlonshlp). 1herefore, lf you see AS1 hlgher Lhan AL1,
Lhls ls due Lo alcohollc llver dz. Could be faLLy change, alcohollc clrrhosls, and alcohollc
hepaLlLls l vl8AL paLlLls, AL1 ls blgger Lhan AS1.

So, whaL are Lhe enzymes of C8S18uC1lCn (obstruct|on of b||e ducts)? A|ka||ne
phosphatase and Gamma g|utamy| transferase. 1ransamlnases wlll also be up, buL noL Lo
Lhe same degree. Camma gluLamyl Lransferase ls locaLed SL8 W SL8
up, lL undergoes hyperplasla (le due Lo drugs: alcohol, barbs, rlfampln, and phenyLoln), you
noL only lncrease Lhe meLabollsm of Lhe drug, buL also lncrease Lhe synLhesls of gamma
gluLamyl Lransferase. So, whaL would Lhe classlc Lhlng you would see ln any a|coho||c ||ver
dz? AS1>AL1, a|ong w|th INCkLASLD gamma g|utamy| transferase. 1here ls a problem:
alk phos ls ln oLher Lhlngs oLher Lhan Lhe llver ln bone (osLeoplasLlc acLlvlLy), placenLa. So,
how wlll you know wh
oLher Lhlngs)? Look aL gamma g|utamy| transferase b]c |ts spec|f|c for the ||ver (so, lf alk
phos up, look aL gamma gluLamyl Lransferase!). If the gamma g|utamy| transferase IS
e|evated a|ong w|th a|k phos, th|s |s 8ILL DUC1 C8S1kUC1ICN.

A|bum|n prot|me = marker of sever|ty of ||ver damage. lL ls made ln Lhe llver, Lherefore lf
you have severe llver dz (le clrrhosls), lL wlll be decreased. Lven beLLer Lhan LhaL ls
proLhrombln Llme b/c coagulaLlon facLors are made Lhere (mosL are made Lhere vWl ls
noL, however). So, lf you have llver damage, Lhe producLlon of coagulaLlon facLors wlll be
decreased, and 1 wlll be prolonged (lncreased). So, a|bum|n |eve|s and 1 are the 2 best
tests for ||ver sever|ty (1 |s a ||tt|e better than a|bum|n).

1here ls only one auLoAb LhaL ls lmporLanL: ant| m|to Abs |n pr|mary b|||ary c|rrhos|s.

1umor markers: a|pha feto prote|n |s a marker for hepatoce||u|ar carc|noma. Can also use
a|pha-1 ant|tryps|n b/c lL ls made ln Lhe llver (lL ls |ncreased ln hepaLocellular carclnoma).

lf you have fracLlonaLlon of blllrubln (less Lhan 20, 20-30, and 30+ ), can sLarL d/d, Lhen
glve Lransamlnase levels see how lL correlaLes wlLh llver dz: Lransamlnases correlaLe wlLh
vlral hep and con[ blllrubln of 20-30, or obsLrucLlve llver dz (alk phos, gamma gluL) and con[
blllrubln over 30.

IV. V|ra| nepat|t|s

A. MC on hepat|t|s:
MC hep = A (followed by 8, C, u, L ln LhaL order)
A and L = fecal oral, all Lhe oLhers are LransmlLLed parenLally
Pep A = no chronlc carrler sLaLe
216

Pep L = produces a chronlc carrler sLaLe only lf you are pregnanL, leadlng Lo chronlc llver
dz
Pep u = 8equlres Pep 8 Lo lnfecLlon
Pep A = uaycare cenLers (Lherefore should geL vacclne Lo prevenL, ouLbreaks can occur
ln daycare cenLers)
Pep A = !all
Pep 8 = lvuA
Pep C = osL Lransfuslon PepaLlLls
Pep 8 = MC lnfecLlon by accldenLal needle sLlck
8. Sero|ogy:
nAV A lM A A lC
nCV: a C lC A nC1
A
nDV: (same as PCv) u lC A
are anLl-u lgC poslLlve lL means you have Lhe acLlve dz now

So, on A PAv P8v A PLv.

nep 8 (n8V)
I|rst marker that comes up |s surface Ag (n8sAg). lL comes up abouL 1 monLh afLer
? 1
enzyme sLudles are normal. 1he nexL Lhlng LhaL comes up ls Lhe bad guys: L Ag
(n8eAg) and n8V DNA, b]c these are on|y ones that are |nfect|ve. 1hen Lhe flrsL Ab
comes up a lll afLer Lhe unA and L Ag, whlch ls core Ab IgM (Ant|-n8c) (Lhls ls
expecLed b/c Lhe flrsL Ab agalnsL acuLe lnflammaLlon ls lgM). 1he ma[orlLy of people
wlLh Pep 8 recover (abouL 90), Lhose wlLh Plv+ never recover and wlll have chronlc
cases b/c Lhey have no lmmune response Lo knock lL off. lf you do recover Lhe f|rst
th|ngs to go away are L Ag (n8eAg) and n8V DNA. 1he >o08?08
away |s surface Ag (n8sAg). So, surface Ag ls Lhe flrsL Lo come and Lhe lasL Lo leave
look aL Lhe charL and wlll see LhaL S Ag ls Lhe blg
house and L Ag and P8v unA are Lhe lll houses under blg house). ln oLher words, lL
ls lMCSSl8LL Lo be L Ag poslLlve and S Ag negaLlve (L Ag and DNA come up after S
Ag and |eave before).

Surface Ab S Ag ls gone, so Lhere ls Lhls
wlLh noLhlng elevaLed (only has one Ab Lhere, S Ag, L Ag,
P8v unA are all gone, and S Ab noL Lhere yeL). So, how do you know Lhe pL PAu Pep
8 C lM lL sLays Lhere and becomes lgC over Llme. So, Lhe
marker for LhaL w|ndow per|od when a A
arrlved yeL, ls core Ab IgM (whlch Lells you LhaL you PAu Pep 8 and are ln Lhe
217

process of recovery). 1here ls no way you are lnfecLed durlng Lhls perlod why? 8/c
L Ag and P8v unA are noL Lhere. 1herefore, you are noL lnfecLlve lL [usL means
LhaL you PAu Pep 8 and are ln Lhe process of recoverlng. CU AkL NC1 INILC1IVL
Lhls ls beLween Lhe 3
Lh
and 6
Lh
monLh.

S P 8 A core Ab IgG and surface
Ab IgG.

lf you have been vacc|nated, cannoL have anyLhlng b/c you had yeasL make surface
Ag, whlch ls whaL Lhe vacclne conslsLs of. 1he only bad Ab you can geL from ln[ecLlng
A A S A
Surface Ab. nC1 core Ab lgC b/c were noL ln[ecLed wlLh LhaL. Core Ab ls noL a
proLecLlve Ab.
C. Chron|c hepat|t|s now |ong have you had o8+aou?\0&
6 months, you have chronlc Pep 8. So, are you lnfecLlve or noL? are you an lnfecLlve
carrler or healLhy carrler? ?ou auLomaLlcally know lf you are an |nfect|ve chron|c carr|er
|f you have n8V DNA. 1hls means LhaL you are a paLlenL wlLh chronlc Pep 8 LhaL ls
S s need Lo be
lv lvuA If
you are negat|ve for L Ag and n8V DNA but are surface Ag pos|t|ve, then |t makes you
,q>q6- (Lhls does noL mean you are healLhy you are sLlll a chronlc carrler
of Pep 8). lf you are a healLhy carrler, however, Lhe chances of recovery are excellenL
b/c ln abouL one year, S Ag wlll dlsappear and S Ab wlll come up. Wlll also have core Ab
lgC aL Lhls Llme Lhls means LhaL you have a good chance of LoLal recovery. Also have a
good chance of recovery w|th L Ag b]c pt |s a cand|date for A|pha IIN therapy (DCC).
Never g|ve cort|costero|ds to any chron|c v|ra| |nfect|ons.

D. kev|ew:
WhaL we expecL ln acuLe hepaLlLls 8 (whaL would Lhe markers be)? S Ag, L Ag, P8v
unA, and core lgM
WhaL lf Lhe pL ls ln Lhe wlndow perlod? Core lgM
WhaL lf had Pep 8, buL have recovered from lL? Core Ab lgC and surface Ab lgC
WhaL lf pL was vacclnaLed (whaL ls Lhe CnL? Lhlng you should have)? Surface Ab lgC
WhaL lf you have aL Lhe end of 6 monLhs S Ag, core lgM, wlLh everyLhlng else neg?
PealLhy carrler
WhaL lf you have afLer 6 monLhs surface Ag, L Ag, P8v unA and core Ab lgM? lnfecLlve
carrler.

V. Inf|ammatory L|ver D|sorders

218

A. Ameb|as|s: Lntamoeba h|sto|yt|ca
Crganlsm ls reslsLanL Lo acld swallow lL and wlll noL dle ln presence of acld. lL ex-cysLs
ln Lhe cecum, wlLhln an alkallne envlronmenL. Pas a chemlcal LhaL can drlll a hole
Lhrough Lhe mucosa, leadlng Lo flask shaped ulcers, and leads Lo b|oody d|arrhea.
unforLunaLely, b/c Lhe cecum ls dralned by Lhe porLal veln, and ls formlng an ulcer,
Lhere ls a chance LhaL lL can drlll and hole, geL lnLo Lhe porLal veln LrlbuLary and geL Lo
Lhe rlghL lobe of Lhe llver, where lL wlll produce an abscess. lL wlll sLarL dlssolvlng Lhe
llver hence Lerm anchovy pasLe abscess b/c lL looks llke anchovy pasLe (a brownlsh
llquld). lf lL wanLs Lo, lL can drlll a hole Lhrough Lhe rlghL dlaphragm, go Lo Lhe lungs, and
produce an effuslon, and go anywhere lL wanLs ln Lhe sysLemlc clrculaLlon braln. 8x
meLronldazole. 1rophozo|tes 88C 1
only proLozoa LhaL can phagocyLose ls Lntamoeba h|sto|yt|ca (no other amoeba can
qvqS ) Lhls ls a very characLerlsLlc flndlng. MeLronldazole ls used ln Lhe
LreaLmenL of glardlasls, LnLamoeba hlsLolyLlca, vaglnosls, c dlff, and Lrlchlnosls.
8. nydat|d dz

1. ueflnlLlve vs. lnLermedlaLe hosL
Def|n|t|ve host = sexually acLlve worms LhaL have Lhe ablllLy Lo maLe and lay eggs.
Intermed|ate host = only have Lhe larval form, do noL have sexually acLlve adulLs.
1hese are Lhe sLages: AdulL, egg, larva. AdulL lays eggs, and Lhe eggs develop lnLo
l he end sLage
l
anywhere else. lf you have Lhe adulL form ln you, lL wlll glve an egg, whlch changes
Lo larva. Larva form cannoL go anywhere lL ls Lhe end sLage form.

SqqSv->-->->-D
1he sheep dog eaLs some sheep meaL (Lhere are larval forms ln Lhe sheep, Lherefore,
Lhe sheep ls Lhe lnLermedlaLe hosL). uog eaLs sheep, and has larva ln Lhe dog. 1he larva
form develops lnLo an adulL wlLhln Lhe dog, and Lhe dog becomes Lhe deflnlLlve hosL.
1he dog has sexually acLlve worms lnslde lL and Lhe worms lay eggs wlLhln Lhe dog. uog
ls peLLed, geLs eggs on Lhelr hand and lnLo pLs food, whlch ls eaLen. So, now, Lhe pL has
Lhe egg, whlch develops ln Lhe larva (cannoL go any farLher b/c larval form ls end sLage),
and Lhe pL (human) becomes Lhe lnLermedlaLe hosL. So, Lhe sheep ls an lnLermedlaLe
hosL, Lhe dog ls Lhe deflnlLlve hosL and Lhe sheep herder ls an lnLermedlaLe hosL. uo noL
wanL Lo rupLure Lhese cysLs, b/c lf Lhe fluld geLs lnLo Lhe abdomlnal cavlLy, leads Lo
anaphylacLlc shock.

C. 1. so||um (p|g tapeworm)

219

?ou go Lo a barbecue and eaL undercooked pork (larva ln Lhe plg meaL, whlch ls eaLen).
1he larva develop lnLo Lhe adulL form wlLhln Lhe pL (so, Lhere ls a sexually acLlve worm
lnslde). So, pL becomes deflnlLlve hosL, whlle Lhe plg was Lhe lnLermedlaLe hosL. now
you have a famlly member LhaL ls a deflnlLlve hosL (has sexually acLlve worms lnslde
Lhem) leLs say Lhls
hands, so some of Lhe eggs goL lnLo Lhe salad. 1he pL eaLs Lhe salad wlLh Lhe eggs ln lL.
WhaL ls Lhe egg golng Lo form lnslde me? Larva. WhaL ls Lhls called cysLocercl. uo Lhey
form adulLs? no, sLops Lhere. 1herefore, pL has cysLocercosls. WhaL are Lhe |arvae
go|ng to do? 1hey ||ke the eye and the bra|n (where they form a cyst |n the bra|n,
>-k>---kqkqS>-k . So, ln Lhls dz, Lhe pL can
have Lwo forms of lL. lf pL aLe Lhe lnfecLed plg, Lhey can be Lhe deflnlLlve hosL. lf you
geL Lhe egg ln your mouLh, you become an lnLermedlaLe hosL, and Lhe egg can become
larva, whlch wlll go on Lo cysLocercosls. So Lhe larvae form ls Lhe dangerous form ln 1.
sollum.

(MC S/L of caLaracLs = glucocorLlcolds)
VI. Nutmeg L|ver

MCC = 8Pl
1hrombus ln porLal veln wlll nC1 lead Lo nuLmeg llver because porLal veln ls before
empLylng lnLo Lhe llver. Would you have asclLes? ?es. orLal P1n? ?es. varlces? ?es.
8uL ls llver blg and congesLed? no.
1hrombus ln hepaLlc veln: ls called 8udd Chlarl syndrome (MCC polycyLhemla 8ublvera, 2
nd

MCC = blrLh conLrol pllls). Would you have a nuLmeg llver? ?es hepaLlc veln empLles
Lhe llver. ?ou geL a huge llver, and ls a surglcal emergency and dle 100 of Lhe Llme lf

So, Lhese are pre/posL hepaLlc Lhromboses (rehepat|c = porta| ve|n, posthepat|c = hepat|c
ve|n).

VII. A|coho||c ||ver dz

MC man|festat|on |s fatty change (steatos|s). 8/c alcohol nAuP
aceLaLe, and aceLyl CoA. nAuP
fasLlng hypoglycemla, and meLabollc acldosls A CA lA
phosphaLe and 1C and faLLy change, or can be converLed lnLo keLone bodles, whlch causes
an lncreased anlon gap: meLabollc acldosls. laLLy change ls reverslble lf Lhe alcohollc sLops
drlnklng.

A|coho||c hepat|t|s ls very bad, can have hepaLlc encephalopaLhy, asclLes, eLc. Alcohollc
hep ls dlff from faLLy change b/c Lhere ls fever, neuLrophlllc leukocyLosls, very hlgh
220

AS1>AL1, and gamma gluLamyl Lransferase ls up ?
drlnklng you wlll dle. lL ls very serlous sysLemlc dz. lf pL hosplLallzed for alcohollc hep, ls
released and Lakes alcohol, Lhey wlll dle. See Ma||ory bod|es (ublqulnaLed keraLln
mlcrofllamenLs). 1oxlc compound LhaL causes clrrhosls ls aceLaldehyde bound Lo a proLeln,
noL aceLaldehyde by lLself. lLo cell normally ls Lhe cell LhaL sLores vlL A. ln an alcohollc Lhe
aceLaldehyde proLeln complex sLlmulaLes Lhe lLo cell Lo make flbrous Llssue and collagen.
1he lLo cell, whlch ls responslble for sLorlng vlL A, ls now puLLlng down collagen Llssue and ls
responslble for causlng flbrosls. llbrous Llssue ls a blg parL of alcohollc Llssue dz.

VIII. Cho|estas|s

Cho|estas|s = obsLrucLlon Lo blle flow, due Lo a sLone ln Lhe C8u. Lx: have a cholesLerol
sLone wlLh a deep green colored llver. 8lle ls blocked, whlch has con[ blllrubln ln lL and ls
backed up lnLo Lhe llver. 1he con[ blllrubln wlll evenLually reflux lnLo Lhe slnusolds, and
leads Lo blllrubln ln Lhe urlne and llghL color sLools, wlLh nC uroblllnogen ln Lhe urlne. 1he
yellow urlne ls due Lo waLer soluble con[ blllrubln ln Lhe urlne. WhaL enzymes are
elevaLed? Alk phos and gamma gluLamyl Lransferase. WhaL ls Lhe mech for geLLlng rld of
cholesLerol? 8lle. So, you reflux cholesLerol, blllrubln and blle salLs (Lhey are all recycled).
Would lL surprlse you LhaL Lhey have hypercholesLerolemla, Loo? no b/c lL ls recycled. 1he
blle salLs deposlL ln Lhe skln, leadlng Lo lLchlng.
221

2 other causes of cho|estas|s:
8lle ducL radlcal, surrounded by flbrous Llssue, bloody dlarrhea wlLh LLC crampy paln,
[aundlce whaL ls Lhe l8uz? UC
Common blle ducL surrounded by flbrous Llssue dx? r|mary sc|eros|ng cho|ang|t|s.
MCC prlmary scleroslng cholanglLls = UC
WhaL cancer can develop b/c lL lnvolves Lhe blle ducL? Cho|ang|ocarc|noma (MCC ln Lhls
counLry, ln 3
rd
world counLrles, lL ls due Lo Clonorchls slnensls Chlnese llver fluke).

Ik. r|mary 8|||ary c|rrhos|s
30 y/o woman wlLh generallzed lLchlng, flnd enlarged llver on L, normal blllrubln (no
[aundlce), alk phos and gamma gluLamyl Lransferase are huge (obsLrucLlve Lype of
enzymes), Lransamlnases are elevaLed dx? rlmary blllary clrrhosls, whlch ls an
auto|mmune dz that |eads to granu|omatous destruct|on of the b||e ducts |n the porta|
tr|ad L
knock off 230,000 of Lhem. SLlll have 73 LhaL can handle Lhe blllrubln load. 3 years laLer,
only have 30 (300,000 desLroyed). SLlll no [aundlce, evenLually, more knocked off and geL
S
reserve LhaL can handle Lhe blllrubln. 1herefore, Lhere ls no reason Lo have [aundlce early
and lL comes laLe. WhaL ls Lhe Ab Lo order ln Lhls pL? Ant|-m|tochondr|a| ant|bod|es


k. Drug effects
8lrLh conLrol (CC) and anabollc sLerold have Lhe same effecL on Lhe llver. 1he CC and
anabo||c stero|ds both produce |ntrahepat|c cho|estas|s L
sLerolds) develops [aundlce, and vlral serology ls negaLlve, hlgh alk phos and gamma
gluLamyl = due Lo sLerolds (noL hepaL C MCC
lnLrahepaLlc cholesLasls. 1hls ls b/c of Lhe esLrogen durlng pregnancy, whlch produces
lnLrahepaLlc cholesLasls. 8x? uellver baby (goes away afLer dellverlng baby). LeLs say
woman Lakes CC and geLs [aundlce, when she become pregnanL, she wlll develop
[aundlce, Loo b/c of Lhe esLrogen effecL. So, lnLrahepaLlc cholesLasls ls a normal
CC 8oth of these drugs a|so pred|spose to a b9
||ver tumor, ca||ed ||ver ce|| adenoma aka hepat|c adenoma. lL has a nasLy hablL |t ||kes
to rupture, |ead|ng to |ntraper|tonea| hemorrhage (wh|ch can k||| you). Lxample: wL llfLer

collapses. llnd abnormal llver/cavlLy whaL ls mosL llkely cause? 8upLured llver cell
adenoma b/c pL ls on anabollc sLerolds. L/ v4?&&>uu0 u\u>
effects: both can produce b9 |ntrahepat|c cho|estas|s (wh|ch goes away |f you stop the
drug) and ||ver ce|| adenoma wh|ch |s suscept|b|e to rupture. lor women, lf Lhey are on
blrLh conLrol, Lhen geL off lL Lo geL pregnanL
dld noL know abouL (LhaL developed wlLh CC use), Lhen geL pregnanL, Lhen geL an
222

lnLraperlLoneal hemorrhage, and Lhen whaL ls d/d? 8upLured ecLoplc pregnancy or rupLure
lnLraperlLoneal hemorrhage. SLep 2: pregnanL women have Lhe Lendency Lo have splenlc
arLery aneurysm = rupLure.
kI. nemochromatos|s

Lxample: hyperp|gmented pt adu|t that |s d|ffuse|y hyperp|gmented and has d|abetes
(type I d|abet|c) = bronze d|abetes = hemochromatos|s = Ie over|oad, auto rec, reabsorb
too much Ie. Pemoslderosls ls acqulred lron overload by belng an alcohollc. lron
supplemenLs are conLralndlcaLed ln Lhe elderly b/c lL wlll creaLe hemoslderosls and have
8
ls LhaL lnsLead of reabsorblng 10-13 of lron from foods, you are absorblng 100 of lron.
1argeL organ ls Lhe llver. Whenever le ls absorbed lnLo cells, lL produces hydroxyl free
S l
radlcals lenLon rxn). lf you are damaglng llver cells, wlll lead Lo flbrosls and clrrhosls.
1hey ALL have c|rrhos|s |n Ie over|oad, e|ther by hemos|deros|s or hemochromatos|s. ln
clrrhosls, you see llver wlLh brownlsh plgmenL, russlan blue sLaln (Lo see le), and a vL8?
PlCP lncldence of hepaLocellular carclnoma. Can also go elsewherepancreasLherefore
can have LxCcrlne and LnuCcrlne dysfuncLlon, leadlng Lo malabsorpLlon. uesLrucLlon of
lsleL cells leads Lo very brlLLle Lype l dlabeLes. Also deposlLs ln skln and lead Lo
hyperplgmenLaLlon (bronze look). 1hls ls a combo of le deposlLlng Lhere and by sLlmulaLlng
melanocyLes, Lherefore Lhere ls le plgmenLaLlon and melanln. Can go lnLo [olnLs and lead
Lo polyarLhrlLls, can go Lo plLulLary, leadlng Lo hypoplLulLarlsm, can go Lo hearL and produce
resLrlcLlve cardlomyopaLhy. Pow you do screen for |ron over|oad? Serum ferr|t|n. Serum
Ie = h|gh. Lxcess Ie stores, therefore decreased syn of transferr|n. 1he 1I8C |s
decreased. sat |s |ncreased, serum ferr|t|n |s |ncreased. kx? h|ebotomy. uo noL use
chelaLlon Lherapy. 1hey purposely make you le def. 1hls dz ls Lhe nexL Lo Lhe mosL
common auLosomal rec dz. nemos|deros|s = ACUIkLD Ie over|oad from a|coho|.

aa7]u>&?

kayser I|e|scher r|ng brown rlng around cornea. WhaL ls degeneraLlon called?
nepato|ent|cu|ar degenerat|on. t w|th abnorma| movement (chorea) d|sorder,
dement|a, and c|rrhos|s. Auto recess|ve. Defect |n r|dd|ng Cu |n b||e, so, the Cu bu||ds up
and accumu|ates |n the ||ver. very Loxlc. So, over a perlod of monLhs Lo years, you go from
chronlc acLlve hepaLlLls Lo clrrhosls. When you geL a LoLal Cu level, whaL does lL lnclude?
lree Cu and blndlng proLeln for Cu. 1he b|nd|ng prote|n |s ca||ed ceru|op|asm|n. So, some
Cu ls aLLached Lo ceruloplasmln. So, Lhe LoLal Cu measured lncludes bound and free. 93
of a normal LoLal Cu level ls relaLed Lo Cu aLLached Lo ceruloplasmln. So, mosL of Lhe LoLal
Cu level ls bound Lo ceruloplasmln, noL Lhe Cu LhaL ls free. So, 9S |n a norma| person the
tota| copper |s Cu that |s bound and |nact|ve to ceru|op|asm|n. So, ls ceruloplasmln a
223

proLeln? ?es. So, wlLh clrrhosls, are you synLheslzlng ceruloplasmln? no. 1herefore, Lhere
ls a decrease of blndlng proLeln for Cu. So, free cu |ncreased. So, the tota| Cu |eve| |s
decreased (b]c |ess ceru|op|asm|n), but the free Cu |s |ncreased (more unbound). 8x?
Cnamlne (Cu blnder). LenLlcular nucleus messed up (caudaLe nucleus ln Pu)
kIII. C|rrhos|s

never focal, always dlffuse. 1he bumps all over lL are called regeneraLlve nodules. know
y ln Lhe Co phase, and someLhlng has Lo
sLlmulaLe lL Lo go lnLo Lhe cell cycle Lo dlvlde. 1he llver has an amazlng regeneraLlve
capaclLy. 8egeneraLlon of llver cells are hepaLocyLes wlLh no Lrlad, no cenLral veln, and no
slnusolds. Iust wa|| to wa|| hepatocytes wh|ch are worth|ess. 8umps are regeneraLlve
nodules, no Lrlad, Lhere are [usL wall Lo wall hepaLocyLes surrounded by flbrous Llssue.
SLarLs off as mlcronodular (less Lhen 3 mm) and ends up macronodular (over 3 mm). So,
have llver, buL cells noL worklng. Pow ls a porLal veln gonna be able Lo empLy lnLo Lhe llver
l porLal P1n.

Comp||cat|ons: lLLlng edema, asclLes, esophageal varlces, and meLabollc probs (cannot
metabo||ze estrogen, leads Lo gynecomasLla). CannoL look aL gynecomasLla, have Lo feel lL.
S|de effects of prob|ems of estrogen metabo||sm: Slde noLe: 1here are 3 Llmes ln a
llfeLlme where males can develop gynecomasLla. 1. newborns males have boobs b/c
esLrogen from mom, newborn glrls wlLh perlods b/c esLrogen from, Lhen drop off, leads
Lo bleedlng. 2. Males also geL boobs ln Leens (puberLy). 3. Males also geL boobs when
Lhey Lurn old b/c LesLosLerone goes down and esLrogen goes down, leadlng Lo
gynecomasLla so, geL boobs (gynecomasLla) Lhree Llmes LhroughouL llfe, and Lhls ls
normal. Lxample: 13 y/o unllaLeral subalveolar mass, whaL ls managemenL? Leave lL
alone. CynecomasLla ls noL always bllaLeral, lL ls usually unllaLeral. Women have dlff
slze breasLs b/c each breasL has dlfferenL suscepLlblllLy Lo esLrogen, progesLerone, and
prolacLln. Men do noL have breasL Llssue, Lherefore more llkely LhaL one wlll enlarge,
Lhe oLher wlll noL.
palm (flbromaLosls lncreased flbrous Llssue around Lhe
Lendon sheaLhs, causlng flngers Lo coll ln, commonly assoc wlLh alcohollcs) Lhese are
all esLrogen abnormallLles.

CompllcaLlon of AsclLes adulL wlLh asclLes sponLaneous perlLonlLls due Lo L coll. Chlld
wlLh nephroLlc syndrome and geL asclLes and sponLaneous perlLonlLls, whaL ls Lhe
organlsm? SLrep pneumonlae. So, adulLs wlLh asclLes and sponLaneous perlLonlLls = L coll,
whlle kld wlLh asclLes and sponLaneous perlLonlLls = SLrep pneumonlae.

kIV. nepatoce||u|ar carc|noma

224

nodularlLy, Cancer ln hep veln LrlbuLary (le). 1hls cancer almosL always develops ln Lhe
background of clrrhosls. lL ls very rare for hepaLocellular carclnoma Lo develop wlLhouL
clrrhosls presenL. Slnce alcohol ls Lhe MCC MCC nC.
)?0>>>u&\qu8\&u0u40\0\uu0uu&7
1hls cancer can produce ecLoplc hormones LC (leads Lo 2
nd
ary polycyLhemla), lnsulln llke
Cl (leads Lo hypoglycemla). 1umor marker: alpha feLo proLeln. Lxample: pL wlLh
underlylng clrrhosls, and ls sLable. 8uL suddenly Lhe pL beglns Lo lose wL and asclLes ls
geLLlng worse. uo a perlLoneal Lap and lL ls hemorrhaglc (do noL assume lL ls LraumaLlc
from Lhe needle, unless Lhey say lL). lf Lhere ls blood ln Lhe acldlc fluld lL ls paLhologlc
bleedlng. So, th|s hx (wt |oss, beg|nn|ng to deter|orate sudden|y, b|ood |n ac|d|c f|u|d).
know |t |s hepatoce||u|ar carc|noma, but w||| ask what test do you do? A|pha feto
prote|n. M
C
lung cancer, so Lhe 2
nd
MCC laLlon wlLh
smoklng.

8emember Lhe 2
nd
mosL common cause: example of a small bowel obsLrucLlon, Lhe MCC ls

lndlrecL lngulnal hernla.




GALL8LADDLk D2


I. Ask about pathogenes|s of stone too much cho|estero| |n b||e or too ||tt|e b||e sa|ts. ?ou
wlll have a supersaLuraLed sLone wlLh cholesLerol wlll geL cho|estero| stone (MC stone). Cr,
Loo llLLle blle salLs, boLh lead Lo sLones. AnyLhlng LhaL causes blle salL def (clrrhosls,
C C

II. |gment stones

?ellow sLones (know Lhey are noL cholesLerol sLones) 23 y/o female, 8uC crampy paln,
fever, polnL Lenderness, neuLrophlllc leukocyLosls, sLones revealed on ulLrasound. C8C
showed a mlld normocyLlc anemla and a correcLed reLlculocyLe cL of 8. Splenomegaly on
L and famlly hx of splenecLomy. Dx? Congen|ta| spherocytos|s, b/c she has been
88C oL of blllrubln lnLo con[ blllrubln and Lherefore has
supersaLuraLed blle wlLh blllrubln, and forms Ca b|||rub|nate stones that are [et b|ack.
Seen wlLh ulLrasound.
225


WhaL ls Lhe screen|ng test of cho|ce for sLones? ulLrasound. Screenlng LesL of cholce for
anyLhlng ln Lhe pancreas = C1 reason why ls b/c bowel overlles pancreas and messes up
ulLrasound, Lherefore noL as senslLlve. Always puL C1 for pancreas, C8 = ulLrasound (can
Lell dlameLer of C8u Lo Lell lf Lhere ls a sLone ln lL).


226

ANCkLAS

I. Cyst|c I|bros|s
CysLlc flbrosls growLh alLeraLlon b/c mucous ln ducLs of Lhe pancreas. See atrophy b/c
block lumen of exocrlne ducLs, and pressure goes back Lo Lhe glands and LhaL pressure
aLrophles Lhe glands, |ead|ng to ma|absorpt|on. Can cysLlc flbrosls also lead Lo dlabeLes?
?es b/c evenLually flbrose off Lhe lsleL cells, leadlng Lo type I d|abetes, Loo.

Mo|ecu|ar b|o
phenylalanlne. So, you are def of pheny|a|an|ne |n the cyst|c f|bros|s transmembrane
regu|ator prote|n (CI1k). So, all lLs mlsslng ls phenylalanlne. MosL Lhlngs, afLer Lhey are
made ln Lhe rlbosome ln Lhe 8L8, have posLLranslaLlonal modlflcaLlons ln Lhe Colgl
apparaLus, whlch ls where Lhe real defecL ls. 1he rea| prob|em |s when |t gets to the Go|g|
apparatus -S -k- q>>kI N
be|ng degraded |n the ce||, and you end up hav|ng the CI1k. So, Lhe prob ls ln Lhe Colgl
apparaLus lL screws lL up, and never makes lL Lo Lhe surface, Lherefore has no funcLlon.

So, whaL does lL do? In the sweat g|ands, norma||y, |t wou|d reabsorb Na and C| out of the
sweat g|and. 8]c they are def |n th|s, they are |os|ng sa|t, wh|ch |s the bas|s of the sweat
test. 3 y/o kld, fallure Lo Lhrlve, chronlc dlarrhea, resp lnfecLlon, mom sLaLes LhaL Lhe baby
1 Cl
conslderable salL and become salL depleLed when Lhey are overheaLed. Why are all Lhe
secreLlons so Lhlck ln Lhe lungs, pancreas, and blle ducLs? Cl18 regulaLor whaL does lL do?
ln |ungs, need Lo have salL and secreLlons ln Lhe lumens of Lhe resp LracL Lo keep lL
vlscous (Lo keep lL nlce and loose), lf you are mlsslng Cl18, na ls reabsorbed Cu1 of Lhe
secreLlons ln Lhe alrway (Lherefore a lll dehydraLed). And, chlorlde cannoL be pumped lnLo
Lhe lumen of Lhe alrway so you are Laklng away Lhe 2 lmp lngredlenLs wlLh Lhls pump:
Laklng na ouL and noL puLLlng Cl ln. 1herefore Lhese secreLlons are Lhlck llke concreLe. 1he
same ls Lrue for secreLlons ln Lhe pancreas (na pumped ouL and Cl noL puL ln). MCC death =
pseudomonas aerug|nosa. Iert|||ty: whaL ls chance of male wlLh cysLlc flbrosls havlng
chlldren? 0-3 (mosL are lnferLlle), for females, Lhey can geL pregnanL, buL only have 30
chance of geLLlng pregnanL. 1he problem ls LhaL Lhe cervlcal mucous ls as Lhlck as concreLe
and Lherefore Lhe sperm cannoL peneLraLe, and LhaL ls one of Lhe reasons why Lhey are
lnferLlle

II. Acute pancreat|t|s

MC due Lo alcohol, 2
nd
MCC = sLone caughL ln accessory ducLs of Lhe pancreas. Amylase ls
elevaLed. CharacLerlsLlc paln: Lp|gastr|c pa|n w|th rad|at|on |nto the back
reLroperlLoneal organ).
227


Pave an hx of acuLe pancreaLlLls, afLer 10 days, have a mass ln Lhe abdomen and Lhey ask
whaL do you do? C1 whaL ls lL? ancreat|c pseudocyst - a loL of fluld accumulaLes around
an lnflamed pancreas and forms a false capsule and has a poLenLlal Lo rupLure (noL good Lo
have amylase ln perlLoneal cavlLy).

8uC wlLh dysLrophlc calclflcaLlon (doLs on x-ray), whaL do you Lhlnk lL ls? ancreat|t|s. ls lL
acuLe or chronlc? Chron|c b/c Lhere are so many. ls Lhls pL llkely Lo be an alcohollc? ?es.
WhaL else would you expecL le whlch of Lhe followlng you expecL? SLeaLorrhea (one of
Lhe causes of malabsorpLlon need enzymes), or may say you have blle salL def (no, b/c
pancreas has noLhlng Lo do wlLh blle salLs), hemorrhaglc dlaLhesls (yes, vlL k def relaLed Lo


Carc|noma of the head of the pancreas MCC = smoker, 2
nd
MCC = chron|c pancreat|t|s,
pa|n|ess [aund|ce (ma|n|y con[ugated b|||rub|n), ||ght co|ored stoo|s, pa|pab|e G8
--S-vI C slgn permanenLly lndenLlng Lhe duodenum, do barlum sLudy, also
a slgn of pancreaLlc cancer.

Acute pancreat|t|s w|th |nf|ammat|on. WhaL wlll LhaL do Lo perlsLalsls of LhaL duodenum
nexL Lo lL? Pow does Lhe bowel reacL Lo Lhe presence of lnflammaLlon nexL Lo lL? It stops
per|sta|s|ng (noL Lhrough Lhe enLlre bowel, [usL Lhere). lf Lhls ls Lrue, Lhere would [usL be alr
whaL ls Lhls called? Sent|ne| s|gn (senLlnel ls someone
LhaL ls supposed Lo keep waLch) keep waLch of whaL? lnflammaLlon (so, the sent|ne| s|gn
keeps watch of |nf|ammat|on), Lhe classlc area ls Lhe pancreas. 1hls |s ca||ed |oca||zed
||eus (||eus, by def|n|t|on |s |ack of per|sta|s|s). Whenever the bowe| |acks per|sta|s|s, w|||
see a|r accumu|ate and w||| get d|stens|on. WhaL lf you have a segmenL of bowel LhaL ls
dlsLended ln Lhe 8LC? Pas Lo be lnflammaLlon, Lhe cecum ls ln Lhe 8LC and appendlx could
S




228

CnA1Lk 11: kIDNL

I. Cast
mold of whaLever ls golng on ln Lhe nephron/Lubule. lL ls a proLeln LhaL ls congeallng around
whaLever ls presenL ln Lhe Lubule aL LhaL Llme, Lhere ls a mold made, and ls passed lnLo Lhe
urlne and we can see lL under Lhe mlcroscope. 1h|s |s |mp b]c now we do not have to do a
rena| bx of the rena| tubu|es b]c the cast w||| te|| you what |s go|ng on. Lxample: lf you have
glomerulonephrlLls (lnflammaLlon of Lhe glomerulus), you have damaged Lhe caplllarles and
88C 88C
casL LhaL Lells you Lhere ls a glomerulonephrlLls occurrlng. Lxample: WlLh renal Lubule
necrosls, Lhe Lubules are sloughlng off wlLh coagulaLlon necrosls. 1hls wlll form a casL and ls
called renal Lubular casL, and wlll Lell you Lhere ls renal Lubular necrosls. Lxample:
man/woman wlLh acuLe pyelonephrlLls wlLh neuLrophlls lnvadlng Lhe lnLersLlLlum and Lhe
Lubules, Lhere are casL of neuLrophlls (W8C casLs), Lelllng me Lhere ls lnfecLlon of Lhe kldney.
Lxample: spllllng llpld ln urlne ln nephroLlc syndrome and form casL of faL and a faLLy casL LhaL
you can see and polarlze ln Lhe urlne.

II. Ur|na|ys|s

1he f|rst th|ng that d|sappears |n rena| fa||ure |s the ab|||ty of the k|dney to concentrate
ur|ne. 1hls occurs before Cr/8un Lhlnk abouL lncreaslng, or even havlng renal Lubular
casLs. Lxample: Laklng urlne ln Lhe mornlng and dolng Lhe speclflc gravlLy of Lhe urlne and
seelng whaL lL ls. 8/c, spec|f|c grav|ty can te|| you |f |t |s concentrated or d||ute ur|ne. lf
Lhe speclflc gravlLy ls greaLer Lhan 1.023, Lhls means LhaL Lhe pL ls concenLraLlng urlne and
LhaL Lhe kldneys are A8SCLu1LL? nC8MAL (Lhls ls a CPLA LesL). Lxample l
speclflc gravlLy of urlne overnlghL and lL ls 1.010 Lhls ls very hypoLonlc urlne, and lL means
LhaL Lhe pL could noL concenLraLe, and LhaL Lhe pL ls ln renal fallure. (8un/Cr wlll noL help
deLermlne Lhls). 1he urlne LhaL should be concenLraLed ls from a pL LhaL ls sleeplng
overnlghL.

nya||ne cast cast of a prote|n, most|y b9]harm|ess (all oLher casLs have paLhologlcal
slgnlflcance).

III. Crysta|s:
Ur|c ac|d crysta| looks llke a sLar, pP of Lhe urlne has Lo be acldlc Lo form a urlc acld
crysLal. L wlLh gouL wanL Lo sLop crysLals from formlng, and you know Lhey form ln low
pP, whaL do you wanL Lo do wlLh Lhe urlne? Alkallnlze lL. Pow can you do LhaL? Carbonlc
Anhldrase lnhlblLor (aceLazolamlde). 8y blocklng blcarbonaLe reclamaLlon wlll alkallnlze Lhe
urlne, and prevenL sLones from formlng. So, slmple manlpulaLlon of Lhe pP can prevenL
uraLe nephropaLhy.
229

Ca|c|um Cxa|ate crysta| look llke Lhe back of an envelope, why ls Lhls lmp Lo know?
Lxample: sLreeL person comes ln, sLupurous, has lncreased anlon gap meLabollc acldosls.
uo a urlnalysls, and see bunch of calclum oxalaLe sLones whaL dld he drlnk? LLhylene
glycol. WhaL ls Lhe MC stone we pass? Ca oxa|ate. So lf you have a Ca CxalaLe sLone, you
wlll have crysLals assoclaLed wlLh lL.
norse k|dney [olned aL Lhelr lower poles. Wlll ask whaL ls resLrlcLlng Lhe movemenL of Lhe
kldney? lMA lL Lraps Lhe kldney.

IV. Cyst|c dz of the k|dney

A. Infant||e po|ycyst|c k|dney dz,
whlch ls auLo recesslve, Lherefore lL ls presenL aL blrLh. uo you Lhlnk Lhls baby ls
urlnaLlng? no, Lherefore has ollgohydramnlos (decreased amnloLlc fluld). So, baby ls ln
an amnloLlc sac, wlLh hardly any amnloLlc fluld around lL, and Lherefore have
malformaLlon due Lo pressure. Look aL Lhe nose and ears, Lhls ls ca||ed otters face,
wh|ch |s a s|gn of o||gohydramn|os |n po|ycyst|c k|dney dz: f|attened nose, |ow-set
ears, and recessed ch|n). 1hls ch

Lhem up. 1hese cysLs are also seen ln Lhe pancreas, Lhe llver and [usL lncompaLlble wlLh
llfe.

8. Adu|t po|ycyst|c k|dney d|sease: AkDz

Some auLosomal domlnanL dz show eneLrance have Lhe abnormallLy when Lhey
look for lL on Lhe gene, buL do noL express lL. (so you have Lhe geneLlc abnormallLy,
1 d news Lhe bad news ls LhaL
you can LransmlL lL Lo your chlld, Lherefore lL ls dlfflculL Lo recognlze on Lhe pedlgree.
Lxample of peneLrance: famlllal polyposls = 100 peneLrance lf you have Lhe gene,
you have Lhe dz. Lxample of lncompleLe peneLrance: marfan abnormallLy on

ls lncompleLe peneLrance). Akuz ls anoLher example of lncompleLe peneLrance.

So, Akuz ls an auLosomal domlnanL dz LhaL ls noL presenL aL blrLh b/c Au dz have
de|ayed man|festat|ons. See cysLs by 10-12 years of age, always geL n1N wh|ch w|||
then pred|sposes 2 types of b|eeds: (1) Charcot-8ouchard aneurysms (a blood cloL) and
(2) see blood all over Lhe braln, due Lo subarachnold hemorrhage, Lherefore Lhe blood ls
due Lo rupture berry aneurysm. Subarachno|d hemorrhage


230

MV (m|tra| va|ve pro|apse): Lxample: hx of P1n, abnormallLy of ulLrasound ln Lhe
renal pelvls, and had cllck murmur (Lherefore Mv) dx? Akuz. 1here ls a hlgh assoc
of Mv wlLh Lhls.

D|vert|cu|os|s also has a hlgh lncldence. Lxample: pL wlLh P1n, abnormallLy on
ulLrasound ln renal area, losL 600 mls of blood all of a sudden, leadlng Lo hemaLochezla
(MCC hemaLochezla = dlverLlculosls).

231

V. G|omeru|ar stuff

A. Nomenc|ature of the k|dney dz:
, ---62NNNUk qk-S->v-v>>q--
Lxample: Llpold nephrosls does LhaL have Lype lll? no
Lxample: local segmenLal glomerular sclerosls? no
Lxample: ulabeLlc glomerulosclerosls? no.
Lxample: lgA glomerulonephrlLls, dlffuse membranous glomerulonephrlLls? ?es

W , Lhls means LhaL LvL8? glomerulus has someLhlng wrong wlLh lL
W ? noL all glomerull lnvolved.
WhaL lf dz ls focal and dz ln Lhe glomerulus ls focal? Pave a problem Lhls ls called local
SegmenLal Clomerulus
WhaL does prollferaLlve mean? Pave loLs of Lhem. So, you have many nuclel. lf all Lhe
glomerull have a loL of nuclel, Lhls ls dlffuse prollferaLlve glomerulonephrlLls
lf you [usL see Lhlck membranes, lLs membranous glomerulonephrlLls
lf you see boLh lncreased cell and Lhlckened membrane? MembranoprollferaLlve
glomerulonephrlLls

8. Anatomy]schemat|c

1he order ls: blood, endoLhellal cells of Lhe caplllarles, underneaLh Lhere ls a 8M, and
Lhen Lhe vlsceral eplLhellal cells (looks llke feeL = podocyLes, whlch have spaces ln
W
makes]synthes|zes the G8M? V|scera| ep|the||a| ce||s (podocytes). WhaL keeps
Albumln ouL of Lhe urlne normally? SLrong negaLlve charge of Lhe 8M. Who ls
- 8M A GAG ca||ed heparan su|fate, wh|ch has a strong
neg charge. lf we lmmunologlcally damage Lhe vlsceral eplLhellal cell, whaL do we
1 8M
Lhe urlne, whlch means you poLenLlally can have nephroLlc syndrome lf you splll >3.3
grams ln 24 hrs).

C. 1est on kena| 8x
Sta|ns rouLlne P & L hemoLoxylln sLalns, sllver sLalns. Immunof|uorescent sLaln
paLLern can be llnear or granular (aka lumpy bumpy), whlch are Lhe only 2 paLLerns.
1 A 1
bx, A l lA
lA A lf Lhere are any, lL wlll aLLach Lo lL and
make a fluorescenL Lag. 1here are also Lags for lgC, C3, flbrlnogen so can geL an ldea

232

l
Lhey are Lhere. WhaL Lells us where lmmune deposlLs and lmmune complexes are
locaLed are LM. So, we do sLalns, fluorescence, and LM. Pow can we Lell LhaL Lhe
podocyLes are fused? Can only Lell by LM b/c lLs so small.
VI. D|fference between Ab recogn|t|on vs. |mmune comp|exes

ueLecL wlLh Ab whlch have 2 Ag recognlLlon slLes on Lhe Ab. Goodpasture syndrome |s an
NvL-uSI So, Lhey geL ln Lhe blood Lhey geL lnLo Lhe glomerular caplllary and are
dlrecLed agalnsL Lhe 8M. Wherever Lhere was a spoL on Lhe 8M you wlll see an lgC Ab.
1 8M wlLhouL lgC. So, whaL lf we do a fluorescenL Lag for
lgC overlylng Lhe glomerulus W 8M
Lhe enLlre glomerulus. lL ls llnear.
MCC ||near pattern on |mmunuf|uorescence = Goodpastures.

Immune comp|exes Ag wlLh Ab aLLached and ls clrculaLlng ln Lhe bloodsLream, hence Ag-
Ab comp|ex le |upus = |mmune comp|ex dz: Ag = DNA, Ab = ant|-DNA Lhey aLLach Lo
e/o and floaL around and deposlL ln cerLaln places, ln Lhls case lL wlll deposlL ln Lhe
glomerular caplllary, type III n (b]c |mmune comp|ex). 8/c Lhey are lmmune complexes,
A A A Lherefore
Lhey are blgger, have dlff solublllLles, have dlff charges neaL ln Lhe
glomerulus. So, dependlng on Lhe slze and charge wlll depend on where Lhey locaLe
Lhemselves. le lf Loo blg, wlll locaLe under Lhe endoLhellal nucleus. So, Lhls would be called
a subendoLhellal membrane Lhey are so blg LhaL Lhey flL under a podocyLe (Lhey cannoL
geL Lhrough Lhe 8M). Lupus ls llke Lhls, Loo Lhey cannoL geL passed Lhe 8M and hangouL
under Lhe endoLhellal cells. ost strep GM bacter|a| Ag w|th Ab aga|nst (|mmune
comp|ex), wh|ch |s very sma||, and very so|ub|e. 1hey can go a|| the way past the 8M and
depos|t under the ep|the||a| s|de th|s |s a subep|the||a| depos|t. So, how do you flnd ouL
where Lhe deposlLs are? CannoL see wlLh lmmunufluorescence, buL wlll be able Lo see wlLh
LM b/c Lhey are elecLron dense (meanlng LhaL Lhey lncrease Lhe denslLy wherever Lhey
are). So, lmmune complexes have dlff solublllLles, dlff charges, and randomly go
underneaLh Lhe endoLhellum, under Lhe subeplLhellal surface, Lhey wlll noL have a nlce
smooLh llnear paLLern llke anLl basemenL memb A Lxample: 0u&?>u&
|ts not Goodpastures) |t cou|d be any |mmune comp|ex dz |upus, post strep, IgA
g|omeru|onephr|t|s. Can geL a hlnL of whaL Lhe dz ls, dependlng on whaL ls ln Lhere le
whaL ls Lhe on|y g|omeru|ar nephr|t|s that you can on|y dx w|th |mmunuf|uorescence? IgA
g|omeru|onephr|t|s. 8/c lf you are gonna call lL glomerular nephrlLls, Lhls means LhaL Lhere
ls no lgC ln Lhere, buL lgA. So, Lhe only way Lo accuraLely dx lgA glomerulonephrlLls ls Lo
prove LhaL lL ls lgA and noLhlng else. Granu|ar]|umpy bumpy pattern when you see th|s,
q -DN> NNN] -uS -uS
aga|nst the 8M |s not a type III, but a type II. Whereas, |mmune comp|exes are type III.
233

VII. Nephr|t|c vs. Nephrot|c G|omeru|onephr|t|s
1here are 2 types of g|omeru|onephr|t|s: nephr|t|c or nephrot|c (cannoL be boLh aL same
Llme, however, lL can sLarL ouL nephrlLlc and become nephroLlc)

A. Nephr|t|c Syndrome:

nas un|que cast LhaL ls red, and looks llke blconcave dlsk k8C casts (unlque Lo

grams ln a 24 hr perlod (b/c lf lL dld, lL would be nephroLlc) so lL ls mlld Lo moderaLe
proLelnurla. ?ou are spllllng proLeln, buL noL Lo Lhe same level as nephroLlc, Lherefore
w||| not have plLLlng edema, asclLes l
ollgurla? ?es all Lhe glomerular caplllarles have swollen up, Cl8 would decrease, and
Lhls would lead Lo ollgurla. Are you decreaslng Lhe absorpLlon or noL fllLerlng na? yes.
So does Lhe na bulld up? ?es Lherefore run Lhe rlsk of P1n. So, c|ass|ca||y what you
- q-- S - q-k qS k >-v-k U7fk ->#
prote|nur|a (th|s |s the def|n|t|on)

8. Nephrot|c Syndrome:

Pas a dlfferenL casL (fatty cast), have greater than 3.S grams of prote|n |n a 24 hr ur|ne
samp|e. W||| a|so have p|tt|ng edema.

So, lf you sLarLed ouL nephrlLlc (88C casLs, mlld/moderaLe proLelnurla) and all of a sudden
you sLarL seelng plLLlng edema, sLarL seelng over 3.3 grams of proLeln ln Lhe urlne over 24
hrs, and faLLy casLs Lhen nephrlLlc has become nephroLlc.

VIII. Nephr|t|c Syndromes

A. ro||ferat|ve G|omeru|onephr|t|s
All Lhe glomerull are dlffuse, Loo many nuclel

8. ost strep GN

Lxample: scarleL fever 2 weeks ago, presenLs wlLh hemaLurla, 88C casLs, mlld Lo
moderaLe proLelnurla, P, perlorblLal pufflness. LM: lumen of caplllary, bump on lumen
ls endoLhellal cell, underneaLh ls 8M (graylsh), and eplLhellal cells under. Pas boulders
LhaL are denser Lhan Lhe normal glomerular 8M Lhese are lmmune complexes. ln Lhls
case, lL Lhe bacLerla ls Lhe Ag-Ab lmmune complexes. Whlch slde are Lhey closer Lo?
Closer Lo eplLhellal slde, Lherefore Lhey are subeplLhellal deposlLs hence posL sLrep
CMn.
234


C. Lupus GN

Lxample AnA
unA A Lupus a|most a|ways |nvo|ves the k|dney. 1here are 6 Lypes, and
Lhe |mportant one to know |s type IV, whlch ls a d|ffuse pro||ferat|ve
g|omeru|onephr|t|s, whlch ls Lhe MC overall one seen ln Lupus. Pas many nuclel,
Lherefore prollferaLlve, has wlre loops. (orlenL Lo LM) deposlLs ln 8M are anLl unA
deposlLs. Would you agree LhaL Lhey are ln Lhe endoLhellal cell? ?es. So whaL ls Lhls
locaLlon? SubendoLhellal deposlLs. odocyLes wlLh sllL pores ln bLwn are noL fused b/c lf
Lhey were, lL would be nephroLlc syndrome. Also see lumen, endoLhellal cells and
deposlLs. lmmune complexes a 8M

D. Crescent|c GN

Clomerulus surrounded by prollferaLlng cells LhaL are parleLal cells b/c noL ln Lhe
glomerulus, and has crescenL shape, hence Lhe name crescenLlc glomerular nephrlLls.
1hls ls Lhe WCkS1 g|omeru|ar nephr|t|s to have b]c |n 3 months, pts w||| go |nto acute
rena| fa||ure and d|e un|ess pt |s on d|a|ys|s M
glomerulonephrlLls, buL Lhe only one l need Lo know ls Goodpastures, th|s |s a
NLnkI1IC dz, th|s dz has crescent|c g|omeru|onephr|t|s on bx (therefore a 8AD dx).

Ik. Nephrot|c Syndromes:

L wlLh casLs (faLLy casLs), polarlzed speclmen wlLh malLese cross Lhls ls cholesLerol ln Lhe
urlne. When cholesLerol ls polarlzed, lL looks llke a malLese cross. 1hese fatty casts are
pathonognom|c for nephrot|c syndrome. CreaLer Lhan 3. 3 grams proLeln for 24 hrs, faLLy
casLs ln Lhe urlne, asclLes, plLLlng edema, rlsk of sponLaneous perlLonlLls lf you are a chlld.
Crganlsm? SLrep pneumonla ln klds, L coll ln adulLs.

A. L|po|d nephros|s aka M|n|ma| Change Dz:
Lxample: LM of 8 y/o boy LhaL had an u8l one week ago, and now ls all swollen, has
plLLlng edema LhroughouL body (anasarca) and asclLes, normo-Lenslve, no P1n, saw
noLhlng on renal bx, buL Lhen dld a LM see 88C ln glomerular caplllary lumen. So, see
endoLhellal cells, see 8M (wlLhouL elecLron dense deposlLs), podocyLes (fused) fus|on
of podocytes |s ALWAS seen |n any cause of nephrot|c syndrome. MalLese crosses ln
urlne. ux? L|po|d nephros|s. All pL wlLh nephroLlc syndrome have hypercholesLeremla.
Slnce Lhey have glomerular dz and some of Lhe cholesLerol can geL lnLo Lhe urlne, some
can form casLs ln Lhe urlne. Aka mlnlmal change dz. Why ls Lhls happenlng? Pas losL
neg charge ln C8M, Lherefore albumln can geL Lhrough. 1hese pLs have a selecL
235

proLelnurla
grams per 24 hrs. 8x corLlcosLerolds (usually goes away ln 1 year never Lo come back
agaln). 1he MCC nephrot|c syndrome |n k|ds.
8. Ioca| Segmenta| G|omeru|osc|eros|s

Lxample: 0u1a<Lw/ plLLlng edema Lherefore look aL urlne and noLe LhaL ls
greaLer Lhan 3.3 grams over 24 hrs. Pas faLLy casLs ln urlne and has P1n. uo bx, and
already know whaL you are gonna see b/c lL Lhe MCC nephrot|c syndrome |n AIDs pt.
Cn bx, some of Lhe glomerull are abnormal and oLhers are normal, buL only a parL of Lhe
glomerulus ls messed up. 1herefore, lL ls focal segmenLal. 8/c Lhe renal bx wlLh LM and
lmmunofluorence dld nC1 show deposlLs, S
called focal segmenLal glomerulosclerosls. 1hls ls 0)>u&u&a&a<? .
nexL Lo rapldly progresslve crecenLrlc glomerulonephrlLls, Lhls ls Lhe nexL worse
glomerular dz.

C. D|ffuse membranous g|omeru|onephr|t|s

Lxample: adulL wlLh plLLlng edema, over 3.3 gram per 24 yrs, faLLy casLs. uo a bx and
see . Powever Lhe 8M ls Lhlcker. ux?
D|ffuse membranous g|omeru|onephr|t|s = MCC nephrot|c syndrome |n adu|ts. 1hls ls
subeplLhellal deposlL. Lp|membranous sp|kes sp|ke ||ke |es|on on the outs|de of G8M
seen w|th s||ver sta|n = dlffuse membranous glomerulonephrlLls (only one LhaL looks
llke LhaL).

Many Lhlngs can cause Lhls (drugs, cancer, noLhlng, lnfecLlons), some Lhe drugs lnclude
nSAlus, Pep 8, capLoprll (klng of LreaLmenL of dlabeLlc nephropaLhy and hearL fallure),
malarla, syphllls, colon cancer (lmmune complex ls anLl-CLA A L
renal fallure and can dle unless you geL a renal LransplanL

D. 1ype I and II Membranopro||ferat|ve G|omeru|onephr|t|s
-, ---6qk--NNNUk |mmune comp|ex!)

1. 1ype l has a relaLlonshlp wlLh Pep C how do you remember? Membranous = Pep 8
(also remember Lhe vascullLls olyarLerlLls nodosa), MembranoprollferaLlve = Pep
C (also remember cryogloblnemla).
So, type I |s a subendothe||a| depos|t that produces nephrot|c syndrome.

2. 1ype ll ls less common, and has an AuLo Ab agalnsL C3, called C3 nephrlLlc facLor. lL
causes C3 converLase Lo become overacLlve and ls consLanLly breaklng complemenL
236

down. So, Lhe lowesL complemenL levels you wlll see ls ln Lype ll glomerular
nephrlLls Lhls ls called dense deposlL dz b/c Lhe enLlre 8M an lmmune complex.

tram tracks mesanglal cell (sLrucLural componenL of Lhe glomerular caplllary) Lhe
mesanglal cell ls exLendlng lLself beLween Lhe 8M and Lhe endoLhellal cell, maklng lL
8M
Lram Lrack MembranoprollferaLlve dz
L. D|abet|c G|omeru|osc|eros|s

Classlc slgn: blg round balls on P and L sLaln. When Lhere ls excess red ln Lhe cell, Lhlnk
hya||ne arter|o|osc|eros|s, Lhls ls a small vessel dz of dlabeLes and P1n. 1he very flrsL
vessel L L S
lumen ls narrow ln Lhe efferenL arLerlole, Lhe Cl8 wlll lncrease. So, whaL ls Lhe Cr
clearance? lncreased. So, ln early dlabeLlc nephropaLhy, Lhere ls an |ncreased GIk and
Cr c|earance. Why? 8/c Lhe efferenL arLerlole ls hyallnlzed and obsLrucLed. ls Lhls bad?
?es as a resulL Lhe glomerulus wlll Lake a poundlng for Lhe nexL Len years leadlng
ln[ury called hyperfllLraLlon damage. WhaL ls Lhe process where glucose aLLaches Lo an
aa ln a proLeln)? nonenzymaLlc glycosylaLlon. LeLs say Lhls ls also golng on b/c Lhe pL ls
noL waLchlng hlmself Loo well, Lherefore we are nonenzymat|ca||y g|ycosy|at|ng the
G8M. WhaL would happen when you glycosylaLe a 8M whaL ls lL permeable Lo?
roLeln. So, have all Lhls pressure on Lhe glomerular caplllary b/c Lhe efferenL arLerlole
and also nonenzymaLlcally glycosylaLlng Lhe C8M, so lLs permeable Lo proLeln. So, Lons
of proLeln golng lnLo Lhe urlne. When you lnlLlally sLarL seelng lL, ls called
m|croa|bum|nur|a. Wlll Lhe sLandard dlpsLlck for proLeln deLecL LhaL? no. 1here are
speclal dlpsLlcks LhaL are avallable Lo deLecL Lhls called mlcroalbumlnurla dlpsLlcks. So,
mlcroalbumlnurla? nave
to g|ve pt ACL |nh|b|tor b/c you wanL Lo sLop progresslon of Lhls. Pow wlll lL work?
AfferenL arLerlole ls conLrolled by CL2, Lhe efferenL arLerlole ls conLrolled by A1 ll
(whlch consLrlcLs lL). So, when you glve an ACL lnhlblLor, whaL happens Lo A1 ll level? lL
decreases. So, b/c A1 ll decreased, you Lake off Lhe vasoconsLrlcLlve elemenL lL has on
lL. Lven Lhough lL was hyallnlzed, lL wlll open Lhen lumen, Laklng pressure off Lhe
glomerulus, and decrease Lhe fllLraLlon raLe. So, Lhe consLanL poundlng on Lhe
glomerulus ls Laken away. need Lo geL glycosylaLed Pb (PbA1c) under 6, buL Lhe ACL
lnhlblLor canL do lL all, so musL have perfecL glycemlc conLrol, oLherwlse wlll go lnLo
chronlc renal dz. lf Lhey can do Lhls, Lhe ACL |nh|b|tor w||| prevent the dz. 1he ACL
|nh|b|tor a|so he|ps n1N. lnk sLuff ls Lype lv collagen ln Lhe mesanglum. lL bullds up,
ez Lo see blg clrcle (blg balls/golf balls/ChrlsLmas balls) aka klmmelsLlel-Wllson nodules
Lhls ls nodular glomerular sclerosls.

I. Amy|o|d
237

Llke Lo deposlL ln Lhe kldneys. lLs a speclal proLeln. Sta|n w|th Congo red, and after you
po|ar|ze |t, |t has a (granny sm|th) app|e green b|refr|ngence. LlghL green ls whaL Lhe
amylold ls supposed Lo look llke when you polarlze lL wlLh a Congo 8ed sLaln. Amylold
and dlabeLlc glomerular sclerosls are nephroLlc syndromes.

238

G. Summary nephrot|c:
Llpold sclerosls = MCC nephroLlc ln klds
l lvuA Alu
ulffuse Membranous glomerulonephrlLls = MC ln adulLs
1ype l and ll MembranoprollferaLlve glomerulonephrlLls = Lype l wlLh hep C relaLlonshlp,
Lype ll wlLh auLoAb agalnsL C3 (lowesL complemenL levels seen)
ulabeLlc nephropaLhy
Amylold

k. Combo of Nephr|t|c and Nephrot|c Syndrome

A. IgA G|omeru|onephr|t|vS

lgA glomerulonephrlLls ls a vA8lAn1 of Penoch Schonleln purpura b/c lL ls an lmmune
complex dz, anLl lgA Abs (so ls Penoch Schonleln palpable purpura ln buLLocks of legs,
polyarLhrlLls, Cl bleed, hemaLurla (88C casLs))

Cn lmmunofluorence, everyLhlng shows up ln Lhe mesanglum. Lxample: ln k|ds,
presenLs wlLh eplsodes of gross hemaLurla, goes away, comes back a few years laLer, ln
adu|ts, presenLs wlLh eplsodlc bouL of mlcroscoplc hemaLurla. So, have a lll hemaLurla,
goes away, and comes agaln. Lll proLelnurla, no P1n. When lL sLarLs geLLlng worse (10
It |s the MC of a||
g|omeru|onephr|t|s and |s type III n.

kI. 8UN]Cr rerena| Azotem|a

Can separaLe prerenal azoLemla vs. renal fallure
8UN = blood urea nlLrogen and Cr = end producL of creaLlne meLabollsm. urea can be
fllLered and reabsorbed ln Lhe prox Lubule (so lLs noL a perfecL clearance subsLance), Cr
ls only fllLered ln Lhe kldney and ls reabsorbed or secreLed. (lnulln clearance ls beLLer).
If you take the norma| 8UN |eve| (10), and norma| Cr |eve| (1mg]dL), w||| have the
norma| rat|o of 10:1.

When you have prerena| azotem|a, Lhere ls an lncrease ln 8un (Lhls ls whaL azoLemla
means). re = before, Lherefore Lher ln oLher
words, Lhere ls noLhlng wrong wlLh Lhe kldney, buL Lhe CC ls decreased (from any cause
- le CPl, Ml, hypovolemla, cardlomyopaLhy, eLc). Anyth|ng that decreases CC w||| |ead
to prerena| azotem|a b]c the GIk w||| decrease. lf you have less renal blood flow, you
wlll fllLer less and Lhe Cl8 wlll decrease. So, when lL decreases, lL glves Lhe prox Lubule
more Llme Lo reabsorb llLLle blL more urea Lhan normal. So, Lhere ls lncrease prox
239

Lubule reabsorpLlon of urea. WhaL abouL Cr? We know LhaL lL ls noL reabsorbed, buL
you do have Lo geL rld of lL Lhrough Lhe kldneys. So, even Lhough lL ls noL reabsorbed,
Lhe Cl8 ls decreased, Lhere ls a back up of Cr and wlll noL be able Lo clear lL as fasL.
1herefore, Lhere wlll be an lncrease ln serum Cr. 1here ls llLLle more of an lncrease ls
urea b/c lL ls belng reabsorbed Lhan wlLh Cr. So, Lhere ls a dlsproporLlonaLe lncrease of
8un/Cr. All you have Lo remember ls 13:1. So, greater than a 1S:1 8UN]Cr = prerena|
azotem|a.

Lxample: Lhe pL has CPl, 8un ls 80 and Cr ls 2. So, boLh are elevaLed, buL Lhe 8un/Cr
raLlo ls 40:1, lndlcaLlng LhaL lL ls prerenal azoLemla, and Lhe pL does nC1 have A1n.

LeLs say pL Lruly has rena| fa||ure o||gur|a, rena| tubu|ar casts, acute rena| fa||ure. 1hls
w||| affect the 8UN]Cr LUALL b/c someLhlng ls wrong wlLh Lhe kldney, Lherefore Lhe
same effecL on Lhe 8un ls Lhe same on Cr. lor boLh, urea has Lo be fllLered ouL of Lhe
kldney and lL has falled boLh lncreased proporLlonaLe Lo each oLher b/c boLh have Lhe

creaLlnlne, so Lhey lncrease ln proporLlon Lo each oLher b/c Lhe urea ls noL belng
reabsorbed anymore b/c Lhe kldney ls ln shock. Lxample: 8un = 80, Cr = 8, Lherefore Lhe
8un/Cr raLlo ls 10:1, and pL ls ln renal fallure. So, even Lhough Lhe 10:1 ls malnLalned,
sLlll have renal fallure b/c lL has lncreased so much. If the rat|o |s 1S:1, |t |s prerena|
azotem|a, |f |t |s |ncreased and st||| 10:1, |ts rena| fa||ure.

kII. Acute kena| Ia||ure

A. Acute 1ubu|ar Necros|s:
MCC = Ischem|c Acute 1ubu|ar Necros|s Lhls ls whaL you worry abouL Lhe mosL when
Lhe CC decreases, pt deve|ops o||gur|a W CC
azoLemla, you have a decrease ln Cl8, whlch ls anoLher cause of Lhe ollgurla. So,
decrease ln CC and ollgurla ls vL8? 8Au, and sLarL Lo see 8un/Cr go up need Lo know
lf lLs prerenal azoLemla, or renal azoLemla Lo dlsLlngulsh, geL a 8un/Cr. lL lLs 13:1, lLs
sLlll prerenal. 8uL lL can progress Lo renal fallure lschemlc acuLe Lubular necrosls. MCC
|schem|c acute tubu|ar necros|s = not treat|ng prerena| azotem|a. So, |schem|c A1N |s
the worst the get and the 8UN]Cr rat|o w||| be norma|, but |ncreased |n va|ues (|e
80]8)

Coagu|at|on necros|s: Sloughs off, blocks lumen and conLrlbuLes Lo ollgurla, and see
casLs ln Lhe urlne. 1he casLs are renal Lubule casLs. So, combo of rena| tubu|ar casts,
o||gur|a, 8UN]Cr of 10:1 = A1N.

240

Why does Lhls have such a bad prognosls? When pL has lschemlc necrosls, noL only are
you kllllng Lhe Lubular cells, buL Lhe 8M also geLs damaged, so Lhe sLrucLural lnLegrlLy of
Lhe Lubule ls belng Laken away, whlch ls noL good. When you have llver damage, and
damage llver cells, and Lhe cells regeneraLe, Lhe cells are noL regeneraLlng slnusolds and
l 8M
A1n or ls ln Lhe process of dolng LhaL, can you regeneraLe a Lubular cell wlLhouL a 8M?
no. So, Lhe more necrosls, Lhe more 8M are desLroyed, Lhe worse Lhe prognosls b/c
cannoL regeneraLe and cannoL geL back normal funcLlon. 1hls ls why lL ls such a bad dz.
1here are 2 parts of the nephron that are most suscept|b|e to |schem|a what are
they? Stra|ght port|on of the prox tubu|e and th|ck ascend|ng ||mb of the medu||ary
segment (where the Na]k]2 C| co-transport pump |s). 1hese Lwo parLs undergo
coagulaLlon necrosls and sloughlng off. So, wlll see Lhese fall off ln Lhe proxlmal Lubule
and also ln Lhe Lhlck ascendlng llmb of Lhe medullary segmenL.

8. Nephrotox|c A1N:

CenLamycln, AC. lf Lhey are nephroLoxlc, whaL ls Lhe flrsL Lhlng Lhey wlll fllLered from
Lhe glomerulus? roxlmal Lubule. So, nephrotox|c tubu|ar necros|s re|ated to drugs
|nvo|ves the prox|ma| tubu|e. And, Lhe 8M remalns lnLacL, Lherefore Lhe prognosls of
nephroLoxlclLy ls way beLLer for 2 reasons: only affecLlng Lhe proxlmal Lubules and noL
affecLlng Lhe 8M. 1he )&0uuql?
nd
MCC = |ntravenous pye|ograms).
WhaL ls Cl8 ln 80 y/o? lL ls decreased Lhe Cr ls 4 mls/mln, whlch ls normal ln older
people. Cr clearance decreases along wlLh Cl8 as Lhey geL older, so, lf you are glvlng a
drug wlLhouL nephroLoxlclLy Lhe same dose as a young person, you wlll be kllllng Lhe
older person 1 AC MCC A1n
decreaslng Lhe dose of Lhe drug Lo decrease nephroLoxlclLy.

kIV. 1ubu|ar and Interst|t|a| D|sorders of the k|dney

A. Acute ye|onephr|t|s:
Pow do you separaLe lL from a lower u1l? very easlly. yelonephrlLls ls seen more ln
women b/c of Lhelr shorL ureLhra. Acute pye|onephr|t|s |s a system|c |nfect|on and |s
an |nfect|on of the k|dney proper. Pow does lL geL lnLo Lhe kldney? AL Lhe
ureLoveslcular [unc, Lhe muscle squeezes so Lhere ls no reflux of urlne from Lhe bladder
lnLo Lhe ureLer. 1hls ls Lrue ln normal people. Powever, noL all people have a normal
veslcoureLeral [uncLlon. So, whaL happens ln a pL wlLh a bladder lnfecLlon and Lhe
[uncLlon ls lncompeLenL, lL leads Lo ves|coureta| ref|ux, and Lhe lnfecLed urlne refluxes
up lnLo ureLers, and leads Lo ascendlng lnfecLlon LhaL goes all Lhe way up Lo Lhe kldneys.
So, Lhey wlll ask you, L0u0\0o((?xa?+0uu/uu/>uu/
pye|onephr|t|s) due to ascend|ng |nfect|on from the beg|nn|ng of the urethra. Lvery
241

woman (has noLhlng Lo do wlLh cleanllness) has Lhe same L coll seroLype ln her sLool aL
Lhe lnLrouLus of Lhe ureLhra and her vaglna. So, wlLh Lrauma or cerLaln seroLypes of L
coll, lL can ascend up Lhe ureLhra lnLo Lhe bladder. lf Lhe pL has an lncompeLenL
S u1l
beglnnlng of Lhe ureLhra on up.

WlLh acute cho|ecyst|t|s, have pa|nfu| ur|nat|on (dysur|a), |ncreased frequency,
suprapub|c pa|n, NC fever, no f|ank pa|n, NC W8C casts (w|th neutroph||s |n them)
why? 8]c the W8C casts deve|op |n the rena| tubu|es, they do not deve|op |n the
ureter or the b|adder, they deve|op |n the k|dney |n the tubu|e.
So, fever, f|ank pa|n, and W8C casts = ACU1L LLCNLnkI1IS. So, lLs an ascend|ng
|nfect|on due to |ncompetent ves|coureta| [unc. 1hls usually shows up ln newborn glrls
(and wlll be a prob for resL of llves).

Lxample: kldney wlLh whlLe spoLs = abscesses seen ln pyelonephrlLls. lf you have
consLanL acuLe aLLacks of pyelonephrlLls, can become chronlc. 1herefore have lncreased
rlsk of P1n and renal fallure.

8. Chron|c ye|onephr|t|s

Lxample: scarred kldney (on corLex), blunLlng of Lhe calyces (occurs under Lhe scar),
seen on lnLravenous pyelograms dx? CP8CnlC pyelonephrlLls. So, b|unt|ng of the
ca|yces = CnkCNIC pye|onephr|t|s.

C. Acute Drug-|nduced |nterst|t|a| nephr|t|s

Can drugs produce a nephrlLls lnvolvlng Lhe lnLersLlLlum and Lubules? ?es can be acuLe
and chronlc and ez Lo dlagnose. Why? 8/c wlll have fever, and develop a rash. Iever +
kash (obvlously due Lo drug, b/c sLarLed afLer Laklng Lhe drug), o||gur|a, eos|noph|||ur|a
(eos|noph||s |n the ur|ne pathognomon|c). 1hls ls called acute drug |nduced
|nterst|t|a| nephr|t|s. 1hls ls more and more common, and ls a very common cause of
chronlc renal fallure. So, puL pL on drug, geL fever, rash, ollgurla = dlscard/sLop drug
(never glve agaln) Lhls ls a combo of Lype l and lv P?.

Ana|ges|c nephropathy
Lxample: dlscoloraLlon ln renal medulla, pale lnfarcL, renal papllla sloughed off rlnged
slgned, and on pyelograms Lhere wlll be noLhlng Lhere [usL an empLy space. ux?
Ana|ges|c nephropathy. 1hls from combo of acetam|nophen and asp|r|n over a |ong
per|od of t|me. Acetam|nophen ls produclng free radlcals. 8/c of Lhe poor clrculaLlon ln
Lhe medulla, Lhere ls free radlcal damage on Lhe Lubular cells of Lhe medulla. Asp|r|n
242

wlll block CL2 (a vasodllaLor), Lherefore angloLensln ll (a vasoconsLrlcLor) ls ln charge of
Lhe renal blood flow. vasoconsLrlcLor of Lhe efferenL arLerlole. 1he perlLubular
caplllarles arlse from Lhe efferenL arLerlole. So, wlLh vasoconsLrlcLlon of Lhe efferenL
arLerlole, pL ls affecLlng perlLubular caplllarles golng around collecLlng Lubules and renal
medulla. So, ls LhaL produclng lschemla? ?es. So, pL has free rad|ca| damage and
|schem|a |ead|ng to ana|ges|c nephropathy. 1hls ls why Lhe renal papllla necroses,
sloughs off, and leads Lo rena| pap|||ary necros|s. So, asp|r|n and acetam|nophen
tox|c|ty. D|abet|c nephropathy (b]c causes |schem|a), acute pye|onephr|t|s (b]c
abscess format|on), SCDz and tra|t, can a|| |ead to ana|ges|c nephropathy.

243

kV. Chron|c rena| Ia||ure

Def|n|t|on: t has 8UN]Cr rat|o 10:1 for more than 3 months. lf boLh kldneys falled: wlll
noL be able Lo excreLe Lhe Lhlngs we normally geL rld of (so Lhose th|ngs w||| bu||d up le
salL), LC producLlon wlll decrease, leadlng Lo normocyt|c anem|a w|th a corrected
ret|cu|ocyte ct of |ess than 2. Wlll noL be able Lo geL rld of organlc aclds, leadlng Lo
metabo||c ac|dos|s, lncreased anlon gap. WlLh meLabollc acldosls, bones Lry Lo buffer all
Lhe acld. 8/c Lhe bones are bufferlng Lhe exLra P lon, bone dz can develop, leadlng Lo
osteoporos|s. 1he prox Lubules are messed up ln Lhe renal Lubules, and 1-alpha
hydroxylase wlll decrease (Lhls responslble ls hydroxylaLlng vlL u), so, wlLh renal fallure wlll
also have hypov|tam|nos|s D (vlL u def). 1hls means LhaL Lhere wlll be hypoca|cem|a and
hypophosphatem|a, leadlng Lo osteoma|ac|a S osLeoporosls
(b/c bufferlng and wearlng away bone maLrlx) and osLeomalacla, also, 1P ls reacLlng Lo
chronlc hypocalcemla and leads Lo secondary hyperparathyro|d|sm (also affecLs Lhe bone).
1he bun/Cr raLlo ls 80/8. So, lf you know normal renal func you know whaL happens.

kVI. Cther rob|ems re|ated to k|dneys:

Lxample: pL has essenLlal P1n over 10 yrs, and pL ls noL compllanL wlLh medlcaLlon kldney
wlLh cobblesLone appearance = nephrosc|eros|s. underlylng dz causlng lL: hyallne
arLerlolosclerosls b/c Lhere ls decreased blood flow, Lubular aLrophy, glomerull are
flbroslng off, renal funcLlon ls golng down, and leads Lo renal fallure.

Lxample: leLs say Lhe pL wakes up wlLh a blg headache and blurry vlslon. L ls geLLlng dlzzy,
goes Lo dr, and pressure ls 240/140, ln Lhe reLlna, dude has papllloedema wlLh flame
hemorrhages and hard and sofL exudaLes, grade 4 hyperLenslve reLlnopaLhy, 8un/Cr are
80/8 dx? Ma||gnant n1N (aka flea blLLen kldney peLechla vlslble on surface of kldney
8v
peLechlal leslons on Lhe corLex called flea blLLen kldney). 1hls ls all you have Lo know.
1hey can also ask kx: IV n|tropruss|de to get the 8 down. So, Lhey have CnS edema wlLh
8

Lxample: kldney wlLh abnormal areas LhaL are pale and depressed so, lf you Lake a secLlon
Lhrough one of Lhese, and you see an lrregular lrregular pulse, wlll see pale lnfarcLlon wlLh
coagulaLlon necrosls b/c whaL you are looklng aL are |nfarcts. lrregular lrregular pulse ls
from aLrlal flb, and aLrlal flb ls mosL dangerous for embo||zat|on. So, Lhese lnfarcLs are
from mu|t|p|e embo||, leadlng Lo mulLlple pale lnfarcLs of Lhe kldney. 1hls ls nC1
pyelonephrlLls b/c has mlcroabcesses

Lxample: aLrophy due Lo dllaLaLlon of Lhe renal pelvls, leadlng Lo hydronephros|s.
244

So, lf you have hydronephrosls and lncreased pressure presslng on Lhe corLex and medulla,
whaL happens Lo LhaL? Get |schem|a and atrophy wh|ch |s ca||ed compress|on atrophy.
1hls ls very slmllar Lo cysLlc flbrosls ducLs fllled wlLh mucous Lhe pressure ls lmpacLed
back Lo Lhe glands, and Lhey undergo compresslon aLrophy. CorLex and medulla are very
Lhln, along wlLh very dllaLed renal pelvlces. MCC = stone

Lxample: staghorn ca|cu|us ur|ne pn |s a|ka||ne and sme||s ||ke ammon|a, therefore,
there must be a urease producer, and th|s |s roteus. 8]c |t |s a urease producer, Lhey
break urea down Lo ammonla, and geL an alkallne pP. 1hls ls why a staghorn ca|cu|us |s Mg
ammon|um phosphate, and only develops ln lnfecLlons ln pLs LhaL have urease producers.
L coll are noL urease producer and proLeus specles are and Lhey predlspose Lo Lhese sLones.
uo noL pass Lhese sLones (Loo blg), Lherefore need Lo exLracL Lhese (surgery). So, urease
producer, a|ka||ne pn, ammon|a sme|| to the ur|ne.







kVII. 1umors of the k|dney

lf you see a mass ln a kldney, and lLs an adulL, lL ls a rena| adenocarc|noma l
a W S
go Lhere), lLs noL b9, plck cancer.

So, adu|t = rena| adenocarc|noma, k|d = W||ms tumor, they der|ved from the prox|ma|
tubu|e and the MCC = smok|ng, they make |ot of ectop|c hormones: LC, parathyro|d
hormone (|eads to hyperca|cem|a), |nvade the rena| ve|n.
Ce||s are c|ear, fu|| of g|ycogen.

Lxample: flank mass ln chlld, P1n = Wllms Lumor, P1n oc
unllaLeral. PlsLology: cancer where pL ls dupllcaLlng embryogenesls of a kldney everyLhlng
ls prlmlLlve. Can see rhabdomyblasLs, llkes Lo meLs Lo lung
lf / o\ ?\ / & 0 >u ou&u&84 &uuu nt |r|s), and
hem|hypertrophy of an extrem|ty (one extrem|ty |s b|gger than another) th|s |s a s|gn
that the w||ms tumor has a genet|c bas|s.

aplllary leslon ln Lhe bladder = LranslLlonal cell carclnoma (1CC)
WhaL ls Lhe MCC LranslLlonal cell carclnoma of Lhe bladder? Smoklng
245

u A 8 W
Cyclophosphamlde. WhaL are Lhe compllcaLlons of Cyclophosphamlde? Pemorrhaglc
cysLlLls and LranslLlonal cell carclnoma.
Pow do you prevenL Lhls? Mesna.

kVIII. Ur|nary 1ract Infect|on

MC urlne abnormallLy seen ln Lhe lab

Lxample 88C L coll (play
odds). So, &0u>/0?&u7x0uu9u>>u9>>0o these
th|ngs.

,g6--#k> q . PemaLurla ls very frequenL and someLlmes a loL of
blood comes ouL (hemorrhag|c cyst|t|s) and mosL of Lhe Llme lLs L co||, buL someLlmes lL
can be from adenovlrus.

Also, Lhe d|pst|ck has |eukocyte esterase

MosL urlnary paLhogens are nlLraLe reducers, meanlng LhaL Lhey converL nlLraLe Lo nlLrlLe.
Cn a d|pst|ck, they have a sect|on for n|tr|tes. 8/c L coll ls a nlLraLe reducer, Lhere should
be nlLrlLes

So, you have a pL, woman or man, who has dysurla, lncreased frequency, suprapublc paln
88C
leukocyLe esLerase pos, nl = U1I

Is |t |ower or upper? If the pt has fever, f|ank pa|n, W8C casts |ts upper, |f none of these
th|ngs are present, |ts |ower.

Lxample: 88C
esLerase, urlne culLure ls neg, and sexually acLlve person, dx?
Ch|amyd|a norma| ur|ne cu|tures do not p|ck up Ch|amyd|a trachomat|s. It |s the MC
S1D. ln men, called nonspeclflc ureLhrlLls, ln woman lLs called acuLe ureLhral syndrome.
We also use Lhe W
neuLrophll presenL. Cn rouLlne sLool culLure, lLs neg. So, one cause of ster||e pyur|a |s
Ch|amyd|a |nfect|on and the other one |s 18.

246

MC organ that m|||tary 18 goes to = k|dney, therefore w||| have 18 |n the ur|ne, and |t w|||
be ster||e b]c ur|ne cu|tures do not p|ck up. So, remember Ch|amyd|a and 18 as causes of
ster||e pyur|a.