Repro Annotated First Aid 2019

Prepared for students. Amir Mullick -- YouTube.com/USMLELive Best of luck.
HI
GH-
YIELD SYSTEMS
Repr
oduc
tive
“
Arti
fci
ali
nse
mina
tio
niswhe
nthef
arme
rdo
esi
ttot
hec
owi
nst
eado
fthe
bul
l.
”
—St
ude
nte
ssa
y
Makenomis
tak
eabo
utwhyt
hes
ebab
iesa
rehe
re-t
heya
rehe
ret
o
r
epl
aceus
.
—J
err
ySe
inf
el
d
“
Who
eve
rca
lle
ditne
cki
ngwa
sapo
orj
udg
eofa
nat
omy
.”
—Gr
ouc
hoMa
rx
“
See,
thepr
obl
emist
hatGodgiv
esme
nab
rai
nandape
nis
,ando
nly
e
noughbl
oodt
orunoneatat
ime.
”
—Rob
inWi
ll
iams
There produc t
iv
es y
ste
mc anb ei ntimi d
a ti
ngatfir
stbuti smanageable
oncey ouo r
g a
nizethec onceptsi ntot hepr e
gnanc y
,e ndocr
inologi
c,
embryolog i
c,a nd onc ol
ogica spe ct
so freproducti
on. Study the
endocrine and r e
product
ivec ha pter
st oget
her,be ca
us e mast
ery of
t
hehy po t
halamic-
pit
uit
ary-
gonada la x
isi sk e
yt oanswe ri
ngq uest
ions
on ov ul at
ion, me nst
rua
tion, d isorderso fs exual de v
elopment,
cont
race pti
on,andma nypathologies.
Embr y
olog yi
sanua nceds ubjec
tt hatcover
smul ti
pleorgansys
tems.
Approaching itfr
om ac l
ini
c a
lpe r
spect
ive wil
la llo
wf o
r bet
ter
unders
tanding. Forins
tanc e,ma kethe c onnect
ion betweenthe
pre
sentati
ono fDiGeor
gesy ndromea ndthe3r d/
4thpharyngea
lpouch,
and bet
we ent heMülle
rian/Wo l
ffia
ns ys
temsa nddi s
order
so fs
exual
devel
opme nt.
Asforonc olog
y ,don’tworryaboutre memberi
ngscree
ningort r
eat
me nt
guidel
ines.Itismor ei mport
anttok nowho wthe
sec a
ncersprese
nt(eg,
ass
ociat
edl abs,s i
gns,a ndsymp t
oms ),the
irhis
topat
hology,andtheir
und e
rlyi
ngr is
kf actor
s.Ina ddi
ti
on,s omeo ft
het e
sti
cularandov a
rian
cancershaved ist
inctpa t
ter
nsofhCG,AFP,LH,orFSH d e
rangements
t
ha tse
rvea shelpfulcluesinexa
mq ue s
ti
ons
.
5
97
5
98 S ectioNi i i RepRoduct i
ve R E
P ROD UC
TIVE
—E mbRyOl
Ogy
R
EPROD
UCT
IVE
—EmbR
yOl
Ogy
I
mpor
tantgenesofembr
yogenes
is Sonic "runs back and forth" and loses his head (anteroposterior, holoprosencephaly) and WNT-7 is "dorsal-WNTral."
Soni
chedgehoggene Pr
oduceda
tbaseofli
mbsinz
oneofpol
ari
zi
ngac
tiv
ity.I
nvol
vedi
npatt
erni
ngalo
ng
a
nter
opos
ter
iora
xisandCNSdev
elopment
.Muta
tions hol
opr
ose
ncephal
y.
Wnt
-7gene Pr
oducedata
pica
lect
ode
rmalr
idge(
thi
cke
nedectodermatdis
tale
ndofe
achde
vel
opi
ngl
imb
).
Nece
ssar
yforpr
ope
rorg
ani
zat
ional
ongdors
al-
vent
ralax
is.
F
ibr
oblastgr
owth Pr
oduceda
tapi
calec
toder
ma lr
idge.St
imul
at
esmit
osi
sofunderlyingme sod e rm, pr ov idingf o r
Mutations in the FGF receptor 3 results in
fac
tor(F
GF) ge
ne l
engt
heni
ngofli
mbs.“Lookatt tFe
ha t ,Gr
us ngFi
owi nge
rs.
”achondroplasia (autosomal dominant dwarfism).
Homeobox(
Hox
) I
nvol
vedins
egme nt
alo
r g
aniza
tionofe
mb r
yoinac r
ani
oca
uda
ldi
rec
tio
n.Co
def
ort
rans
cri
pti
on
gene
s f
act
ors
.Mutat
ions a ppendag
e si
nwrongloc
ati
ons.
UWORLD= A homeobox is a highly conserved DNA sequence about 180 nucleotides in length.
The 2' oocyte is in the fallopian tube on day 0, arrested at metaphase 2. After fertilization (most commonly in the ampula), it will finish meiosis.
The sperm undergoes acrosomal reaction for gametes to fuse. The acrosome is derived from the golgi apparatus, and the centrioles make up the
Ear
lyf
etaldev
elopment sperm's flagella. By about day 3, the zygote has become the morula.
Ea
rlyembr
yoni
c N=#ofc
hromo
somes
devel
opment C=#of
chro
mati
ds/
DNAc
opi
es
DA
Y1 DA
YS2
-3
Z
ygo
te
(
2N4
C)
DA
Y4
Mor
ul
a
F
ert
il
i
zat
ion
(
2N2
C) Co
rpu
sal
bi
can
s DAY5
DA
Y0 De
vel
opi
ng Bl
ast
ocy
st
f
ol
li
cl
e
Ov
ary DAY
S6 –1
0
I
mpla
ntat
i
on
My
ome
tri
um
Ov
ula
ti
on
2
°oo
cyt
e E
arl
yco
rpu
s
(
1N2
C) l
ut
eum Endo
met
ri
um
Wi
thi
nweek1 hCG s
ecr
eti
onbegi
nsar
oundt
het
imeof Bl
asoc
t y
st“
sti
cks
”a y6.
tda
i
mplant
ati
onofb
las
toc
yst
.
Wi
thi
nweek2 Bi
la
mina
rdi
sc(
epi
bla
st,hy
pob
las
t)
. 2we
eks=2l
aye
rs.
Wi
thi
nweek3 Gast
rulat
ionfor
mst r
ilaminarembryoni
cdisc
. 3we
eks=3l
aye
rs.
Cell
sfrome pi
blas
tinvagina
te primi
tiv
e
s
tr
ea k endoderm, mesoderm,e
ctoder
m.
Notochor
da ri
sesf
rom mi dl
inemesoder
m;
ov
erlyi
nge c
toderm becomesneuralpl
at
e.
Weeks3–8 Neura
ltubef
orme
dbyne
uroe
cto
der
mand Ex
tre
mel
ysus
cept
ibl
etot
era
tog
ens
.
(
embryoni
cper
iod) c
losesbywe
ek4.
Orga
nogenes
is
.
Week4 Hear
tbegi
nstobe
at. 4
weks=4l
e i nd4he
mbsa artc
hambe
rs.
Uppera
ndlowerl
imbbudsbe
gint
ofo
rm.
Week6 Fet
alcar
diaca
cti
vi
tyv
isi
blebyt
rans
vag
ina
l
ul
tra
sound.
Week8 Fe
talmov
eme
ntss
tar
t. Ga
ita
twe
ek8.
Week1
0 Ge
nit
ali
aha
vema
le/
fema
lec
har
act
eri
st
ics
. Te
nit
ali
a.
The ovum is released into the peritineal cavity and gets actively sucked into the uterine tube. It is not directly released into the uterine tube. Sperm can also make it all the way here and
reach the peritineal cavity. So if the ovum is not picked up, fertilization can occur in the peritineal cavity, leading to an ectopic abdominal pregnancy. The major risk is that the placenta will
develop where ever that implantation occurred. Normally, bleeding stops when the smooth muscle of the uterus contracts. But this contraction wont occur in this ectopic space, so bleeding
wont stop, potentially leading to exsanguination.
The mitosis in cleavage is different from usual mitosis because there is no cell growth in between cell divisions, so each cell is tinier than the parent cells. Hence, the total cell
mass is the same for the first few days.
RepRoduct i
ve R E
PRODUC
TIVE
—E mbR
y Ogy S
Ol ecti oNi i
i 5
99
Embr
yol
ogi
cder
ivat
ives
Ec
toder
m Ex
ter
nal
/out
erl
aye
r
Epi
dermi
s;adenohypophysi
s(f
rom Rathke —be ni
gnRa t
hkepo uch
p
ouch);
lensofeye;epi
thel
iall
ini
ngso for
al t
umorwi
thc
hol
est
ero
lcry
sta
ls,c
alc
ific
a t
ions
.
c
avit
y,s
ensor
yo rg
anso fea
r,andolf
actory
e
pit
heli
um; ana
lc analbel
owthep e
ctinat
eli
ne;
p
arot
id,s
we a
t,ma mma rygl
ands.
Bra
in(neur
ohypophy
sis
,CNSneuro
ns,o
lig
o- Ne
uro
ect
ode
rm—t
hinkCNS.
dendr
ocyte
s,as
tr
ocyt
es,epe
ndy
malce
lls
,pine
al
gl
and),r
eti
na,s
pina
lcord.
Melanocytes,Odont oblast
s,Trachea
llining, MOTELPASSES
Entero
chr omaffince l
l,Le
s pt
o meninges Neura
lcr
est
—thinkPNSa
ndno
n-ne
ura
l
(
arachnoid,pia
),PNSg angl
ia(cra
nial,dors
al s
truc
tur
esnea
rby.
r
oot,autono mi
c),Ad renalme dull
a,Schwa nn
ce
ll,Sp
s ir
a lmemb r
ane( aor
ti
copulmo nary
s
eptum),Endo c ardi
alc ushi
ons,Skullbo nes
.
Me
soder
m Mus c
le,bone,conne cti
vetis
sue,serous Middle/me
“ at”lay
er.
l
iningsofbodyc aviti
es(eg,perit
oneum, Mesoderma ldefec
ts=VACTERL:
peri
cardi
um,p leura),s
p l
een(de ri
vedfrom Ver t
ebraldefe
cts
f
oregutme sent
e r
y),cardi
ovascularstr
uc t
ures, Ana latr
e s
ia
l
y mphati
cs,blood,wa l
lofgutt ube,up pe
r Ca rdi
acd efe
cts
vagi
na,kidneys,adrenalcorte
x,de rmis,t
e s
tes
, Tracheo-Esophagealfis
tul
a
ovari
es. Re naldefect
s
Notochordinducese ct
odermt of or
m Limbd efe
cts(boneandmus c
le)
neuroect
oderm( ne ur
alplat
e )
;itsonly
post
natalderiv
ativ
ei sthenuc l
eusp ulposusof
theint
ervert
ebraldisc.
Endoder
m Gutt
ubee pit
he l
ium (includinga nalcanal Ent
“ erna
l”l
aye
r.
a
bovethepe cti
na teli
ne),mos tofurethr
aa nd
l
owervag ina(derivedfrom urog enit
alsi
nus),
l
uminale p i
thel
ia lder
ivati
ves(e g,l
ungs,
l
iv
er,g
allbl a
dde r,pancreas,eustachi
antube ,
t
hymus, pa r
athyro i
d,parafoll
icular(
C)c el
lsof
t
hethyroid.
T
ypesofer
ror
sinmor
phogenes
is
Agenes
is Abs
ento
rga
nduet
oabs
entpr
imo
rdi
alt
is
sue
.
Apl
asi
a Abs
ento
rga
nde
spi
tepr
ese
nceofpr
imor
dia
lti
ss
ue.
Hypopl
asi
a I
ncomp
let
eor
gande
vel
opme
nt;p
rimor
dia
lti
ss
uepr
ese
nt.
Di
srupt
ion 2
°br
eak
downofpr
evi
ous
lynor
malt
is
sueors
truc
tur
e(e
g,a
mni
oti
cba
nds
yndr
ome
).
Def
orma
tion Ext
ri
nsi
cdis
rupt
ion(
eg,mul
ti
pleg
est
ati
ons
cro
wdi
ng
f
ootde
for
mit
ies
);oc
cur
saf
ter
e
mbryoni
cperi
od.
Ma
lfor
mat
ion I
ntr
ins
icdi
sr
upt
ion;oc
cur
sdur
inge
mbr
yoni
cpe
riod(
wee
ks3–8
).
Sequenc
e Ab
nor
mal
it
iesr
esul
tfr
om as
ing
le1
°embr
yol
ogi
cev
ent(
eg,o
lig
ohy
dra
mni
os Pot
ters
eque
nce
).
6
ve R E
P ROD UC
TIVE
—E mbRyOl
Ogy
T
era
togens Mosts
usce
pti
blei
n3 r
d–8 t
hweeks(embr
yoni
cperi
od—orga
nogenes
is
)ofpr
egna
ncy
.Be
for
ewe
ek
3
,“al
l-
or-
none”e
ffe
cts.Aft
erweek8,g
rowthandf
unct
ionaff
ect
ed.
T
ERA
TOg
EN E
FFE
CTSO
NFE
TUS N
OTE
S
ACEi
nhi
bit
ors Re
nalf
ail
ure
,ol
igohy
dra
mni
os,
hypoc
alv
ari
a
Al
kyl
ati
ngagent
s Abs
enc
eofdi
git
s,mul
ti
plea
noma
li
es
Ami
nogl
ycos
ides Ot
otox
ici
ty Ame
ang
uyhi
ttheba
byi
nthee
ar.
Ant
iepi
lept
icdr
ugs Neuraltubedefec
ts,car
diacdefe
cts
,cl
eft Hi
gh-dos
efola
tesupple
me nt
ati
on
pala
te,skel
eta
labnormali
ties(
eg,pha
lanx/
nai
l recomme nde
d.Mos tcommonlyv a
lproat
e,
hypoplasi
a,f
acia
ld y
smo r
phism) c
arbamazepi
ne,phenyto
in,phenobar
b i
tal
.
Di
ethyl
sti
lbes
trol
(DES) Va
gina
lclea
rcel
lade
no c
arc
ino
ma,
cong
eni
tal
Müll
eri
anano
ma l
ies
Fol
atea
nta
goni
sts Ne
ura
ltubede
fec
ts I
nc l
udestr
imethop
rim,me
thot
rex
ate
,
anti
epil
ept
icdrugs
.
I
sot
ret
inoi
n Mul
ti
ples
eve
reb
irt
hde
fec
ts Co
ntr
ace
pti
onma
nda
tor
y.I
soTERATi
noi
n.
L
ithi
um Ebst
einanomal
y(ap
ica
ldi
spl
ace
mentof
tr
icuspi
dval
ve)
Met
himaz
ole Apl
asi
acuti
scongenit
a(cong
eni
tala
bse
nceo
f
s
kin,pa
rti
cul
arl
yo nsca
lp)
T
etr
acy
cli
nes Di
scol
ore
dte
eth,
inhi
bit
edbo
neg
rowt
h Te
“ e
thr
acy
cli
nes
.”
Thal
idomi
de Li
mbd e
fec
ts(
phoc
o me li
a ,mi c rome lia— Limbd efec tswi th“ tha-limb- domi de .
”
“
fip
per”l
imbs
)Thalidomide was prescribed for morning sickness, and over ten thousand babies were born with limb deformities.
War
far
in Bonede
formi
ti
es,
fet
alhemorrhag
e,a
bor
ti
on, Donotwaewa
g rfa
reonthebaby
;kee
pithe
ppy
o
phthal
molog
icabnor
ma l
it
ies wi
thhepa
rin(
doesnotc
ros
spla
cent
a)
.
Al
cohol Commo ncauseofbir
thdef
ectsa
ndi
nte
ll
ect
ual
di
sabi
li
ty;
fet
alalc
oholsy
ndrome
Cocaine inhibits the reuptake of
Coc
aine Lowbi
rt
hweight
,pr
ete
rmb
irt
h,I
UGR, Co
cai
ne
vas
oco
nst
ri
cti
on. monoamines, resulting in sympathetic
stimulation. The vasoconstriction can
p
lac
enta
lab
rupt
ion cause coronary vasospasm in adults.
Smoking Lowbi
rt
hwe ight(
lea
dingcaus
eindev
eloped Ni
cot
ine
vasoc
ons
tr
ict
ion.Second hand smoke (SHS) has a high risk
of SIDS. Up to half of all SIDS cases are
(
nic
otine,
CO) c
ount
rie
s),p
reter
ml a
bor,
place
nta
lprobl
ems, CO i
mpa
ire
dO2deli
very.due to SHS, likely due to impaired arousal.
Warn parents who smoke outside the home
I
UGR,SIDS,ADHD about cessation since chemicals come in.
I
odi
ne(
lac
korex
ces
s) Co
nge
nit
alg
oit
ero
rhy
pot
hyr
oidi
sm(
cre
tini
sm)
Mat
ernal
diabet
es Caudalregr
essi
ons y
ndrome( analatr
esiat
o The infant will have transient hypoglycemia. In pregnant women with poorly
controlled diabetes mellitus, the fetus is subjected to high blood glucose levels
si
renomeli
a),congeni
talhear
tde f
e c
ts(eg
, since glucose crosses the placenta; however, maternal insulin is unable to cross
VSD,t r
anspos
iti
ono ft
heg re
a tve
s s
els
), the placenta. The fetal hyperglycemia leads to a compensatory rise in fetal insulin
production and islet cell hyperplasia. Fetal hyperinsulinemia promotes abnormal
neuralt
ubed efe
cts
,ma cro
somi a,neonat
al fetal growth, resulting in macrosomia. After birth, the hyperinsulinemic state
persists for several days. It will resolve within a week.
hypogly
cemia,polycyt
hemia
Met
hyl
mer
cur
y Ne
uro
tox
ici
ty Hig
hesti
ns wo
rdfis
h,s
har
k,t
il
efis
h,k
ing
mack
e r
el.
Vi
tami
nAex
ces
s Ext
remel
yhi
ghri
skforsponta
neousabor
ti
ons
a
ndb i
rt
hdef
ect
s(c
leftpala
te,c
ardi
ac)
X-
ray
s Mi
croc
epha
ly,i
nte
lle
ctua
ldi
sab
ili
ty Mi
nimi
zedb
yle
ads
hie
ldi
ng.
RepRoduct i
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PRODUC
TIVE
—E mbR
y Ogy S
Ol ecti oNi i
i 6
01
Fetal
alcohol Oneo ftheleadingpr ev
e ntabl
ecausesofint
e l
lect
ualdisabi
li
tyintheUS. Newbo rnso fmother
s
syndrome whoc onsume da lcoholduringanysta
g eofpregnancyha ve i
ncidenceofconge nit
al
A
abnormalit
ies,includi
ngpr e-andpostnata
lde ve
lopme nta
lretar
da t
ion,mic
rocepha ly
,fac
ial
abnormalit
iesA ( eg,s
mo ot
hphi l
tr
um, thi
nv ermill
ionbord e
r,smallpal
pebralfiss
ures
),l
imb
dis
locati
on,he artdefe
c ts
.He ar
t-
lungfis
tulasandholoprosencephalyinmostseve r
eform.One
me cha
nismi sd uet oi
mp a i
redmigrat
iono fneuronalandglialcel
ls.
Neonatal
abs
tinenc
e Complexdis
orderinvolv
ingCNS, ANS, a ndGIs yst
ems.Secondarytoma t
ernalopi
at
euse/
abus
e.
syndr
ome Univ
ers
alscr
e eni
ngfo rs
ubstanceabuseisr e
c ommendedina l
lpregnantpat
ients
.
Newbor
nsma ypre
sentwi t
hunc oo
rdinateds ucki
ngrefexes
,ir
rit
abil
it
y,hig
h-pit
chedcry
ing
,
t
remors,
tachypnea,sneezi
ng ,
diarr
hea,a ndpossi
blyse
izures
.
UWORLD= A 2 day old girl is in the newborn nursery with persistent crying, tremors, tachypnea, sneezing, and diarrhea. She was born vaginally and had been breastfeeding well until several
hours ago when she became tachypneic. Her mother has poorly controlled schizophrenia and did not receive prenatal care. The patient's mother also had a positive hepatitis C antibody test
during postnatal lab testing. On physical exam, the girl has increased tone in all extremities and is irritable but quiets when swaddled. Chest radiograph shows normal lung fields. What is the
most appropriate pharmacotherapy for treatment of the newborns symptoms? Methadone. This newborn has signs of neonatal abstinence syndrome due to opiate withdrawal. The treatment of
choice is usually morphine or methadone and the dose is gradually increased until symptoms are controlled, and then the patient is weaned off over several weeks.
6
ve R E
P ROD UC
TIVE
—E mbRyOl
Ogy
T
winni
ng Di
zygoti
c(“fra
ter
na l
”)t winsa r
isefrom 2e ggstha tarese pa r ate lyf e rt
ilize dby2di ff
erentsper
m
(
al
wa y
s2z ygot
es)andwi llhave2s eparat
ea mni oticsac sa nd2s epa ra t
ep la ce nt as(chori
ons)
.
Monozygot
ic(“i
denti
c al
”)t winsaris
efr o
m 1fer t
il
iz edegg( 1e g g+1s p erm)t ha ts pli
tsinearl
y
p
regnancy
. Thetimingofc l
e a
vagede ter
mine scho ri
onici ty( numbe ro fc ho rions )anda mnionic
ity
(
numb erofamnions)(SCAB) :
Cleavage0–4da ys:Se parat
ec horionanda mni on Or think of it as "Share nothing."
Cleavage4–8da ys:sha r
edCho rio
n
Cleavage8–12da ys:sha r
edAmni on
Cleavage13+da ys:sharedBody( conjoi
ned)
Di
zygot
ic(
fr
ate
rna
l)[
~2/
3] Not
winn
ing Mo
noz
ygo
tic(
i
den
tic
al)[
~1/
3]
2egg
s, 1e
gg,
1sp
erm
2s
per
m
2
-ce
lls
tag
e 2
-ce
lls
tag
e 2
-ce
lls
tag
e
Di
cho
ri
onic
0–4da
ys Cl
eav
age
di
amni
ot
ic[
25%]
2
-ce
lls
tag
e Mo
rul
a B
las
toc
yst
Mor
ul
a Mo
rul
a Mo
rul
a
Cl
eav
age Mono
chori
oni
c
4
–8da
ys
di
amni
ot
ic[
75%]
B
las
toc
yst B
las
toc
yst B
las
toc
yst
Cl
eav
age Monoc
hor
ion
ic
8
–12d
ays monoa
mni
oti
c
[
ra
re]
Ch
ori
oni
c A
mniot
i
c
cav
it
y c
avi
t
y
F
orme
d F
orme
d F
orme
d
e
mbry
oni
cdi
sc e
mbry
oni
cdi
sc e
mbry
oni
cdi
sc
Monoc
hor
ioni
c
Cle
avageo
r
>1
3da
ys monoa
mniot
i
c
a
xisdup
li
cat
i
on [
con
joi
ned
—rare
]
Ch
ori
on
(
out
er)
A
mn i
on
(
i
nner
) End
ome
tr
iu
m
Di
chor
i
oni
c Notwi
nningi
f
di
amni
oti
c n
oc l
eav
age
RepRoduct i
ve R E
PRODUC
TIVE
—E mbR
y Ogy S
Ol ecti oNi i
i 6
03
Pl
acent
a 1
ºsi
teofnut
ri
enta
ndg
ase
xcha
ngebe
twe
enmot
hera
ndf
etus
.
Cyt
otr
ophobl
ast I
nne
rla
yerofc
hor
ioni
cvi
ll
i. Cy
tot
rophob
las
tma
kesCe
lls
.
S
ync
yti
otr
ophobl
ast Oute
rlaye
rofchorio
nicvil
li
;synthesi
zesand Sy
nc yt
iotr
ophobl
astsynt
hesi
zeshor
mo ne
s.
s
ecret
eshor
mo nes,eg
,hCG ( s
truct
urall
y LacksMHC- Iexpr
e s
si
on chanceofat
tac
k
s
imil
artoLH;stimulat
escor
pusl ut
eum to byma te
rnali
mmunes ys
tem.
s
ecret
eprog
est
e r
oneduringfir
sttri
mester
).
Dec
iduaba
sal
i
s Der
ivedf
rom e
ndo
met
ri
um.
Mat
erna
lbl
oodi
n
l
acunae
.
E
ndo
met
ri
al
vei
n Mat
er
nal
B
ran
chv
il
lu
s E
ndo
met
ri
ala
rt
ery ci
r
cul
at
io
n
Umb i
l
ica
lve
in Ma
ter
nal
cir
cul
at
io
n
(O2r
ic
h)
O2
Umb
il
ic
a la
rt
eri
es H2O,el
ect
rol
yt
es
(O2poor
) Nutr
ie
nts
Hormones
I
gG
Drugs
F
eta
lci
r
cul
at
io
n Vi
ruse
s
CO2
H2O
Ure
a,was
tep
rod
uct
s
Hormon
es S
ync
yti
ot
ro
pho
bla
st
C
yto
tro
pho
bla
st
E
ndo
the
li
alc
ell
A
mni
on
Ch
ori
oni
cplat
e
Mat
ern
alb
lood De
cid
uab
asa
li
s
The 3 layered, flat body form will now start becoming round in the 4th week. The embryo will fold around
as the lateral sides start curving until the edges fuse, and the yolk sac detaches. Now you have 3 tubes,
a tube inside a tube inside a tube. The innermost tube is the gut tube which opens from the mouth to the
anus. The upper layer of the ectoderm will be the epidermis of our skin. The middle layer will give the
mesodermal derivatives. In order for this to happen normally, the lateral body folds had to fuse perfectly
to give the ventral body fold.
Gastroschisis is a ventral wall defect where the left and right body folds have a defective fusion, allowing
the small intestine to plop out such as in the image below. The green arrow is pointing at the umbilical cord.
Another similar defect is an omphalocele, where the gastric contents are still inside the umbilical cord.
6
ve R E
P ROD UC
TIVE
—E mbRyOl
Ogy
Umbi
li
cal
cor
d Twoumbi l
icala
rteri
esr e
turnd eoxyg
enat
ed Si
ng l
eumbi l
icalar
ter
y(2-
ves
selc
o r
d )i
s
bl
oodf r
om fet
alint
e rnalil
iacart
eri
esto ass
ociat
edwithc o
ng e
nit
ala
ndc hromosomal
pl
acentaA. anoma l
ies
.
Oneumbi li
calve
insuppl ie
sox y
g e
natedbl
ood Umbi l
ica
larte
riesandvei
narederi
vedfrom
f
rom place
ntatofetus;drai
nsintoIVCv i
a all
antoi
s.
l
ive
ro rvi
aduc t
usve nosus.
A
Umb
il
ic
ala
rte
ry Umb
il
ic
ala
rte
ry
Umbil
i
cal
Al
l
ant
oi
cdu
ct Umbi
li
cal
ar
ter
i
es
ve
in
Umbil
i
cal
A
ll
ant
oi
cduct
s ve
in
A
mniot
ice
pit
hel
i
um Wh
art
onj
el
ly Co
rdl
i
nin
gme
mbr
ane
Whar
ton
j
el
ly
Ur
achus I
nt he3rdweektheyo l
ks acfor
mst heall
antoi
s,whi
chextendsi
nt ourogeni
talsi
nus.Alla
ntois
becomestheur a
chus,ad uctbetweenfet
albla
dderandumbi l
icus.Fai
lureofurac
hust oinvol
ute
canleadtoanoma l
iesthatma yincr
easeri
skofinf
ect
ionand/orma li
gnancy(eg,
adenocarc
inoma)
i
fno tt
reat
ed.
Oblit
era
tedurachusisrepres
entedbytheme dianumbil
ica
lliga
me ntaf
terbi
rth,whichiscover
ed
byme dia
numbi li
calfoldofthepe r
it
oneum.
To
talf
ail
ureo
fur
achust
oobl
it
era
t ur
e i
nedi
scha
rgef
rom umb
ili
cus
.
Par
ti
alf
ail
ureofura
chust
oobli
ter
ate
;fui
d-fil
ledcav
ityl
inedwit
hur
oepi
the
li
um,betwe
en
umbil
ic
usandb l
adde
r.Cys
tcanbecomeinfecte
dandp re
senta
spa
inf
ulmassbe
lowumbi
li
cus
.
Sl
ightf
ail
ureo
fur
achust
oobl
it
era
te
out
pouc
hingofbl
adde
r.
Umb
il
ic
us
No
rma
l P
ate
ntu
rac
hus Ur
ach
alc
yst V
esi
cou
rac
hal
div
ert
i
cul
um
Vi
tel
li
neduc
t 7
thweek—obl
it
era
ti
onofv
it
ell
ined
uct(
ompha
lome
sent
eri
cduc
t)
,whi
chc
onne
ctsy
olks
act
o
mi
dgutlume
n.
Vi
tel
li
ned
uctf
ail
stoc
los
e
mec
oni
um di
scha
rgef
rom umbi
li
cus
.
Pa
rti
a lc
los
ureofvi
te
lli
ned
uct,wit
hpat
entport
iona
tta
chedtoil
eum (
tr
uediv
ert
icul
um,whit
e
ar
rowinA) .Mayhavehet
ero
topi
cga
str
icand/
orpancr
eat
icti
ss
ue me l
ena
,hematoc
hezi
a,
a
bd ominalpa
in.
A
Umb
il
ic
us
No
rma
l V
it
el
li
nefi
stu
la Me
cke
ldi
ver
ti
cul
um
RepRoduct i
ve R E
PRODUC
TIVE
—E mbR
y Ogy S
Ol ecti oNi i
i 6
05
Aor
ticar
chder
ivat
ives De
vel
opi
ntoa
rte
ria
lsy
ste
m.
1
st Pa
rtofmaxi
ll
arya
rte
ry(
bra
nchofe
xte
rna
l 1
sta
rc sma
hi xima
l.
ca
rot
id)
.
2nd St
ape
dia
lar
ter
yandhy
oida
rte
ry. Se
cond=St
ape
dia
l.
3r
d CommonCar
oti
dart
erya
ndp
rox
ima
lpa
rtof Ci
s3r
dle
tte
rofa
lpha
bet
.
i
nte
r lCa
na rot
idar
ter
y.
4t
h Onleft
,aor
ti
carch;onri
ght
,pr
oxi
malpa
rtof 4t
har
c 4l
h( i )=s
mbs yst
emi
c.
r
ights
ubcla
via
na r
tery
.
6t
h Pr
o x
imalpar
tofpul
mo nar
yar
ter
iesa
nd(
onl
eft 6t
harch=pul
monar
yandthepulmona
ry-
to-
only
)duct
usart
eri
osus
. s
yst
emics
hunt(
duc
tusa
rter
ios
us)
.
3
rd 3
rd
A 4yo boy is being evaluated for failure to thrive, SOB, and 4

th
exercise intolerance. Cardiac exam shows bounding peripheral
pulses and a palpable thrill over the left upper sternal border.
On auscultation, a continuous murmur is best heard over the Ri
ghtr
ecur
ren
t 4
th L
same region. If surgery is planned, the surgeon should intervene eft
rec
urr
entl
ar
ynge
alne
rve
on a derivative of what embryologic structure? Sixth aortic arch. l
ar
yngeal
nerv
e l
oopsa
rou
ndaort
i
carchd
ist
al
The patient most likely has a patent ductus arteriosus, an l
oopsar
oundri
ght t
oduct
usar
te
ri
osus
embryonic derivative of the sixth aortic arch that allows fetal s
ubcl
avi
anart
ery 6
th
blood to pass directly from the pulmonary artery to the proximal
6
th
descending aorta (bypassing pulmonary circulation).
T
run
cusa
rt
er
io
sus
De
sce
ndi
nga
ort
a
6mon
thspo
stn
ata
l
Phar
yngeal
appar
atus Compo s
edofpha r
yngealclef
ts,ar
ches
, CAPc ov e
rsoutsi
detoins
ide:
pouches
. Clefts=e ct
oderm
Phary
ngealcleft
s—d eri
vedfrom ect
oderm.Als
o Ar
c he s=me soder
m +ne ur
alc
res
t
cal
ledpharyngealgrooves. Pouche s=e ndoder
m
Phary
ngealarches—d er
ivedfrom mesoder
m
(muscl
es,ar
teri
e s
)andne uralcr
est(
bones, P
har
yng
eal
floo
r
car
til
age)
. Ca
rt
il
age
Phary
ngealpouc hes
—de ri
v e
df ro
me ndoderm. I r
Neve
A
rte
ry
I
I
I
I
I
I
V
Cl
ef
t
Ar
ch V
I
Po
uch
Also called pharyngeal groove.

Pharyngeal
clef
t 1stc
leftde
vel
opsintoe x t
e rna la udi toryme a tus.
deri
vati
ves 2ndthrough4thclef t sfor mt e mpor aryc e rv ica
l sinus e s,whi cha reob lit
er ate dbypr oliferatio nof2nd
archme s
enchyme .
Pers
ist
entcer
vic
alsinus pha ryng e alc leftc ystwi thi nl a te ralne c k,a nteriort os terno cleido ma s t
oid
mus c
le. You'll have a child with a painless lump on the side of the neck that does not move when he swallows.
Ectopic thyroid tissue will move with swallowing.
UWORLD= A 3 week old boy with discharge from the umbilicus is brought to the clinic. His postnatal course was uncomplicated, with shriveling of the cord around 14 days of life. Vital signs are
normal. Exam of the area reveals a small reducible umbilical hernia, minimal clear to straw-colored discharge from the umbilicus, and erythema around the area. Lab results show high neutrophils
and lymphocytes. What is the most likely cause of the childs condition? Persistence of allantois remnant. He has a patent urachus.
A 3yo boy is brought to the ED after he develops acute abdominal pain and vomiting. Imaging studies reveal a foreign body lodged within his intestine causing a small bowel obstruction.
Laparotomy is performed to remove the foreign body; during the procedure, an incidental abdominal cyst is discovered and removed. The cyst is connected by a fibrous band to the ileum and
umbilicus. What condition is also caused by the same embryological defect responsible for this patients abdominal cyst? This patient has a vitelline duct cyst, and Meckel's diverticulum is the
most common vitelline duct anomaly. Remember the rule of 2's for Meckel diverticulum; 2% of population, 2 feet from ileocecal valve, 2 inches in length and males are 2
times more likely to be affected.
6
ve R E
P ROD UC
TIVE
—E mbRyOl
Ogy
Phar
yngeal
arc
hder
ivat
ives Also called branchial arches.
A
RCH C
ART
IlA
gE mU
SCl
ES N
ERV
ESa N
OTE
S
1
stphar
yngeal Ma xi
lla
rypr ocess Mus cl
esofMa sti
cati
on CNV3c he w —
arch Max i
ll
a ,zygoMa t
ic (t
empor ali
s,Ma sset
er, Cranial Nerve 5.3
micr
og nat
hia,
bone lat
eralandMe dial Maxilla, Mastication, gl
oss
opt o
sis
,cl
eft
and Music.
Ma ndibul
arpr ocess pter
ygoids,My
) l
ohyoid, pal
at
e ,ai
rway
Mec k
elc arti
lage anter
iorbellyofdigastr
ic, V3 is also the nerve obs
tructi
on
responsible for
Mandib le, tens
orty mpa ni,a
nteri
or general sensation of
the anterior 2/3 of the
Ma ll
eusa ndi ncus, 2
⁄
3oftongue,t e
nsorveli tongue. —a ut
osoma
l
sphenoMa ndibula
r pala
tini domi nantneural
li
game nt cres
td y
s f
uncti
on
2ndpha
ryngeal Rei
c hertcar
ti
lage
: Musc l
esoffac
ialex
press
ion, CN VI I(fa cia l
c r
aniofac
ial
ar
ch Stapes,Sty
loi
d Stapedi
us,Sty
lohyoi
d, expr es si
on ) abnorma li
ti
es(e
g,
process,l
ess
erhorn pla
tySma ,pos
ter
iorbel
ly smi le zygoma ti
cbone
ofhy o
id,Styl
ohyoi
d ofdigas
tri
c Cranial Nerve 7 andma ndibular
Smile, Stapes and
li
ga ment Styles. hypoplasi
a),
heari
ngl oss
,air
way
compr o
mi se
3rdpha
rynge
al Gr
eat
erho
rno
fhy
oid St
ylo
pharyng
e us(
think CN I
X( s
tylo-
arc
h ofs
tyopha
l rynge
us p
haryngeus)
i
nnerva
tedby s
wall
ows tyl
is
hly
gl
osopha
s ryngealner
ve)
4th–6th Ary
teno
i ,Cr
ds icoi
d, 4t
ha rch:mostpha r
yngeal 4t
harch:CN Ar
c hes3a nd4f or
m
pharyngeal Corni
cul
ate
, constr
ict
ors
; c
ricot
hyroid, X(s
upe r
ior poste
rior1⁄
3oftongue;
arches Cunei
fom,Thy
r r
oid l
e v
atorvel
ipalati
ni l
aryngea
lbranch) a rch5ma kesno
(
usedtos
ingand 6t
ha rch:al
lint
rinsi
c s
implyswa l
low ma j
orde vel
opme nt
al
ACCCT) musc l
esoflar
ynxe xc
e pt 6t
harch:CN contri
butions
cri
cothyr
oid X(r
e c
urrent
/
i
nferi
orla
ryngeal
br
anch)speak
aSe
nsor
yandmot
orne
rve
sar
enotpha
ryng
eala
rchde
riv
ati
ves
.The
ygr
owi
ntot
hea
rche
sanda
red
eri
vedf
rom
ne
uroe
ctode
rm.
Whenatt
heres
taur
antoft
hegol
dena
rches
,chi
ldr
ent
endt
ofir
stc
hew(
1)
,t ns
he mi
le(
2),t
hens
wal
lows
tyl
is
hly(
3)o
r
s
impl
yswal
low(4)
,andthens
peak(
6).
Top two images -

Pierre Robinson Sequence
Bottom two photos -

Treacher Collins Syndrome
RepRoduct i
ve R E
PRODUC
TIVE
—E mbR
y Ogy S
Ol ecti oNi i
i 6
07
Phar
yngeal
pouc
hder
ivat
ives Also known as branchial pouch.
P
OUC
H D
ERI
VAT
IVE
S N
OTE
S mN
EmO
NIC
1
stpha
ryngea
lpouc
h Middl
eea
rc a
vit
y,e
ustac
hia
n 1
stpouc hcontri
butesto Ea
r,tonsil
s,bott
om- t
o-to
p:
t
ube,mas
toi
daircel
ls
. endoderm-li
neds t
ructuresof 1(e ar
),
ear
. 2(tonsil
s)
,
2ndpha
rynge
alpouc
h Epi
the
lia
lli
ningofpa
lat
ine 3d ors
al(bott
omf orinf
eri
or
t
onsi
l. parat
hyroi
ds)
,
3v ent
ral(o=t
t hy
mus ),
3r
dphar
yngeal
pouc
h Dors
alwings i
nfer
ior 3
rdpouc hc ontr
ibute
st o3
4(top=s uper
ior
p
arat
hy r
oids
. st
ructure
s( t
hymus ,l
eftand
parat
hyroi
ds)
.
Ve
ntralwings thy
mus. ri
ghtinfer
iorparat
hy r
o i
ds)
.
3
rd-pouchstructure
se ndup
below4 t
h-pouchs t
ructures
.
4t
hphar
yngea
lpouc
h Dors
alwings s
uperior
p
arathyr
oids.
In this image to the right you can see
Ve
ntralwings the 3rd pouch has yellow and red
parts, for the dorsal and ventral wings.
ult
imopharyngealbody The same is true for the 4th pouch, which
paraf
oll
ic
ular(C)cell
sof has a yellow and blue part.
t
hyroid. The yellow parts give the parathyroids,
and its important to remember them.
Cleftl
ipandc
lef
t Cl
eftli
pA—f a
il
ureoff
usi
onofthemaxil
lar
y
Roofof Nas
al
palate a
ndme r
gedme di
alna
salpr
oce
s s
es(
for
ma t
ion mout
h ca
vit
y
A o
f1 °pal
ate
). (
1°pa
la
te)
Cl
eftpala
te—fail
ureoffusi
onofthetwola t
era
l
pal
ati
neshel
vesorfai
lureoff
usi
onofl a
teral
pal
ati
neshel
fwiththena s
als
eptum and/or Pal
at
ine
medianpal
ati
neshelf(f
ormat
ionof2°pa la
te)
. s
hel
ves
(
2°pal
at
e)
Cl
eftl
ipandcl
eftpal
atehav
edist
inc
t,
mult
if
act
ori
aleti
olo
gies
,buto
fte
noc c
ur Uv
ula
t
oget
her. Cl
ef
tpa
lat
e(p
art
i
al)
6
ve R E
P ROD UC
TIVE
—E mbRyOl
Ogy
Geni
tal
embr
yol
ogy
Fe
mal
e Def
aultdevel
opment
.Mes
one
phr
icduc
t
d
egene r
ate
sandpar
ame
sone
phr
icduc
t
d
evel
o ps.
Me
son
eph
ros
Mal
e SRYg eneo nYc hromosome —pr oduce ste
sti
s- Gu
ber
nac
ulu
m
dete
rmi ningfactor t
estesdevelopme nt. P
ara
mes
one
phr
i
cdu
ct
Ser
tolicell
ss ec
reteMülleri
aninhibitory Mes
one
phri
cduct
fa
ctor( MIFa ls
ok nowna s
, a
ntimul l
erian Ur
ogeni
t
als
inu
s
hormo ne)thatsuppres
sesdevelo
pme ntof
parame sonephri
cduc t
s.
Leydi
gc el
lssecr
eteandrogensthatsti
mul ate Te
sti
s-
dete
rmi
ni
ngf
act
or
And
rogens Noa
ndr
oge
ns
developme ntofme s
onephricduc ts
. MI
F
Par
amesonephr
ic Devel
opsintofemaleinter
nalst
ructure
s— E
pid
idy
mis
(
Müll
eri
an)duc
t f
all
opiantubes,ute
rus,upperport
ionofva
gina T
est
i
s Ov
ary
Met
anep
hri
c
Paramesonephric duct has "para" in it for the
(
lowerporti
on f
rom ur
ogeni
talsi
nu s
).Mal
e ki
dne
y
parallel fallopian tubes & breasts of a woman. r
emna ntisappendixtes
ti
s.
Mullerian is for Mother. "Paramullerian."
Mesonephric does not have "para" because Ov

idu
ct
there is one penis. Associate
—ma yprese
nt
a Wolf with a man; Wolffian. a
s1°amenor
rhea(
duetoalackofuteri
ne Ur
ina
ry
Ur
ete
r
Mullerian agenesis also has a blind d

evel
opment
)infe
ma l
eswithf
ullydevel
oped bl
add
er
ending vagina with no cervix or uterus. 2
°sexua
lchar
act
eri
st
ics(
funct
ionalovar
ies
). De
me
g
s
e
n
o
e
n
e
r
p
a
t
h
e
r
d
i
c
De
gen
e r
at
ed du
ct
Mesone phric Devel
opsint
oma leint
ernalstr
ucture
s(e
xcept p
ara
mes
one
phr
icduc
t
(
Wolffian)duct pros
tat
e)
—Se minalves
icle,Epi
s didymi
s, V
asd
efe
ren
s
Ut
eru
s
V
agi
na
Ejac
ulat
oryduc,Duc
t tusdefer
ens(SEED).
Femaleremnanti
sGa rt
nerd uct
.
Sexual
differ
ent
iat
ion Abs e
nc eofSe rtolice l
lsorla c
kofMül leri
an
inhibit
oryfactor de v
elopbo thma leand
Un
diffe
go
re
na
n
t
d
i
s
a
ted f
e ma l
einternalg eni t
a l
iaandma leexternal
genital
ia
Me
dul
l
a Co
rte
x
5α-reductasede fici
e ncy—ina bil
itytoconv er
t
Mes
on eph
ric
(
S
X
R
Y
Y
)
X
X
(
noS
RY)
P
a r
amesonep
hri
c t
e s
toster
onei ntoDHT ma leinter
na l
(
Wol
ffia
n)duct (Müll
eri
an)
duct
genital
ia,ambi guo use xter
na lgenit
aliauntil
L
eydi
g
T
est
es
S
ert
oli
Ov
ari
es
pube rt
y(whe n t estost
eronel evel
sc a
use
c
ell
s ce
ll
s
ma sculi
nizati
o n)
Q
I
nthet est
es:
T
est
ost
er
one MI
F E
str
adi
ol
R
Le ydigLe a
dst oma le( i
nternalande xternal
)
5
α-r
educ
tas
e
sexualdiff
erent iat
io n.
Se r
toliShutsdo wnf ema le(int
e r
na l
)sexual
Di
hyd
rot
est
ost
er
one diff
e r
enti
ation.
UWORLD= A 32yo woman, G2P1, with an uncomplicated prenatal course delivered
a 9lb newborn at 39 weeks gestation via spontaneous vaginal delivery. Apgar scores
I
nte
rna
lmale E
xte
rnal
male E
xte
rnalf
emal
e I
nte
rnalf
emal
e were 8 and 10 at 1 and 5 minutes, respectively. Further evaluation in the newborn
geni
ta
li
a geni
ta
li
a geni
ta
li
a gen
ita
li
a
nursery shows abnormal sexual differentiation. Karyotype analysis shows 46, XY.
Semin
alves
ic
le Pe
nis Cli
tor
is F
all
opi
ant
ubes Biopsy of gonadal tissue shows a lack of Sertoli cells but normal Leydig cells. What
Ep
idi
dymi
s S
crot
um Lab
ia Ut
er
us phenotype will most likely be present? Female and Male internal, with Male external.
Ej
acul
at
oryduc
t Di
st
alv
agi
na P
roxi
malv
agi
na Testis contain both sertoli and leydig cells. Sertoli cells suppress female internal
+P
ros
tat
e
Duct
usdef
ere
ns reproductive organs by producing anti-Mullerian hormone, Leydig cells secrete
testosterone to stimulate Wolffian ducts for male internal and external organs.
Sertoli and Leydig cells are the hormone-producing cells of the testis. Leydig cells, which are analogous to female theca cells, produce testosterone in response to LH stimulation. LH is released
from the anterior pituitary in response to GnRH from the hypothalamus. Testosterone release causes feedback inhibition of both LH and GnRH release. Sertoli cells, which are analogous to
female granulosa cells, produce inhibin in response to FSH from the anterior pituitary. Inhibin suppresses FSH production by the anterior pituitary, although it does not feed back on the
hypothalamus. Sertoli cells facilitate the spermatogenesis within seminiferous tubules. Selective impairment in Sertoli cell function would cause decreased inhibin and lead to increased FSH,
as well as infertility due to impaired sperm production.
RepRoduct i
ve R E
PRODUC
TIVE
—E mbR
y Ogy S
Ol ecti oNi i
i 6
09
Ut
eri
ne(
Mül
ler
ianduc
t)anomal
ies
Sept
ateut
erus Commonanomalyv
snor
malut
erusA.I
ncompl
etere
sor
pti
onofs
ept
um B.
f
ert
il
it
yande
arl
y
mis
car
ri
age
/pr
egna
ncyl
oss
.Tr
eatwi
ths
ept
opla
sty
.
Bi
cor
nua
teut
erus I
ncompl
etef
usi
onofMül
le
ria
nduc
tsC.
ri
skofc
ompl
ica
tedp
reg
nanc
y,e
arl
ypr
egna
ncyl
oss
,
mal
pre
sent
ati
on,
pre
mat
uri
ty.
Ut
erusdi
del
phy
s Comp
let
efa
il
ureoff
usi
on
doubl
eut
erus
,ce
rvi
x,v
agi
naD.
Pre
gna
ncypos
si
ble
.
UWORLD= A 25yo woman g4, p0, comes to the

office for evaluation of recurrent pregnancy loss.
She has had 4 second-trimester losses with the
same partner. The patient has menstrual cycles
approximately 28 days with light bleeding for
2-3 days. Her past medical history is significant Nor
mal S
ept
ate B
ico
rnu
ate Di
del
phy
s
for left renal agenesis. Family history is negative
for pregnancy loss. Lab studies are negative for A B C D
anticardiolipin antibodies and lupus anticoagulant.
Results of the patient's hysterosalpingogram are
shown and resembles image C. A pelvic MRI is
ordered and shows an abnormal contour to the
uterine fundus. Failure of which process is the
most likely underlying mechanism of her issue?
Lateral fusion of paramesonephric ducts. That is
another name for the Mullerian ducts. Developing
of the paramesonephric and mesonephric ducts
are closely linked, so uterine anomalies often
coexist with renal anomalies like in this patient.
Failed lateral fusion leads to bicornuate uterus.
Mal
e/f
emal
egeni
tal
homol
ogs
Ma
le F
ema
le
Gl
ansp
eni
s Gen
it
al
Ge
nit
alg
roo
ve t
uber
cl
e
P
eni
l
eur
et
hra Ur
oge
nit
al
f
ol
d L
abi
osc
rot
al Cl
i
tor
i
s
s
wel
li
ng
Ur
oge
nit
al La
bia
Op
eni
ngof
s
in
us mi
nora
ur
et
hra
S
cro
tum La
bia
Op
eni
ngof maj
ora
A
nus v
agi
na
Ur
ach
us A
ll
ant
oi
s Ut
er
in
e
V
esi
cal Ur
ach
us
K
idn
ey t
ube
Ur
ina
ry p
art Ur
ina
ry
bl
add
er Geni
ta
l K
idn
ey
P
elv
ic Ur
ogeni
t
al bl
adde
r
t
ube
rcl
e p
art s i
nus
Te
sti
s Cl
i
tor
is Ov
ary
Gl
ans
pe
nis Ur
eter P
hal
li
c
p
art Ut
er
us
Duct
us R
ect
um
S
pongy def
er
ens
ur
et
hra V
agi
na
Di
hyd
rot
est
ost
eron
e E
str
oge
n
Gl
anspeni
s Ge
nit
alt
ube
rcl
e Gl
ansc
li
to
ri
s
Cor
puscav
e r
nosu
m
andspo
n gi
osu
m Ge
nit
alt
ube
rcl
e V
est
i
bul
arb
ulb
s
B
ulb
oure
thr
a l
gla
nds Gr
eat
erves
ti
bula
rgl
ands
(ofCowper
) Ur
oge
nit
als
in
us (
ofBa
rth
oli
n)
P
ros
tat
egl
and Ur
eth
rala
ndp a
raur
et
hra
l
Ur
oge
nit
als
in
us gl
and
s(ofSk
ene)
V
ent
ra
lsh
afto
fpeni
s
(
peni
l
eu r
et
hra
) Ur
oge
nit
alf
ol
ds L
abi
ami
nor
a
S
cro
tum L
abi
osc
rot
als
wel
l
ing L
abi
ama
jor
a
6
ve R E
P ROD UC
TIVE
—ANA TOmy
Congeni
tal
peni
leabnor
mal
it
ies
Hypos
padi
as Abnormalopeni
ngofpenil
euret
hraonvent
ral Hypospadia
sismorec ommo nt
han
sur
faceofpe
nisduetofa
ilur
eofure
thr
alfo
lds e pi
spadias
.Assoc
iate
dwi t
hingui
nalhe
rni
a,
t
ofuse. cry
ptorchi
dis
m,c hordee(
downwar
dorupwar
d
bendingofpenis
).
Hypoi sbel
ow.
Epi
spadi
as Abnormalopeni
ngofpenil
eurethr
ao ndors
al Exs
tr
ophyoftheb
ladderi
sas
soc
iat
edwit
h
surf
aceofpe
nisduetofa
ultyposi
ti
oningof Epi
spa
dias
.
geni
talt
uber
c l
e. WhenyouhaveEpispa
dia
s,y
ouhityurEy
o e
whenyoupEE.
Des
centoft
est
esandov
ari
es
D
ESC
RIP
TIO
N mA
lER
EmN
ANT F
EmA
lER
EmN
ANT
Guber
nac
ulum Ba
ndo
ffibr
oust
is
sue
. Anc ho rst este swi thins cr ot
um. Ovar
ianl
igament+round
The round ligament of the uterus can cause normal pain during pregnancy. l
iga
m entofut
erus
.
Pr
oces
susva
gina
lis Ev
agi
nat
iono
fpe
rit
one
um. For
mst
uni
cav
agi
nal
is
. Obl
it
era
ted.
Failure of processus vaginalis to close can lead to an indirect inguinal hernia.
R
EPROD
UCT
IVE
—ANA
TOmy
Gonadal
drai
nage
Venousdr
ainage Leftovar
y/t
esti
s l eftgonada
lve i
n l e
ftrena Le
l “ f
tgona
dalv
eint
ake
stheLongestwa y.
”
vein I VC.
In males, varicoceles are more common I
VC
on the left, but in women, ovarian vein
Ri
g htovary
/tes
tis rightgonadalvei
n I VC.
thrombosis is more common on the right Becausethelefts
permaticvei
ne nte
rsthelef
t
since the right ovarian vein drains directly
into the IVC, just like the right testicular vein. r
e nalve
ina ta90°ang l
e,fowislessl
ami nar
Nutcracker Syndrome - Compression of the onleftt
ha nonr i
ght l eftv
enousp r
essure
left renal vein between the abdominal aorta
and superior mesenteric artery, causing >r i
ghtvenouspress
ure v a
ric
oc el
emo re
a varicocele. L
eft
ren
alv
ein
commo nont heleft
.
Gon
ada
lve
ins
L
ymphat
icdr
aina
ge Ovari
es/
tes t
es par
a -a
orti
cl ymp hnodes.
These are outside, hence, external iliac. Bodyofute r
us/cer
v i
x/superiorpartofbl
adder

exte
rna lil
iacnode s.
These are inside, hence, internal iliac. Pros
tat
e/cervix/
corpusc avernosum/pro
ximal
vagi
na i
nternalili
acno de s.
These are on the surface, so, superficial.
Dist
alvagina/vulv
a /
scrotum/ dis
tala
nus

superfic
ialinguinalno de s
. P
ampin
if
orm
"The penis goes deep."
Glanspeni s deepi nguina lnodes
. p
lex
us
UWORLD= A 31yo man comes to the ED complaining of right-sided scrotal pain and swelling that has gradually worsened over the last 3 days. His T=101F and
on physical exam, his right hemiscrotum is warm, tender, and erythematous. The cremasteric reflex is present. A scrotal ultrasound reveals a fluid collection consistent
with a superficial scrotal abscess. What lymph node group is most likely to be tender and swollen? Superficial inguinal (71%) but 23% chose Para-aortic. Lymph
drainage of the scrotum is via the superficial inguinal lymph nodes, which drain nearly all cutaneous lymph from the umbilicus to the feet, including external genitalia
and anus up to the dentate line. More is on page 97, where they discuss the only exception is the popliteal drainage for skin below the umbilicus.
Prostate cancer spreads via the prostatic venous plexus, which goes to the vertebral venous plexus and runs up the entire spinal column to connect with the brain via a valveless system, allowing
bidirectional flow to regulate incracranial pressure. This explains the propensity of tumors to metastasize to the brain and why prostate cancer can metastasize to the lower back.
A 23yo man comes to the physician complaining of right-sided testicular swelling. He first noticed the swelling 1 week ago while getting ready for work. He denies any testicular pain or history of
trauma. However, he has noticed a heavy, pressing sensation involving his scrotum and lower abdomen. Physical exam reveals asymmetric swelling of the right testis, and subsequent
ultrasonography shows a solid testicular mass. If malignant, this patient's tumor is most likely to spread to which lymph node group? Para-aortic. In general, the lymph drainage from an organ
follows the path of the arterial supply to that site. During fetal development, the testes originate within the retroperitoneum and establish their arterial supply from the adbominal aorta, so lymph
from the testes drains through lymph channels directly back to the para-aortic, retroperitoneal lymph nodes.
RepRoduct ive R EPR
ODUC
TIVE
—ANA
TOmy S
ecti oNi i
i 6
11
UWORLD= A 24yo woman at 38 weeks gestation delivers healthy twins vaginally after a prolonged labor. Shortly after the placenta is delivered,
profuse vaginal bleeding and a boggy uterus are noted on exam. Uterine massage and uterotonic medications, including oxytocin, fail to stop the
bleeding. The patient is taken for laparotomy. Bilateral ligation of which artery will control her bleeding and preserve her fertility? Internal iliac.
Postpartum hermorrhage is an obstetrical emergency and a leading cause of maternal mortality. The pelvic organs are mainly supplied by the
internal iliac arteries, also known as the hypogastric arteries. Other organs have collateral blood supply, such as ovaries via ovarian artery.
Femal
erepr
oduc
tiveanat
omy Mes
osal
pi
nx Mes
ovar
iu
m
(
ofb
roa
dli
gament
) (
ofbr
oadl
iga
men
t)
F
al
lop
iant
ube Ovar
ia
n
l
ig
ament Ov
ari
ana
rt
ery
I
nf
und
ibu
lopel
vi
c F
al
lop
iant
ube
Ov
ary
F
und
us
l
iga
me n
t Pouchof Ut
er
us
Dougl
as Round
R
ectu
m li
gament
of
uter
us
F
imb
ri
ae B
lad
der
Ov
ary E
ndo
met
ri
um
Me
sometr
ium My
ome
tr
iu
m
(ofbr
oad
li
gament
) Ca
rdi
nal
li
game
nt
Ure
ter
Ut
er
osac
ral F
orn
ix
li
gament Ce
rvi
x Os V
agi
na Ur
et
hra
V
agi
na
P
ost
eri
orv
iew S
agi
t
tal
vie
w
l
IgA
mEN
T C
ONN
ECT
S S
TRUC
TUR
ESC
ONT
AIN
ED N
OTE
S
I
nfundibul
ope
lvi
c Ovar
iest
olat
era
l Ov
ari
anv
ess
els Al
socall
edsuspensor
yl ig
amentoft
heovary.
li
ga ment p
elvi
cwa l
l Li
gat
ev es
sel
sduringoo phor
ect
omytoavoid
b
leedi
ng .
Ur
ete
rc ours
esret
roper
itoneal
ly
,cl
oset
og onada
l
v
ess
e l
s a
tris
kofinjuryduri
ngli
gat
ionof
o
varia
nv es
sel
s.
Cardinal
(tr
ansv
ers
e Cer
vixtos
idewa
llof Ut
eri
nev
ess
els Ur
ete
ra tr
is
kofinj
uryd
uri
ngl
iga
ti
ono
fut
eri
ne
cervi
cal
)li
gament p
elvi
s v
ess
elsinhys
ter
ect
omy.
Roundl
iga
mentoft
he Ut
eri
neho r
nt ol abia De r
iva
tiv
eofgube
rnacul
um.Tr
ave
lsthrough
ut
erus maj
ora Round ligament pain is a sharp pain felt in the lower roundingui
nalcana
l;a
bov
etheart
eryo f
groin area during pregnancy. This is normal. Sampson.
Br
oadl
iga
ment Ut
e r
us,
fal
lopi
ant
ubes, Ovar
ies
,fal
lopi
an Fol
dofperi
tone
um tha
tcomp
rise
sthe
a
ndo var
iest
ope
lvi
c t
ubes,
round mesos
alp
inx,mes
ome t
ri
um,andmesov
ari
um.
s
idewall l
iga
me nt
sofuter
us
Ova
ria
nli
gament Media
lpol
eofov
aryt
o De
riv
ati
veofguber
nacul
um.
ut
eri
nehor
n Ov
ari
anlig
ame ntl
at
chest
ola
ter
alut
erus
.
Oophorectomy (due to ovarian mass) -- Suspensory Infundibulopelvic ligament. Hysterectomy (due to endoemtrial cancer or fibroids) -- Cardinal transverse cervical ligament.
Adnexal(
ovar
ian) Twis
tingofovaryandfallo
piant
ub earoundinfundi
bulopel
vicl
igamentandovar
ianlig
ame nt
tor
sion
compre s
si
onofov ari
anvess
elsininfundi
bulope
lvi
cl i
gament blocka
geoflymphati
ca nd
ve
no usoutfow.Continuedart
eria
lpe r
fusi
on ov
ari
ane dema c
o mplet
eblo
ckageofarteri
al
i
nfo w necr
osi
s,localhemorrhage
.
Ass
ociat
edwi t
hova r
ianma ss
es.Pres
entswit
ha cut
epelvi
cpa i
n,adnexalmass
,nause
a/vomiting
.
UWORLD= A 28yo woman, g1p0, goes into labor at 38 weeks

gestation. During the second stage, as the patient is pushing, the
fetus develops a non-reassuring fetal heart rate. A midline
episiotomy is performed to expedite delivery. A vertical, midline
incision is made at the posterior vaginal opening through the
vaginal and subvaginal mucosa. Which structure is most likely
involved in this incision?
Perineal body. It is essential to the integrity of the pelvic floor and
cut in a midline episiotomy. A midline episiotomy is a vertical
incision from the posterior vaginal wall to the perineal body.
6
ve R E
P ROD UC
TIVE
—ANA TOmy
UWORLD = A 33yo nulligravid woman comes to the office for evaluation of infertility. She has never been pregnant despite years of unprotected intercourse with her husband. She also has pelvic
pain, which worsens with menses. The pain has persisted despite medical therapy and is suspected to be due to endometriosis. Laparoscopy is performed and multiple flesh-colored nodules are
present on the pelvic organs, along with thin, firmy adhesions. In addition to having endometrial glands with hemosiderin pigment, one biopsy contains simple cuboidal epithelial cells. What is the
most likely site of that biopsy? Ovary. Its the only part of the female reproductive epithelial histology with simple cuboidal cells, because it breaks and heals monthly.
Femalerepr
oducti
ve T
IS
SUE H
IST
OlO
gy/
NOT
ES
epi
theli
alhi
stol
ogy Vul
va The outer portions are squamous because St
rat
ifie
dsq
uamouse
pit
hel
ium
A Va
gina they shed often due to sex and bathing. St
rat
ifie
dsq
uamouse
pit
hel
ium,
nonk
era
tini
zed
Ec
toc
erv
ix St
rat
ifie
dsq
uamouse
pit
hel
ium,
nonk
era
tini
zed
Tr
ans
for
mat
ionz
one Sq
uamoco
lumnarjunct
ionA (
mos
tcommon
The inner portions are columnar to secrete mucous. a
reaf
orc
ervi
calc
a nc
er)
End
oce
rvi
x Si
mpl
ecol
umna
repi
the
lium
Ut
erus Si
mplecolumnarepit
hel
ium wi
thlongt
ubul
ar
Remember that the transformation zone has squamocolumnar epithelium, so outside that its squamous, and gl
andsinpro
lif
era
tiv
ephase
;coil
edgla
ndsi
n
inside that its columnar. The ovary is the only one with simple cuboidal epithelium, and the cells divide and
proliferate rapidly to repair the ovarian surface defects from ovulation. s
ecret
oryphas
e
Fa
ll
opi
ant
ube Si
mpl
ecol
umna
repi
the
lium,
cil
ia
ted
Ov
ary
,out
ers
urf
ace Si
mpl ec
uboidalepit
heli
um (g
ermina
l
epi
thel
ium cove
ringsurf
aceofov
ary
)
Mal
erepr
oduc
tiv
eanat
omy
Ur
et
er
B
lad
der S
emi
nal
ves
ic
le
V
asd
efe
ren
s A
mpul
la
E
jac
ula
tor
ydu
ct He
ado
fep
idi
dymi
s
S
ymp
hys
isp
ubi
s S
ept
a
P
ros
tat
e E
ff
ere
ntd
uct
ul
e
B
ulbou
ret
hra
l R
etet
est
i
s
Ur
et
hr
a
g
lan
d(Cowper
)
Co
rpu
sca
ver
nos
um
E
pid
idy
mis S
emi
ni
fer
ous V
asd
efe
ren
s
t
ubul
es
P
rep
uce
T
unic
a
Gl
ans a
lbu
gin
ea
T
est
i
s
S
cro
tum
T
ai
lof
epi
di
dymi
s
Pathwayo fs
pe rm dur
inge
jac
ula
ti
on—
SEVEN UP:
Semi ni
fer
o ustubul
es
Epididymis
Vasde f
erens
Ejaculat
oryduc t
s
(Nothing)
Urethra
Penis
UWORLD= A 62yo man comes to the office due to an elevated PSA level on a screening test. When asked about
genitourinary symptoms, the patient says, "It often takes a bit of time before my urine starts flowing," but he has no
other problems. Abdominal and external genital exam are unremarkable. Digital rectal exam reveals hard prostate
nodules. A biopsy confirms adenocarcinoma, and the patient undergoes a radical prostatectomy. During the
surgery, the nerves within the fascia surrounding the gland are inadvertently injured. What is the most likely
consequence of the nerve injury? The picture to the left came with this explanation.
Erectile dysfunction. The prostatic plexus lies within the fascia of the prostate and
originates from the inferior hypogastric plexus. The lesser and greater cavernous nerves arise from the prostatic
plexus and pass beneath the pubic arch to innervate the corpora cavernosa of the penis and urethra. The
cavernous nerves carry post-ganglionic parasympathetic fibers that facilitate penile erection. Prostatectomy or
injury to the prostatic plexus can cause erectile dysfunction, so surgeons attempt to preserve the integrity of the
prostatic fascial shell during surgery.
Branches of the pudendal nerve innervate the external urethral and anal sphincters. Pudendal injury can lead to
fecal incontinence, decreased penile sensation, or external urethral sphincter paralysis. The cremasteric reflex is
elicited by lightly stroking the medial thigh, which causes contraction of the cremaster muscle to pull up the
ipsilateral testis. This reflex is mediated by the genitofemoral nerve of L1-L2 and may be injured with
testicular torsion or L1-L2 spinal injury.
RepRoduct ive R EPR
ODUC
TIVE
—ANA
TOmy S
ecti oNi i
i 6
13
Ur
ethr
ali
njur
y Occur
salmostexc
lusi
vel
yinmen.Suspectifb
loo
ds ee
na turethr
alme at
us.Ur
ethr
al
ca
thet
eri
zat
ionisrel
ati
vel
yco
ntr
aindic
ated.
Ant
eri
orurethrali
njury Post
eriorurethr
alinj
ury
P
ARTO
FUR
ETH
RA Bul
bar(s
pongy)ure
thra Memb ranousuret
hra
mE
CHA
NIS
m Pe
rine
als
tra
ddl
einj
ury Pe
lvi
cfr
act
ure
l
OCA
TIO
NO FURI
NEl
EAK
/bl
OOD Bloodaccumula
tesi
nscro
tum Ur
inel
eaksi
ntor
etr
opub
ics
pac
e
A
CCU
mU l
ATIO
N IfBuckfa
sciai
stor
n,ur
inees
cape
sint
ope
rine
al
s
pace
P
RES
ENT
ATI
ON Bl
ooda
tur
ethr
alme
atusa
nds
crot
alhe
mat
oma Bl
oodature
thr
alme
atusa
ndhi
gh-
ri
ding
p
rost
ate
The retropubic space is the extraperitoneal space
between the pubic symphysis and the urinary R
etr
opubi
c
bladder. Buck's fascia is a layer of deep fascia
covering the three erectile bodies of the penis, and
sp
ace
it has the deep dorsal vein of the penis inside it.
De
eppenil
e Bloo
dy
(
Buck
)fa
sci
a e
xtr
ava
sat
ion
T
orni
nte
rmedi
at
e
p
arto
fure
thr
a
P
erf
ora
ti
onofs
pongyur
et
hra Membr
anou
s
(
ru
ptur
eofB
uckfa
sci
a) ur
et
hra
Autonomi c Er
e ct
ion—Pa rasympatheti
cne rv
ouss y
stem Poi
nt,Sque
eze,andShoot
.
i
nner va
t i
onofmal
e (
pelvicspla
nc hnicnerves
,S2-S4 )
: PDE-5inhi
bit
ors(e
g,s
il
denafil
) c
GMP
sexualrespons
e NO cGMP s moo t
hmus cl
e br
eakdown.
r
e l
axati
on v a
sodil
ati
on pr oerect
il
e.
No r
epinephrine [
Ca 2+
]in s moo t
h
mus c
leco ntr
acti
on v as
oc onst
ric
tio
n
anti
e r
ec t
il
e.
Emissi
on—Sy mpa t
heti
cne r
vouss ys
tem
(
hy pogast
ri
cne rve,T11-
L2 )
.
Expulsi
on—v iscera
landSo ma t
icne r
ves
(
pud endalne r
ve).
The rectus abdominis is a pair of vertically aligned muscles that connect the xiphoid process to the pubic symphysis. The
arcuate line is a horizontal line below the umbilicus that demarcates the lower limit of the posterior rectus sheath. Above
the arcuate line, the rectus abdominis is surrounded by anterior and posterior sheaths; below, the muscle is only covered
by the anterior sheath. The superior and inferior epigastric arteries (braches of the iliac artery) supply the superior and
inferior portions of the rectus abdominis muscle, respectively. The epigastric artery ascends the psoterior surface of the
rectus abdominis muscle and enters the lateral aspect of this muscle at the arcuate line. Because there is no supporting
posterior sheat, trauma to the inferior epigastric artery below the arcuate line can result in significant hemorrhage.
6
ve R E
P ROD UC
TIVE
—ANA TOmy
Semi
nif
eroust
ubul
es
C
Ell F
UNC
TIO
N l
OCA
TIO
N/N
OTE
S
Sper
mat
ogoni
a Maint
ainger
mc el
lpoola
ndpr
oduc
e1° Li
nese
minife
roust
ubul
esA
s
permato
cytes
. Germcel
ls
Ser
tol
icel
ls Sec r
e t
ei nhibinB i nhi
bitFSH. Li
neseminif
eroustubules
Sec r
e t
ea ndr ogen-bi
ndingpr otei
n ma int
ain Non-ge
rmc el
ls
loca llevelsoftest
oster
one. Conver
tte
stost
eroneanda ndr
ost
enedi
oneto
Prod uceMI F. es
tr
ogensviaaromatase
Tightj unc ti
onsbe tweenadja ce
ntSert
olicel
ls Se
rtol
icel
lsSuppo tSp
r erm Synt
hes
isand
form bl ood- t
est
isb a
rri
er i sol
atega
me tes i
nhi tFSH
bi
from a uto i
mmunea t
tac
k. Homo l
ogoffema l
egranulos
acel
ls
Suppo r
ta ndnour is
hde velopingsper
ma toz
oa .
Re gulates perma t
ogenesi
s.
Tempe raturesensit
ive;s permp r
oduct
iona nd t
emperat
urese
eni
nva
ric
oce
le,
inhibinBwi t
h t empe r
a tur
e. c
rypt
orc
hidi
sm
L
eydi
gcel
ls Se
creet
t estost
eronei
nthepres
enceofLH; Int
ers
ti
ti
um
t
est
ost
eroneproduct
ionuna
ffe
cte
dby Endocri
nec e
lls
t
emperature
. Homo l
ogo ff
ema l
ethe
caint
ernac
ell
s
Leydi
es(la
die)di
s gtes
tos
ter
one
HYPOT
HAL
AMUS
Gn
RH
FSH --> Sertoli cells --> Inhibin B --> (-) FSH

Lh --> Leydig cells --> Testosterone --> (-) LH and (-) GnRH
Anter
ior
pi
tuit
ary
S
per
mat
ogoni
um
I
nhi
bi
nB S
per
mat
ocy
te
S
per
mat
ids
F
SH S
ert
oli
cel
l
L
H S
per
mat
ozoon
A
L
eydi
gcel
l
An
droge
n-
bi
ndi
ngpro
tei
n
T
est
ost
eron
e
Ca
pil
l
ary
S
ertol
icel
l
nucl
eus
Lumenof
s
emi
nif
eroust
ubul
e
S
PERMAT
OGENES
IS
RepRoduct ive R EPROD
UCT
IVE
—P Hy
SI Ogy S
Ol ecti oNi i
i 6
15
R
EPRODUC
TIVE
—PHy
SIOl
Ogy
Sper
mat
ogenes
is Be
ginsatpubertywit
hs perma t
ogonia
.Full Goni
“ sg
um”i oi
ngtobeas
per
m;Zo
“ o
n”i
s
d
evelopmenttakes2mo nths.Occursin “Zo
oming
”toegg
.
s
eminifer
oustubule
s. Pr
od ucess
permati
ds
t
hatundergospermiogenesis(
los
sof
c
ytoplas
micc ont
ents,gai
nofa cr
osomalcap)
t
oform ma t
uresper
ma t
ozoa.
N=pl
oi
dy
C=#ofc
hroma
ti
ds
S
per
mio
gen
esi
s
S
per
ma t
ogoni
um 1
°sp
ermat
ocy
te 2
°sp
ermato
cyt
e S
perma t
i
d Ma
tur
esper
matoz
oon
Di
ploi
d Dipl
oi
d Hapl
oid Ha p
loid Hapl
oid
(2N,2C) (
2N,4C) (
1N,2C) (1N,1C) (1
N,1C)
S
per
m
23 A
cro
some T
ai
l
si
ngl
e
2 3 (
sex
=X) He
ad
s
is
ter Nu
cle
us
B
loo
d-t
est
i
s c
hromat
ids
bar
ri
er (
sex=X-X
) Ne
ck
23
si
ngl
e
Mi
ddle
n
46 46 (
sex
=X)
o
i
pi
ece
t
si
ngl
e si
st
er
n
uc
chr
omo- c
hromati
ds
t
hj
s
omes
( =X-X
)
g
sex
i
T
(
se
x=X-Y) Y-Y 23 Not
e:I
mpair
edtai
lmobi
li
t
ycanl
eadt
o
si
ngl
e i
nf
ert
il
i
ty(s
eeninci
l
iar
y
23 (
sex
=Y) dy
ski
nesi
a/
Kart
agene
rsyn
dro
me).
s
is
ter
c
hromat
ids
(s
ex=Y-Y
) 23
si
ngl
e
Repl
i
cat
i
on
Me
ios
isI
I (
se
x=Y)
(
in
ter
phas
e) Me
ios
isI
The events inside the nucleus are the same for males and females, but the division of the cytoplasm is different in both genders.
Spermatogonia/oogonia (Gonia) are somatic cells, not gametes, so they divide by mitosis until they enter meiosis, and this point is different in both genders.
Now they become Spermatocytes or oocytes and enter the first meiotic division.
The first thing that occurs is the replication of DNA, thus, doubling the amount of DNA we had 2n-->4n. Initially, we had 1 pair of chromosomes as a 2n cell, and now we have
a 4n cell because each chromosome has 2 strands/chromatids. It is still 46 chromosomes, its just that now they are double stranded.
At the secondary spermatocyte point, we have 2 cells each having 1 chromosome from each pair. So now we have 23 chromosomes that are double stranded, so 23 1n 2c.
There are half as many chromsomes but twice as many DNA in each of the secondary spermatocytes/oocytes.
In males, meiosis 1 does not start until puberty. So before puberty, there is no meiotic activity in the male gonads.
This meiosis then happens from puberty until the day of death, continuously.
In females, the formation of primary oocytes begins around the 5th month of development. By the time of birth, all the oogonia have either differentiated into primary oocytes or have died.
So in the newborn female, there are no oogonia. Meiosis is halted at Prophase 1 until after puberty.
Each month after puberty, 1 of the primary oocytes will continue the meiosis and become secondary oocyte and halt at Metaphase 2, which is then ovulated.
It will remain halted until menstruation ends or fertilization.
In the second meiotic division, we get 4 cells and each has 1 chromatid, making it 23 1n 1c, the definitive gametes.
In males, we end up with 4 sperm cells.
In females, the primary oocyte divides its cytoplasm unequally, so almost all the cytoplasm goes to 1 cell, which is denoted the secondary oocyte. The others with lesser cytoplasm are
called polar bodies and those die. So in females, there is 1 secondary spermatocyte, which divides again in meiosis 2, once again giving unequal cytoplasm so that only 1 gamete is
formed and a 2nd polar body is made. That 1 gamete will become the ovum.
6
ve R E
P ROD UC
TIVE
—P HySI
OlOgy
Being 2 is better than being alone.

Es
trogen Pregnancy has three and a pregnant woman is most
susceptible.
S
OUR
CE Ovar
y(1
7β-est
radi
ol)
,pla
centa(
estr
iol
),a
dipos
e Pot
enc
y:e
str
a ol>e
di str
one>e
str
iol
.
t
is
sue(
est
ronev i
aaromati
zat
ion
).
F
UNC
TION Devel
opme ntofgenital
iaandbr ea
st,f
ema l
efat Pr
egna nc y:
Fetal placental aromatase deficiency
di
str
ibution. 5 0-fold inestr
adiolandes
tr
one
presents with ambiguous genitalia in the Growtho ffol
licl
e,endo metria
lprol
ife
rati
on, 1 000- f
old inestr
iol(
indi
cat
oroff
etalwe
ll-
female infant and virilization of the
mother since aromatase cannot convert my ome t
r i
alexcit
abil
ity. b eing )
androstenedione to estrone and
testosterone to estradiol, causing those
Upreg
ulatio
no fest
rog e
n, LH, a
ndprogest
ero
ne Es
troge nrecept
orsexpr
e s
sedi
nc y
topl
asm;
hormones to accumulate. Aromatase re
ceptor
s;feedbackinhibit
ionofFSHa nd t
ransloc a
tetonucle
uswhe nboundby
converts testosterone to estradiol in the
adrenal zona reticularis (page 341). LH,thenLHs urge;st
imulatio
no fp
rolac
ti
n es
troge n.
se
cret
ion.
tr
ansportprotei
ns ,SHBG; HDL; LDL.
L
H Ch
ole
ste
rol
L
HR
Ch
ole
ste
rol
T
hec
ace
ll
s Gr
anu
los
ace
ll
s c
AMP De
smo
las
e <--- Analogous to male
Leydig cells.
T
hec
acel
l A
ndr
ost
ene
dio
ne
Gr
anu
los
ace
ll A
ndr
ost
ene
dio
ne
A
roma
tas
e
E
str
one
c
AMP <--- Analogous to male
E
str
adi
ol Sertoli cells.
F
SHR
F
oll
i
cle E
str
oge
n
F
SH
Pr
oges
ter
one
S
OUR
CE Cor
pusluteum, pl
acenta,adrenalcor
tex
,tes
tes
. Fa
lli
npr oges
ter
onea f
terdel
iver
ydis
inhibi
ts
F
UNC
TION Duri
nglutealphas
e,pr epar
esuterusf
or pr
ola
cti
n l
acta
tion. pr
o g
est
ero
n eis
i
mplanta
tionoffert
il
iz edegg: i
ndic
ati
v eofovula
tio
n.
Sti
mul a
tionofend ome t
rialg
landula
r Pr
ogest
erone i
spro-ges
tat
ion.
secr
eti
onsa ndspi
ra lart
erydevel
opme nt Pr
olact
in i
spro-l
actat
ion.
Prod uc t
ionoft hic
kc ervi
calmuc us

inhi b i
tssperme ntryintouterus
Preve ntionofe ndome tr
ialhyperplasi
a
b odyt e
mpe r
ature
e st
r ogenre cepto
re xpr
e s
sion
g ona dotropin(LH, FSH)s ecretio
n
Dur
ingpr egnanc y:
Ma inte nanceo fpregnancy
my ome t
ri
a lexci
tabil
it
y contrac
tion
fr
eq ue ncyandi ntensi
ty
p rolac t
inac t
iononb reasts
UWORLD= A 35yo Caucasian primigravida is found to have gallstones at 38 weeks of an uncomplicated pregnancy. Ultrasonography performed one year ago failed to demonstrate any
abnormalities. What pathogenetic components most likely contributed to her condition? Estrogen-induced cholesterol hypersecretion and progesterone-induced gallbladder hypomotility.
Pregnancy and the use of OCPs predispose to gallstone formation. Estrogenic influence increases cholesterol synthesis by upregulating HMG-CoA reductase activity, which causes the bile to
become supersaturated with cholesterol. Progesterone reduces bile acid secretion and slows gallbladder emptying.
UCT
IVE
—P Hy
SI Ogy S
Ol ecti oNi i
i 6
17
Oogenes
is 1
°ooc
yte
sbe
ginme
ios
isIdur
ingf
eta
lli
fea
ndc
omp
let
eme
ios
isIj
ustpr
iort
oov
ula
tio
n.
Me
ios
isIi
sar
res
tedi Opha
npr seIf
ory
ear
sunt
ilOv
ula
ti
on(
1°ooc
yte
s).
Me
ios
isI
Iisa
rre
ste
dinme
tapha
seI
Iunt
ilf
ert
il
iza
tion(
2°ooc
yte
s).
“Ane
ggme
tas
per
m.”
I
ffe
rti
li
zat
iondoe
snoto
ccurwi
thi
n1da
y,t
he2°ooc
ytede
gene
rat
es.
N=pl
oi
dy
C=#ofc
hroma
ti
ds
Oogoni
um 1
°oocyt
e 2
°oocyt
e Ovum
Di
p l
oi
d Dip
loi
d Hapl
oid Ha p
loid
(
2N,2C) (
2N,4C) (1
N,2C) (
1 N,1C)
Ar
res
tedin A
rre
ste
din
pr
ophaseI meta
phaseI
I
u
nti
lovu
lati
on u
nti
lfe
rt
il
iz
ati
on
23
si
ngl
e
c
hro
mati
ds
2 3
s
is
ter Ov
um
c
hromat
ids
46 4 6 P
ola
rbo
dy
si
ngl
e s
is
ter
c
hro
mosome
s c
hromat
ids
P
ola
rbo
dy
P
olarbody
(
candegene
rat
e
o
rg i
veri
set
o2
p
olarbodi
es) P
ola
rbo
dy
Repl
i
cat
ion Me
ios
isI Me
ios
isI
I
(
in
ter
phas
e)
Ovul
ati
on es
troge
n, GnRHr ecept
orsona nt
eri
or —t ra
nsientmid-cy
cleovul
ator
y
p
itui
tar
y.Est
rogensurg
ethe nst
imulatesLH pa
in(“Middl
ehur t
s”)
;c l
ass
ica
ll
ya ss
oci
at
ed
r
elea
se o vula
tion(r
uptureoffoll
icl
e)
. wi
thperi
tonea
lirr
ita
tion(eg,f
oll
icul
ar
t
empe r
atur
e(proges
ter
oneinduc ed
). s
well
ing/
rupt
ure,fa
llopia
ntubec ont
rac
tio
n).
Canmimi ca
ppend i
citi
s.
6
ve R E
P ROD UC
TIVE
—P HySI
OlOgy
Mens
trual
cyc
le Foll
icul
arpha s
ecanv a
ryinlength. Lute
alphas
eis14day
s.Ovula
tio y+1
nda 4da
ys=
me nst
ruati
on.
Foll
icul
arg r
owthisfas
tes
tduring2 ndwe ekoft
hefol
li
cul
arphas
e.
Estr
ogens ti
mulat
esendometr
ia lproli
fer
ati
on.
Progest
eronema i
nta
insendome tri
um tosuppor
timpla
nta
tio
n.
progest
e r
one f
ert
ili
ty
.
PHAS
ESOFOVARI
ANCYCL
E: F
OLL
ICUL
ARPHAS
E L
UTE
ALP
HAS
E
L
H
F
SH
Hy
pot
hal
amu
s An
ter
ior
Gn
RH p
it
uit
ar
y L
H F
SH
on
es
i
t
t
a
l
a
mu
ul
ti
Ov
S
P
ri
mordi
al De
vel
oping Cor
pus Cor
pus
fol
l
icl
es fol
l
icl
e l
ut
eum a
lbi
can
s
Ov
ary
P
rod
uce
s
Normal proliferative endometrium consists of uniform, nonbranching,

s
e
nonbudding glands evenly distributed throughout a uniform stroma.

r
Pou
dc
In the midproliferative phase, the glands are tubular, narrow, and lined P
rog
est
eron
e
with pseudostratified, elongated, mitotically active epithelial cells and
a stratum functionale layer with compact, nonedematous stroma.
Ovulation is at the late-proliferative phase, which has coiled glands and

E
str
oge
n
occasional cytoplasmic vacuoles in the glandular epithelium. The body temperature
also rises 1C at
In the secretory phase, glands acquire large cytoplasmic vacuoles that ovulation.
release glycogen-rich mucus and the stroma becomes edematous with
prominent spiral arteries extending to the endometrial surface.
E
ndome
tri
um
n
PHAS
ESOFUT
ERI
NECYCL
E: Me
nse
s P
rol
i
fer
ati
ve S
ecr
eto
ry Me
nse
s
u
Ovlt
ao
i
UWORLD= A 27yo woman comes to the office for evaluation of fertility difficulties after 3 elective first-trimester abortions in her late teens and use of OCPs since age 22. She is not having any
periods even though she stopped contraception a year ago. Her TSH, FSH, LH, prolactin, and bhCG are normal. As part of her evalution for amenorrhea, 10 days of oral medroxyprogesterone
is administered. A few days after completing her progesterone course, the patient has moderately heavy bleeding with some cramping. What endometrial process caused the bleeding?
Apoptosis. Progesterone secretion in the luteal phase transforms the endometrium from proliferative to secretory so implantation can occur. Exogenous intake of progesterone for about 10 days
also matures the endometrial lining. When the endometrium is no longer exposed to progesterone (like in this progesterone withdrawal test), prostaglandin production increases, leading to
vasoconstriction of the spiral arteries. Progesterone withdrawal increases metallopreotease secretion by endometrial stromal cells, degrading the extracellular matrix, leading to apoptosis of the
endometrial epithelium. The net effect is degeneration of the functionalis layer, which sloughs away as menstrual flow.
A 14yo girl is brought in for routine checkup. When asked about her periods, she says that she does not get them every month. When she does have her period, she bleeds for 7-10 days and
needs to use nearly twice as many tampons a day as her older sister. She also complains of occasional spotting that happens outside of her normal periods. The patient underwent menarche
last year and her last period was 6 weeks ago. She eats well, exercises, has nothing in her past medical history, and her BMI is 25. What is the most likely cause of her complaints?
Anovulatory cycles. In most women age 20-40 years, periods are consistent and last 24-35 days, with menstrual flow ranging from 4-6 days. However, adolescents typically have an immature
hypothalamic-pituitary-ovarian axis for several years following menarche. During this time, they may have longer periods and irregular bleeding due to anovulatory cycles. In the absence of
ovulation, the ovarian follicle does not degenerate and become a corpus luteum, so no progesterone is produced and estrogen remains persistently high, causing the endometrium to remain in
the proliferative phase. When the period finally does happen, it will be more than usual; heavy bleeding.
UCT
IVE
—P Hy
SI Ogy S
Ol ecti oNi i
i 6
19
Abnor
malut
eri
ne Char
ac t
erizeda se i
therheavyme nst
rual Te
rmssuchasdys
func
tio
nalut
eri
neb
leedi
ng,
bl
eedi
ng bl
eeding( AUB/ HMB)ori nt e
rme nst
rual menor
rhag
ia,o
lig
omenorr
heaar
enolo
nger
bl
eeding( AUB/ IMB) . r
ecommended.
Thes
ea refurthe rsubcat
e g
orizedbyPALM-
COEI N:
Structuralc auses(PALM) :Po l
yp,
Ade nomy os i
s,Le i
omy oma ,orMa li
gnancy
/
hype r
pla s
ia
No n-st
ruc turalcauses(COEI N):
Coa gulopa thy,Ov ul
atory,Endo metr
ial
,
Iatr
o genic,No ty e
tclas
sified
Pr
egnanc
y Fert
ilizat
ionmo stc o mmo nlyoc cursi nuppe r
m
s
u
e
e
e
c
endoff a l
lo pia nt ube( t
hea mpul l
a).Oc cur s
t
n
r
n
u
mo
u
sl
a
o
i
t
o
t
i
ns
n
or
within1 da yo fo vula t
ion.
u
s
e
p
n
i
c
Cor
h
a
Ma
a
Huma np l
acental
r
l
Implantationwi thint hewa llo fthe
T
P
lac
to gen
uteruso cc urs6da y safterfertil
iz ation. Prolacti
n
l
Prog e
s t
erone
e
Sync yti
otrop ho blastss ecret
ehCG, whi chi s
elv
e
detectablei nbl ood1we eka fterc onc eption
mon
Est
r ogens
ando nho met estinur ine2 we e k
sa ft
e r r
Ho
conc epti
on.
Gestationala ge—c a lculatedfro m da teofla st hCG
me nstrualpe riod.
7 1 4 2 1 2 8 3 5 4 2
Embr yonica g e—c alc ulat
e dfrom da teof We ek sof pr
egna ncy
conc epti
on( gestatio nala gemi nus2we ek s)
.
Pl ac ent a lho rmo nes ec re ti
o ng e nerallyinc rea s
e s
Physiol
o gica da pt at
ionsi np regna nc y:
ov e rthec our seofpr e gna nc y,b uthCG pe aksa t
cardiaco ut put( preload, afterload,
8– 10we e ks.
Wikipedia- Distribution of gestational age at HR plac ent alandut e ruspe rfusi
o n)
childbirth among singleton live births, given both
when gestational age is estimated by first Ane mi a( plasma , RBCs )
Gestational age is measured from the first day of the last menstrual cycle.
trimester ultrasound and directly by last Hy perc oa gul ability(to bloodl o ssa t So if your last period started on 4-14-18, your embryonic age is 4-28-18, which
menstrual period. The overlap is pretty good. gives the actual age of the baby. The embryonic age is also from 4-14-18
delivery) because that is the day the embryo was made.
Hy perve nt il
a ti
o n( eli
mi natef e t
a lCO2) The most common system used among healthcare professionals for predicting
l
ipo l
y sisa ndf a tut i
lizat
ion( duet o the due date is Naegele's rule, which estimates the expected date of delivery
(EDD) by adding a year, subtracting three months, and adding seven days to
ma terna lhy po glyce miaa ndi nsul i
n the first day of a woman's last menstrual period (LMP) or corresponding date
resi
s t
anc e ) pre servesgluc osea nda mi no as estimated from other means
acidsforut ilizationb ythef etus .
UWORLD= A 34yo woman with PCOS comes to the office with her husband for treatment of infertility.
She has been unable to conceive despite having unprotected sexual intercourse several times a week
for the past 2 years. Her menses are irregular and occur every 2-3 months, consistent with chronic
anovulation. She does not use tobacco, alcohol, or illicit drugs. She takes no medications and has no
allergies. BMI is 32. Phsyical exam shows coarse hair on her chin and abdomen. She is initially
prescribed clomiphene therapy but fails to conceive. She then receives ovulation induction therapy
with a short course of menotropins followed by a single injection of hCG. The use of hCG primarily
mimics what physiologic event? LH surge. Menotropin therapy mimics FSH and triggers the
formation of a dominant ovarian follicle. Exogenous hCG mimics LH because of the alpha subunit.
6
ve R E
P ROD UC
TIVE
—P HySI
OlOgy
Humanc
hor
ioni
cgonadot
ropi
n
S
OUR
CE Sy
ncy
tio
trop
hob
las
tofp
lac
ent
a.
F
UNC
TIO
N Ma intai
nsc o r
pusl ute
um (andthusprogester
one)forfir
st8–10we eksofpr
egnancybyac t
ingli
ke
LH( othe rwisenol utea
lcellst
imulati
on abort
ion).Aft
er8– 1
0we e
ks,pl
acent
asynthesiz
esit
s
owne st
riola ndpr og
ester
onea ndcorpuslut
eum de generat
es.
Use dtode tectpregnancybe ca
us ei
tappearsearl
yinur i
ne( s
eeabo v
e).
Ha sident
ic alαs ubunitasLH, FSH,TSH( sta
tesof hCG c anc ausehypert
hyroi
dis
m).βs ubunit
isunique( p regnancytest
sd e
tectβ
subunit)
.hCG is in mult
ipl
e gest
ati
ons,hy
dati
difor
m
mo l
es,cho r
io c
a r
cinomas,andDo wns yndrome;hCGi s i
ne ct
opic/
fai
li
ngp r
egnancy,Edwa r
ds
syndrome , andPa tausyndrome .
Humanpl
acent
al Al
sok
nowna
scho
rioni
cso
mat
oma
mmot
rop
in.
l
act
ogen The average levels of hPL rise with increasing gestational age, so screening for gestational diabetes is most accurate in the third trimester.
S
OUR
CE Sy
ncy
tio
trop
hobl
astofp
lac
ent
a.
F
UNC
TION St
imul
ate
sinsul
inprod
uct
ion;o
ve r
all i
nsul
inre
sis
tance
.Gest
ati
onaldia
bet
esc
anoc
curi
f
mat
ernalp
ancrea
ticf
unc
tioncannotov
ercometheins
uli
nre
sis
tanc
e .
Apgars
cor
e
Ass
essmentofne wbornv i
talsi
gnsfollowi ng
S
cor
e2 S
cor
e1 S
cor
e0 del
iver
yv i
aa1 0-pointscal
ee v
aluateda t1
minuteand5mi nutes.Apgarscoreisba s
ed
onAppe ar
anc ,Pul
e s,Gr
e imace,Ac ti
vity,and
Appearance Respi
rati
on.Apg arscores<7r equi
ref ur t
her
P
ink E
xtr
emi
t
iesbl
ue P
aleo
rbl
ue
eva
luati
on.IfApg arscor
er emainslowa tla
ter
P
ul
se ≥1
00bp
m <1
00b
pm Nop
uls
e t
i
l
mepo
ong-te
r
int
s,
m ne
the
ur
r
ol
ei
og
sr
icda
i
skt
ma
hec
ge.
hildwi lldevel
op
Grimace Cr
p
i
u
l
e
l
sa
sa
nd
way
Gr
ima
wea
c
e
kc
so
ry
r Nor
st
i
e
s
mu
po
l
a
n
t
i
s
et
on
o
A
ct
iv
it
y
A
cti
vemo
veme
nt A
rms
,l
egsfle
xed Nomo
veme
nt
Respiration S
tr
ongc
ry S
low,
ir
reg
ula
r Nob
rea
thi
ng
UCT
IVE
—P Hy
SI Ogy S
Ol ecti oNi i
i 6
21
I
nfantandc
hil
d Mil
est
onedat
esarer
ang
esthathav
ebeenappro
ximateda
ndv a
rybysour
ce.
Chi
ldr
ennotme
eti
ng
devel
opment mi
lest
one
sma ynee
dasse
ssmentf
orpot
enti
aldev
elopment
aldel
ay.
A
gE mO
TOR S
OCI
Al V
ERb
Al/
COg
NIT
IVE
I
nfant Pa
rent
s St
art Obs
ervi
ng,
Primitiverefe xesdisappear— Soci
alsmile(by2mo ) Orients—firsttovoi
ce(b y
Mor o( by3 mo )
,rooting(by St r
angeranxie
ty(by6mo) 4 mo ),t
he ntonamea nd
4 mo ),palma r(by6mo )
, Separ
ati
ona nxi
ety(by9mo
) gestures(by9 mo)
Ba bi
ns ki(by1 2 mo) Ob j
ec tperma nenc
e( by9mo )
Posture—l if
tshe adupp r
one(by Oratory—s ays“mama ”a nd
1 mo ),r
o l
lsands it
s(b y6 mo), “dada ”(by1 0mo)
crawls(b y8mo ),s
tands(by
10 mo ),walks(b y12–1 8mo)
Pi
c ks—pa ssestoysha ndt o
ha nd( by6mo ),Pinc ergra
sp
(by1 0 mo )
Pointstoo bjects(by1 2mo )
T
oddl
er Chi
ld Re
ari
ng Wor
king,
Cruises,t
ake sfirs
tst
eps(by Recreat
ion—p a r
all
elpla
y(by Wo r ds—5 0wor dsbya g e2wi th
12 mo ) 2
4– 36 mo) 2-wo rdphr as
es;2 00 +wo rds
Climbss t
airs(b y18mo) Rapp r
ocheme nt—mo vesaway bya g e3
Cube sstac
ke d—numbe r f
rom a ndret
ur nstomo t
her
=a ge( y
r)×3 (
b y24mo ) Language is the most commonly delayed milestone, with a
prevalence of up to 15% at age 2. Children suspicious of
Cutlery—feedss elfwi
thfor
k Realiz
atio
n—c oregender language disorder should undergo further assessment such
as a hearing exam and a speech & language evaluation.
ands poon( by2 0mo ) i
de nti
tyfor
me d(by36mo )
Ki
c ksb al
l(by2 4mo )
Pr
esc
hool Don’
t F
orge
t,t
hey’
res
til
l L
ear
ning!
Drive—t ri
cycle(3whe el
sa t Freedom—c omf or
tabl
yspends La
ngua g
e —1000wor dsbyag
e
3 yr) partofdayawa yf
rom mother 3( 3zeros)
,usescomplet
e
Dra wings—c opi
esli
neo r (by3y r
) s
ente
nce sandpreposi
ti
ons
circl
e,sti
ckfigure(by4y r) Fri
ends—c ooperat
ivepl
ay,has (by4y r
)
De xte
rit
y —hopsono nefoot ima gi
nar
yf r
iends(by4yr
) Le
gends—c antelldet
ail
ed
(by4 y
r),usesbutt
onso r s
tor
ies(by4y r
)
zippers,groomsself(by5y r
)
Lowbi
rthwei
ght Define
da s<2 5
00g.Caus
edbypre
ma t
uri
tyo
rintr
aut
eri
neg
rowt
hres
tri
cti
on(IUGR)
.As
soc
iat
ed
Basically less than 6 pounds. with r
iskofs
udd
e ni
nfa
ntdea
thsyndr
ome(SIDS)a
ndwit
h over
allmorta
lit
y.
- Asymmetric Dimethylarginine
6
ve R E
P ROD UC
TIVE
—P HySI
OlOgy
L
act
ati
on Af
terparturi
tio
na ndd e
liv
eryofpl a
ce nt
a ,ra
pid i nprogester
onedi sinhibi
tsprol
ac t
in i
nitia
tion
oflac
tat
ion.Suc kli
ngi sre
q ui
re dt
oma intai
nmi lkproduc t
iona nde je
cti
on,since ne rve
s
timulati
on o x
y t
ocinandpr ola
c ti
n.
Pr
o l
acti
n—i nducesa ndma intainsl
actationand r eproductiv
ef unc t
ion.
Oxytoci
n—a s
si
stsinmi lklet
do wn;alsopr omotesute
rinec ontr
ac ti
ons.
Br
e a
stmilkisthei dealnutri
tionforinfants<6mo nthsold.Co ntainsma ter
nalimmuno globuli
ns
(
conferr
ingpa ss
iveimmuni ty
;mo stl
yI gA),mac r
opha g
es,lymphoc y
tes.Breas
tmi lkreducesinfant
i
nfecti
onsa ndisa s
sociat
edwi th r i
skf orchi
ldtod evel
opa st
hma ,all
ergi
es,diabetesme l
li
tus,
a
ndobe sit
y.Gui delinesr
ec omme nde xc l
usi
vel
yb re
a st
fedinfantsgetv i
taminD a ndpos s
ibl
yi r
on
s
up pl
eme ntat
ion.
Br
e a
stf
eeding ma t
ernalri
skofbr ea
sta ndov a
riancanc e
ra ndfac i
lit
atesmothe r
-chil
dbo nding.
Menopaus
e Diagnosedb ya me norrhe
af or1 2mo nths. Ho rmo nalc hanges:e st
rogen, FSH, LH
Cyclic and continuous use of e
str
og e
npr od ucti
onduet oa ge-
linked (
nos urge )
, GnRH.
oral contraceptive (OCP) regimen are
not associated with irregular menses or decli
neinnumbe rofovari
anf oll
icl
es.Aver
age Ca usesHAVOCS:Ho tfa s
he s,Atr
ophyo fthe
amenorrhea, and premenopausal patients
who stop taking OCPs should expect
ageatonseti s5 1years(
earli
e rinsmok er
s)
. Va gi
na ,Os teopor
osi,Co
s rona r
yarterydis
e a
se,
spontaneous return of menses. OCPs Usuall
yp r
ece dedby4– 5ye ar
so fabnorma l Sleepdi sturbances.
may mask vasomotor symptoms that are
typical of menopausal transition, me ns
trualcy cles.Sourc
eo fe st
rogen(est
rone) Me nopa us ebefor
ea g
e40s ug gest
s1°ov ar
ian
such as the hypoestrogenic symptoms
of hot flashes and vaginal dryness.
aft
erme nopa usebe come spe ri
pheral insuffic
ie ncy(pre
ma tur
eov arianfai
lure)
;
conver
sionofa ndrogens,a ndrogens ma yo cc urinwome nwhoha verec
eived
This was the explanation to a UWORLD
question about a 50yo woman who took OCPs
hirs
utism. che mo the r
apyand/orra
dia t
iontherapy.
for 17 years and stopped 3 months ago, but is FSHi sspe cificformeno pause(lossof
not menstruating, is sexually active, and has
vaginal dryness but no pain or other issues. negati
vefeedb a ckonFSHd uet o e str
ogen)
.
She had simply hit menopause.
Andr
ogens Te
stos
ter
one
,di
hydr
ote
stos
ter
one(
DHT)
,andr
ost
ene
dione
.
S
OUR
CE DHTandt
est
ost
ero
ne(
tes
ti
s,AnDr
) ost
ene
dio
ne Pot
encyDHT>t
: e
stos
teone>
r
ADr
( enal
) andr
ost
ene
dio
ne.
F
UNC
TION Te
stosterone: Test
ostero
nei sconverte
dt oDHTby
Di f f
erent
iat
iono fepididymi s,v
asdefer
ens, 5α-reducta
se ,whichisinhi
bit
edb yfina
steri
de.
se mi nalve
sicl
e s(
inte
r nalg eni
tal
ia,exc
ept Inthema le,androgensareconver
tedtoe s
trogen
pr ostat
e). byc yt
ochromeP- 45
0a r
oma t
ase(pri
ma ri
lyin
Gr owthspur t
:penis,semi nalvesi
cle
s, adiposeti
ssuea ndtest
is
).
spe rm, musc l
e,RBCs . Aroma t
aseisthek eyenzymeinc onversi
onof
De epeningofv oi
ce. androgenstoe str
ogen.
Cl osingofe pi
phy s
ealpl at
e s(v
iaestr
ogen —a b us
eo fanabo l
ic
c onv er
tedfr
om t est
osterone). s
teroi
dst o fat
-freema s
s,mus clestr
eng t
h,
Li bido. andpe r
fo r
ma nc e.Suspe ctinme nwhopr esent
DHT: withcha ngesinbe ha vior(eg,aggres
sion)
,
Ea rl
y—d if
fere
nt i
ati
ono fpe nis,s
crot
um, acne,gyne c
oma sti
a,sma lltest
es(exogenous
pr ostat
e. t
e s
tos
terone hypotha lamic-pi
tuitar
y-
La te—pr ost
ateg r
owth, balding,sebac
eous gonadala xi
sinhib i
tion i ntr
atest
icula
r
g landa ct
ivi
ty. t
e s
tos
terone t esticularsi
z e,s permc ount,
azoospermia).Wome nma ypresentwith
vir
il
izat
io n(eg,hi r
sutism,a cne,breas
tatrophy,
ma l
epa tte
rnba ldne ss
).
UCT
IVE
—P Hy
SI Ogy S
Ol ecti oNi i
i 6
23
T
anners
tagesofs
exual
devel
opment
Tannerst
ageisas
si
gnedindepende nt
lytogeni
tal
ia
,pubichai
r,andbr
east(e
g,apers
oncan
haveTannerst
age2genit
ali
a,Ta nnersta
ge3pubichair
).Ear
li
e s
tde
tect
ables
econdar
yse
xua
l
chara
cter
is
ti
cisbre
astbuddevelopme ntingi
rl
s,te
sti
cula
renl
argementinboys
.
S
tag
eI S
tag
eII S
tag
eII
I S
tag
eIV S
tag
eV
Nosexu
alhai
r P
ubi
ch a
irapp
ears Coar
seni
ngofpub
ic Coar
sehai
racr
osspubi
s, Coar
sehai
rac
ros
spubi
san
d
Fl
at-
app
eari
ngch
est
wit
h (
pub
arche) ha
ir sp
ari
ngthi
gh medi
alt
hig
h
ra
is
ednipp
le T
est
icu
laren
lar
gemen
t Pe
niss
ize
/le
ngt
h Peni
swidt
h/g
lans Pen
isan
dtest
i
senl
ar
geto
B
rea
stbudfor
ms Br
east
enla
rges
,mound Br
easten
lar
ges,
rai
se
d ad
ults
iz
e
(
t
hel
arche) f
orms ar
eola
,moundonmo und Adul
tbr
eas
tcont
our
,ar
eol
a
fla
tt
ens
P
re-
pub
ert
al ~8
–11
.5y
ear
s ~1
1.
5–1
3ye
ars ~1
3–1
5ye
ars Us
ual
l
y>1
5ye
ars
Pr
ecoc
iouspuber
ty Appearanceo f2°s ex
ua lcharacter
isti
cs(eg,adrenar
che,thelar
che,me narc
he)be f
oreage8ye a
rsin
g
irlsand9y earsinboy s.s exho rmonee xposureorproducti
on l i
neargrowth,somati
cand
s
k el
etalma t
urati
on( eg,pre
ma turec l
osureofe pi
physe
a lpl
ates shortst
atur
e )
.Typesincl
ude:
Centr a
lp rec
oc i
ouspube rty(GnRHs ecret
ion)
:idi
opa t
hic(mostcommon; ear
lyacti
vat
ionof
hypotha la
mic -
pit
ui t
arygona dalaxis
),CNSt umors.
Peri
p heralprecociouspub er
ty(GnRH- independent
;s exhormonepr oducti
ono rexpos
ure
t
oe xoge noussexsteroids
):congenitaladrenalhyper
plasi
a,est
rogen-secr
eti
ngov ar
iantumo r
(
eg,
g ranulosacelltumor),Le y
d i
gc ellt
umo r,Mc Cune-Albri
ghtsyndrome.
UWORLD= A 14yo girl is brought to the office for evaluation of a bump on her chest just below the right breast.
The bump has been there for as long as she can remember, but it became a little larger 2-3 years ago. The bump
also becomes tender just before she starts her menses. Both breasts and axillae appear normal and exam shows
Tanner stage 5 breasts. There is a soft, raised, hyperpigmented, 0.5cm nontender lesion inferior to the right
breast. What is the cause of her presentation? Failed involution of the mammary ridge. The most common breast
anomalies in women and men are accessory nipples (polythelia, supernumerary nipple). They are due to failure
of involution of the mammary ridge. Accessory nipples are asymptomatic, but they may swell or become tender
similar to normal breast tissue before or during menses, pregnancy, and lactation. Findings include epidermal
thickening, hyperpigmentation, pilosebaceous structure of Montgomery areolar tubercles, smooth muscle
bundles (Areola), and possible mammary glands and multiple ducts.
6
ve R E
P ROD UCT
IVE—P ATHOl
Ogy
R
EPROD
UCT
IVE
—PA
THOl
Ogy
Sexchromos
ome Ane
upl
oidymos
tcommo
nlyd
uet
ome
iot
icno
ndi
sj
unc
tion.
dis
orders
Kl
inef
elt
ers
yndr
ome Male,4 7,
XXY. Dysge
nesisofs
eminifer
oustubul
es
A Tes
ticularatrophy,eunuchoi
dbo dyshape,
inhibi
n B FSH.
ta
ll,l
onge xtr
emi t
ies
,gynecomasti
a,f
e ma l
e Abnor
ma lLeydi
gc e
llfunct
ion te
stos
ter
one
hairdistr
ibuti
onA. Ma ypr
e s
entwith LH est
rogen.
developme ntaldel
a y
.Pres
enceofinactiva
ted
Xc hromo some( Barrbody)
.Commo nc auseof
hypog onadisms ee
ni ninf
erti
li
tywork-up.
A 15 yo patient is referred to the physician by a teacher who is concerned about the patient's learning and behavior. The patient's reading and writing
skills are significantly impaired compared to other classmates, and the patient often misbehaves in class despite receiving numerous detentions.
Cytogenetic studies show a karyotype containing 47 chromosomes. Which of the following findings are most likely to be present on further evaluation?
Tall stature, gynecomastia, and azoospermia.
T
urners
yndr
ome Fema l
e ,45,XO. Me nopa usebe f
oreme nar
c he.
B Shortstature(i
funtreat
ed;pr e
ventabl
ewi t
h e s
trogenl e
a dsto LH,FSH.
growthhor monetherapy)
, ovar
iandysgenesi
s Sexc hromo some( X,o rrarelyY)l o
sso ft
endueto
(st
reakov ary)
,shie
ldche s
tB,b i
cuspi
da ort
ic nond isj
unc ti
ondur ingme i
osisormi t
o si
s.
valve
,c oarctat
ion(f
emo ral<b rac
hialpuls
e), Me i
os i
se rr
orsusua ll
yoc curinpa ter
na lgametes
lympha ticdefect
s(res
ultinwe bbednec k s
pe rm mi ss
ingt hesexc hromo some .
orc y
stichy gr
oma ;l
ymphe demai nfeet, Mi t
osiserrorsoccura ft
erz ygot
ef ormation l
oss
hands),ho rs
eshoekidney,high-ar
chedpa l
ate, ofsexc hromos omei ns omeb utnota llcell
s
short
e ned4t hme t
acarpals. mos aickaryotype(eg. 45,
X/46XX) .
Mos tcommonc aus
eof1 °ame norrhe
a .NoBa r
r (
45 ,
X/46, XY)mo sai
c i
sma ssoci
a t
edwi th
bod y
. increasedriskforg onadob l
ast
o ma .
A nonstenotic bicuspid aortic valve manifests with an aortic ejection Pregnanc yispo s
sibleinso mec ases(IVF ,
sound, which is an early systolic, high-frequency click heard over the
right second interspace. As the valve calcifies, it may result in
exog enouse st
radiol-
17βa ndp rogest
erone).
progressive valvular dysfunction, manifesting with aortic stenosis.
Doubl
eYmal
es 47,XYY. Turner Syndrome -- Gonadoblastoma = Benign by definition, but more than
50% have coexisting dysgerminoma, which is malignant. Gonadoblastoma is
Phenotyp
ical
lynormal(usual
lyundia
gnosed)
, a
complex neoplasm composed of a mixture of gonadal elements, such as
veryt
all
.No r
ma lf
ert
ili
ty.Maybea s
soci
ated primordial germ cells, immature Sertoli or granulosa cells of the sex cord,
withsev
ereacne,l
earningdis
abil
it
y,aut
is
m and
gonadal stromal cells. It is most often associated with the presence of a Y
spect
rum di
sorder
s. chromosome in abnormal chromosomal karyotypes. Turner patients with
Ovotes
tic
ulardi
sor
der 4
6,XX>46 ,
XY.
ofs
exdev el
opment Bothov ar
ianandt
estic
ula
rtis
suepr
ese
nt
(
ovote
sti
s)
;ambig
uo usge
nit
alia
.Pr
evi
ous
ly
ca
lle
dt r
uehermaphrodi
ti
sm.
UWORLD= A 17yo boy is brought to the office for evaluation of bilateral breast enlargement. He first noticed it a few months ago and says that it is slightly painful. His parents are concerned that
his breasts are gradually becoming more prominent. The patient is in special education classes due to a long-standing history of learning disabilities. Height is at 95th percentile and weight is at
the 25th percentile for age and sex. Symmetrical glandular tissue is palpated under both nipple-areolar complexes. His sense of smell is normal, and his testicles are small and firm. Labs would
most likely show what findings? Increased FSH. Klinefelter syndrome. Lack of feedback inhibition results in excess gonadotropins.
A 12yo girl is brought to the clinic by her parents, who are concerned about her loss of interest in playing sports at school. During a recent competition, she walked off the field in the middle of the
game, complaining about pain in her legs. The patient has no other medical conditions and takes no medications. Her vaccinations are up to date. Physical exam shows pulsatile vessels in the
intercostal spaces and diminished femoral pulses relative to brachial pulses. Her symptoms are most likely associated with what condition? Turner Syndrome. She most likely has coarctation of
the aorta, which typically affects the region just distal to the left subclavian artery.
A newborn girl is evaluated in the nursery after an uncomplicated spontaneous vaginal delivery to a 29yo primigravida. The mother declined prenatal testing and ultrasound exam during the
pregnancy. Her pregnancy was otherwise uneventful and she took prenatal vitamins. Exam of the neonate shows a posterior neck mass and bilateral nonpitting edema of the hands and feet.
Femoral pulses are diminished. Neck ultrasound reveals a mass composed of cystic spaces separated by connective tissue. What is the most likely underlying mechanism for this patient's
condition? Loss of paternal chromosome X. The posterior neck mass is a cystic hygroma, and bilateral extremity swelling is consistent with lymphedema. The diminished pulses suggest
coarctation of the aorta, so this patient must have Turner syndrome, which is due to loss of the paternal chromosome X.
A 6yo girl is brought in for evaluation of short stature. Her parents have noticed that she bears little resemblance to her 2 older siblings. The patient's mother and father are 5'8" and 6' tall,
respectively. On physical exam, the patient's height is 3 standard deviations below the mean for her age. Other findings include low-set ears, a high arched palate, a webbed neck, and cubitus
valgus. Chromosomal analysis reveals 45,XO karyotype. The patient is started on medication to improve growth and normalize her height. What intracellular pathway is stimulated by the
medication used in this patient? JAK-STAT pathway. This patient has Turner syndrome, which is typically treated with growth hormone, which acts on cell surface receptors to stimulate
production of IGF1 in the liver. The cell surface receptor is a JAK nonreceptor tyrosine kinase, which phosphorylates several tyrosine residues in the intracellular domain of the GH receptor.
RepRoduct ive R E
PRODUC
TIVE
—P A
T Ogy S
HOl ecti oNi i
i 6
25
Diagnosi
ngdisor
der
s T
est
ost
erone L
H Di
agnos
is
ofsexhormones
Normally, testosterone has a negative feedback
on LH, but if the testosterone receptor is defective,
it will not suppress LH. In exogenous or excess
testosterone their will be an inhibition of LH.
In 1' hypogonadism, there will be LH but the

gonads will not respond and make testosterone
regardless of LH, possibly due to leydig cell
malfunction. In 2' hypogonadism, the issue
is in the hypothalamus or pituitary.
Otherdi
sor
der
sofs
ex Di
sagr
eementbet
we e
nt hephenotypi
cs e
x(exte
rnalg
enit
ali
a,i
nfuenc
edbyhormonall
evel
s)
devel
opment a
ndthegonada
lsex(tes
tesvsova
r i
es,c
orres
pondswit
hYc hro
mosome).
Inc
ludest
heter
ms
p
seudohe
rmaphrodi
te,hermaphrodit
e,andint
ers
ex.
46,
XXDSD Ov a
riespr
esent,butext
erna
lgeni
tal
iaarevi
ril
iz
edo ramb i
guous.Duetoexce
ssi
veand
inapprop
riat
ee x
po s
uretoandr
ogeni
cster
oidsduri
nge arl
ygest
ati
on(eg,
congeni
ta
ladre
nal
hyperpla
siaorexogenousadmi
nis
trat
ionofandrog
e nsduri
ngpregna
ncy).
46,
XYDS
D Te
ste
spres
ent,
butext
ernalg
enit
ali
aar
efemaleora
mbi
guo
us.
Mos
tco
mmo
nfo
rmi
sandr
oge
n
i
nsens
it
ivi
tys
yndr
ome( t
est
icul
arf
emini
zat
ion)
.
Di
sor
der
sbyphysi
cal UTERUS b
REA
STS D
ISO
RDE
RS
c
har
act
eri
sti
cs ⊕ ⊝ Hyper
g onado
trop
ichy pogona
dis
m(eg,Tur
nersynd
rome,g
enet
icmo s
aic
ism,
pur
eg onadaldy
sgene s
is
)
Hypogonadotr
opi
chy pogonadi
sm(e
g,CNSl es
ions
,Kal
lmannsyndr
ome)
⊝ ⊕ Ut
erov
ag i
nala
gene
sisi
nge
not
ypi
cfe
mal
eora
ndr
oge
nins
ens
it
ivi
tyi
n
g
enotypi
cma l
e
⊝ ⊝ Ma
leg
enot
ypewi
thi
nsuf
fic
ientpr
oduc
tio
noft
est
ost
ero
ne
Pl
ac ental
aroma
tas
e I
nabil
it
ytosynthes
izeest
rogensf
roma ndr og
e ns
.Ma s
culi
nizat
ionoff
emal
e(46,
XXDSD)inf
ant
s
defici
ency (
amb i
guousgenit
ali
a)
,s er
um tes
tos
teronea nda ndros
tenedi
one.Canpr
ese
ntwit
hmat
erna
l
The mother may experience facial hair growth and
voice deepening during the pregnancy due to high
vi
ri
li
zati
ond uri
ngpregnancy(f
eta
landr ogenscrossthepla
c e
nta)
.
serum levels of testosterone and androstenedione.
Andr ogeni ns ens it ivi t y De f

ectinandrogenre
cept
orresult
inginnorma l-
appear
ingf
ema l
e(46,
XYDSD) ;fe
ma leext
erna
l
syndr ome g
enita
liawit
hs c
antaxi
ll
aryandp ubi
chair,rudimentar
yvagi
na;ut
erusandf
all
opiantubes
Both LH and testosterone are high due to a
lack a
bsent.Pa
tie
ntsdeve
lopnorma lf
uncti
oningt e
stes(
oft
enfo
undi nla
biamajo
ra;s
urgical
ly
of negative feedback. The lack of pubic hair is
very significant and differentiates this from
r
emo v
ed t
o pre
ventmali
gnancy). t
esto
sterone,est
rog
en,LH (
vssexchr
omosome dis
order
s)
.
other
conditions like Mullerian agenesis, where the
5α-reduc
tas
e Aut
osomalr
eces
si
ve;sexl imi te dt og ene ti
cma l
e s( 46,XYDSD) .Ina b ili
tytoc onv e rtt e sto steronet o
defici
enc
y DHT.Amb i
guousgeni tali
aunt ilp ube rty,whe n t estoste r onec aus e sma sc ulini z ation/g r o wt ho f
ex
ter
nalge
nit
ali
a.Testos terone /estrog enl evelsa reno r ma l; LHi sno rma lor.I nt er na lg eni ta l
ia
ar
enormal
.UWORLD= A 22yo primigravida who recently immigrated from DR has a normal vaginal delivery. The infant is phenotypically
male but has hypospadias, a small phallus, and his testes are well-developed but in the inguinal area. Serum testosterone is
normal as well as his BP. What enzyme is most likely deficient? 5a-reductase. No DHT; male pseudohermaphroditism.
Kal
lmanns
yndr
ome Fa
iluret
oc omple
tepuber
ty;aformo fhypog
onadot
rop
ichypogonadi
sm.Defe
cti
vemigr
ati
onof
GnRH- r
eleas
ingneur
onsands ubse
quentfai
lur
eofol
fac
torybulbst
odeve
lop s y
nthesi
sof
GnRHi nthehy po
thal
amus ;
hy pos
mi a
/anos
mia; GnRH, FSH,LH, t
est
ost
ero
ne.I
nfer
ti
li
ty(
low
s
pe r
mc ountinmales
;ame nor
rheainfemales
).
UWORLD= A 14yo boy is brought in by his mother. She is concerned because although tall, her son looks much younger than his peers and shows
no signs of "masculinity." On physical exam, the boy has poorly developed secondary sexual characteristics. He is unable to distinguish smells but
has good visual acuity. What hypothalamic-pituitary-gonadal pathway is most likely defective in this patient? The hypothalamic-pituitary part which
releases GnRH to affect pituitary secretions. He has Kallman syndrome, which is due to failure of GnRH-secreting neurons to migrate from their origin
in the olfactory placode to their normal hypothalamic location. Most often its due to a mutation in the KAL-1 or Fibroblast growth factor receptor-1 gene.
6
ve R E
P ROD UCT
IVE—P ATHOl
Ogy
UWORLD= A 24yo woman, g1p0, comes to labor and delivery triage at 28 weeks gestation due to intense abdominal pain, vaginal bleeding, and few fetal movements. Her T=98F, BP=170/96,
and exam shows a tense abdomen with tender uterus. Ultra- sound shows a hematoma between the placenta and uterine wall and no fetal cardiac activity. Lab results have Hb=9.2 (L),
platelets=60,000 (L), and normal AST & ALT. The patient is hospitalized and is bleeding from her vagina, gums, and IV sites. Blood is in her foley catheter as well. What is causing her
bleeding?
Release of tissue factor into maternal circulation. DIC is a life-threatening obstetric complication, and it is mediated in pregnancy by tissue factor (thromboplastin), which is found in high
concentrations in the placental trophoblast. This patient's presentation is consistent with abruptio placentae, which can result from severe hypertension, as in this patient. The abruption lead
Pr egnanc yc ompl ic ations to fetal demise and caused DIC, which is common.
Abr
upt
iopl
acent
ae Pr
ema t
ur esepa ra
tion( p
a rti
alorc omplete)of
placentaf r
om ut erinewa llbeforede l
iv
ery
ofinfant.Riskf actors:trauma( e
g ,mo t
or
v
e hicleac ci
de nt
),smo king ,hypertens
ion,
preeclamps i
a, coca i
nea buse .
Pr
e s
e ntati
on:a brupt ,pa infulbleeding
(
co ncea l
edo ra ppare nt)inthirdt ri
me s
ter;
possibl
eDI C( me dia t
edbyt is
suef act
or
a
c tiva
tion),ma terna lshoc k,fet
aldi s
tr
ess.Lif
e
t
hr eat
e ningfo rmo the ra ndf e
tus.
Comp
let
eab
rupt
io
nwith P
a r
ti
al
abru
pti
on(
bl
uearr
ow)
c
onc
eal
edhemor
rha
ge wi
thappa
rent
hemor
rha
ge(r
ed
arr
ow)
Morbidl
yadher
ent Defectivede cid ua llayr a
e b
no r
ma l at
tac
hme nt
pl
acenta ands epa r
ationa fterdeliv
e r
y.Ri skfactor
s:
prio
rC- sectiono ruterinesurg eryinvolvi
ng P
lac
ent
a
my ome t
ri
um, infa mma t
ion, placentaprevia
, Normal acc
ret
a
p
lac
enta
advanc edma te rnala ge,multip ari
ty
. Threetypes P
lac
enta
St
rat
um i
ncre
ta
dist
ing uis
ha b l
eb ythed e
ptho fpene t
rat
ion: basa
li
s
—pl acentaa ttache sto
my ome t
rium wi t
ho utpe netratingit;mo st P
lac
enta
p
ercr
et
a
commo nt ype .
—p lacentape ne tr
atesinto
my ome t
rium.
—p l
acentape netrat
es
(“perforate s
” )thr oughmy ome tri
um a ndinto
uteri
nes erosa( inv adesent i
reut erinewa ll
);
canr esultinpl a centalattachme nttorectum
orbla dder( ca nr esultinhe ma t
ur i
a).
Prese
nt ation: ofte nde t
e ct
e donul tr
a s
oundpr io
r
tode li
v er
y.Nos eparati
onofpl acentaa f
ter
deli
v ery pos tpartum bl eeding( canc ause
Shee ha nsy ndr ome )
.
Pl
acent
apr a
evi Att
achme ntofp la
centatoloweruteri
ne
segme ntov e
r( or<2c mfrom)inte
rnal
cer
v i
ca los.Riskfactors
:multipa
rit
y,pr
ior
C-section.Assoc i
atedwithpainl
essthi
rd-
tr
ime sterbleeding.A“ pre
view”ofthe
placent aisvi
siblethroughcervi
x.
P
art
i
alpl
ace
nta Co
mpl
et
epla
cen
ta
pre
via pr
evi
a
RepRoduct ive R E
PRODUC
TIVE
—P A
T Ogy S
HOl ecti oNi i
i 6
27
Pr
egnanc
ycompl
icat
ions(
cont
inue
d)
Vas
apr
evi
a Fet
alvesselsrunov er, ori nclosep r
oximity
t
o,c er
vicalos.Ma yre sultinv ess
elrupture, Umbi
l
ica
l
exsa
ngui nati
on, fet
a lde ath.Presentswith co
rd
tr
iadofme mbr aner upt ure,painles
sva g
ina l
blee
ding ,fet
albr a
dy c ardia(<1 10beats/
mi n).
P
lac
enta
Eme rgencyC- sectionus uall
yindicated. P
lac
ent
a (
suc
cent
uri
at
e P
lac
ent
a
Frequentlyassociat
e dwi thvelamentous l
ob
V
e
e
)
l
ament
ous
umb il
icalcordinse rtion( cordinser
tsin at
ta
chment
chori
oamni oti
cme mb r
a neratherthan V
asap
rev
ia
pla
centa f
etalves s
e lstrav
e ltoplace
nt a
unprotectedbyWha rto njell
y).
Post
par
tum Dueto4T’ :To
s ne(ut
e r
ineatony ;most
hemor
rhage commo n
),Trauma(lacer
ati
o ns,inc
isions,
ute
riner
upture,Thr
) ombin( coagulopathy)
,
Tis
sue(r
etai
nedproductsofc oncepti
o n)
.
Ec
topi
cpr
egna
ncy I
mp lantat
iono ffer
ti
li
ze dovum inas i
teot
her Pa
in+/
−b leeding.
A
t
ha ntheut erus,mostofteninampullaof Ri
skf
actor
s:
f
all
o piantubeA.Sus pectwithhis
toryof Pri
orectopicpregnancy
ame norrhea,lo
we r
-t
ha n-expect
edris
einhCG His
toryo finfe
rti
li
ty
basedonda tes,andsud denlowerabdomina
l Sal
pingit
is( PI
D)
pai
n;c onfir
m wi t
hul t
rasound.Often Ruptureda ppendi
x
cl
inicall
ymi stak
enfora ppendici
ti
s. Pri
ortuba lsur
gery
Smok i
ng
Advancedma t
ernalag
e
Amni
oti
cflui
dabnor
mal
it
ies
Pol
yhy
dra
mni
os Toomucha mnioti
cfuid.Ofteni dio
pathi
c, butas
soci
ate
dwit
hfet
almal
for
mat
ions(e
g,
es
ophag
e al
/duodenalat
res
ia,
a ne nce
phaly;bothres
ulti
nina
bil
it
ytos
wall
owa
mni ot
icfui
d),
mate
rnaldi
abe t
es,f
eta
lanemia ,mul t
ipl
eg est
ati
ons
.
Ol
igohydr
amni
os Tooli
ttl
eamnioti
cfuid.Ass
oci
at
edwithpla
centali
nsuf
fic
ienc
y,b
ilat
era
lrena
lag
ene s
is
,post
eri
or
uret
hralva
lve
s(inmales
)andres
ult
anti
nabil
it
ytoexcr
eteuri
ne.Anyprof
oundol
igohydr
amnios
cancausePot
terse
quence.
UWORLD= A 32yo woman at 28 weeks gestation has an ultrasound that shows markedly elevated amniotic fluid levels. She has been feeling short of breath when she is supine but has no other
symptoms. She has a history of epilepsy that is well-controlled with medication. She does not use tobacco, alcohol, or drugs and her immunizations are up to date, and she has no allergies.
Physical exam shows an abdominal circumference that is larger than expected for gestational age. What fetal anomaly most likely accounted for this patients polyhydramnios? Anencephaly.
Polyhydramnios can be due to decreased fetal swallowing or increased total urination. Fetal anomalies with impaired swallowing include the things above, such as gastrointestinal obstruction
and anencephaly from cranial neural tube defects. Causes of increased fetal urination include high cardiac output due to anemia or twin-to-twin transfusion syndrome. Maternal diabetes and
multiple gestations tend to cause milder polyhydramnios than the aforementioned fetal anomalies. This patient's prenatal use of anti-epileptic therapy is a substantial risk factor for fetal neural
tube defects such as anencephaly.
A 35yo woman, G2P1, comes to the office for a routine prenatal visit. Her first child was born with a hydrocele and syndactyly of the first and second toes. The patient has no significant medical
problems and takes no medications except for a multivitamin. Examination reveals clear lungs and normal first and second heart sounds. The abdomen is soft and nontender. Uterine size, fetal
movements, and fetal cardiac activity are all within normal limits. The patient undergoes amniocentesis during the 18th week of pregnancy. Amniotic fluid analysis shows an increased level of
acetylcholinesterase. The patient's amniocentesis results most likely suggest failure of which process? Fusion of the edges of the neural plate. Failure of the rostral neuropore to close results in
anencephaly, whereas impaired closure of the caudal neuropore results in spina bifida. If either fail to fuse, an opening persists and allows leakage of AFP and AChE into the amniotic fluid.
A 6 hour old boy is in the newborn nursery with feeding difficulties. The patient was born at 39 weeks gestation to a 33yo primigravida via cesarean delivery due to failure to progress and late
decelerations seen on fetal heart tracing. Apgar scores were 8 and 9, but exam shows an infant with excessive drooling and occasional coughing. Cardiac, respiratory, and abdominal exams are
otherwise normal at rest. When the infant attempts to breastfeed, however, several bouts of coughing and perioral cyanosis develop with oxygen saturation of 85% on room air. What is the most
likely cause of his condition? Failure of primitive foregut to separate from airway. The infant's presentation is concerning for tracheoesophageal fistula with esophageal atresia. Prenatal ultrasound
may demonstrate polyhydramnios due to the inability of the fetus to swallow amniotic fluid.
A 1 hour old boy is in the neonatal ICU with tachypnea and hypoxia. The infant was born at 39 weeks gestation via cesarean delivery due to variable decelerations. The pregnancy was
complicated by a lack of prenatal care. The infant weights 7lb 1oz. Physical exam shows a flattened nose and bilateral club feet. Breath sounds are markedly dminished bilaterally. The infant is
intubated and mechanically ventilated, but his oxygen levels do not improve. The infant dies 1 hour later. What is most likely to be found during autopsy? Renal agenesis. The infant has features
consistent with Potter sequence; pulmonary hypoplasia along with facial and lower limb deformities. The renal anomaly leads to decreased urine output by the fetus. Classically see bilateral
renal agenesis. Since the volume of amniotic fluid depends on fetal urine production, affected infants have severely reduced (oligohydramnios) or absent amniotic fluid (anhydramnios). The
lack of amniotic fluid causes external compression of the face and lower extremities. Compression of the umbilical cord leads to fetal heart rate anomalies.
6
ve R E
P ROD UCT
IVE—P ATHOl
Ogy
Hydat
idi
for
m mol
e Cyst
icswell
ingofcho r
ionicvil
liandprol
ifer
ati
onofchori
onice
pithel
ium (o
nlytrophobla
st)
.
A
Pre
sentswit
hv ag
inalbleeding,uter
ineenlarg
ementmo r
ethanexpected,pel
vi
cp re
ssur
e /
pain.
Assoc
iate
dwi t
hhCG- me dia
tedsequela
e: e
arl
ypreec
lampsi
a(bef
o r
e2 0weeks)
,theca-
lut
eincyst
s,
hyper
e mesi
sgravi
darum, hyperthyr
oidi
sm.
Tre
atme nt
:dil
ati
ona ndc uret
tageandme thotr
exa
te.Monit
orhCG.
Compl
etemol
e p57 (-) Par
ti
almol
e p57 (+)
K
ARy
OTy
PE 46,
XX;46,
XY 6
9,XXX;69
,XXY;
69,
XYY
C
OmP
ONE
NTS Mostcommonlyenucl
eat
edegg 2s
per
m +1e
gg
B +si
ng l
esper
m(subs
equent
ly
dupl
icat
espa
ter
nalDNA)
H
IST
OlO
gy Hydropi
cvill
i,ci
rcumfer
enti
al Onlys
omev il
lia
rehydro
pic,
anddiff
usetrophobl
ast
ic f
ocal
/minimalt
rophobl
ast
ic
pro
lif
era
tion pr
oli
fer
ati
on
F
ETA
lPA
RTS No Y
e pa
s( r
ti
al=f
etlpa
a rts
)
S
TAI
NI
NgF
ORP
57P
ROT
EI
N ⊝(
pat
erna
llyi
mpr
int
ed) ⊕(
mat
erna
llye
xpr
ess
ed)
U
TER
INES
IZ
E —
A complete mole most commonly results
from the fertilization of an ovum that has h
Cg (Can cause theca-lutein cysts)
no maternal chromosomes (either due to
absence or inactivation). The chromosomes I mAg
INg “
Ho ne
ycombed”ut
erusor Fe
talpa
rts
from the haploid 23X sperm are then
duplicated, forming diploid 46,XX tissue “
clus
ter
sofg
rapes
”A,
that contains only paternal DNA.
“
snowst
orm”
Bonultr
aso
und
R
ISKO
FINV
ASI
VEmO
lE 1
5–20
% <5
%
R
ISKO
FCHO
RIO
CAR
CIN
OmA 2
% Ra
re
Chor
ioc
arc
inoma Rare;cand evelopdur ingoraft
erpreg nanc
y B
A
inmot hero rba by.Ma l
ignancyof
tr
op hobla
s t
ictissueA (c y
totr
ophoblast
s,
syncyti
otropho blas
ts;noc
) hori
onic
vil
liprese
nt .f requenc yofbil
ate
ral/
mul ti
pletheca-lute
inc yst
s.Pres
entswith
abno r
ma l hCG,s hortnes
sofbreath,
hemo ptys
is.He matogenoussprea
dt olungs
“
c a
nno nball”me t
ast
a s
esB.
Treat
me nt:me tho t
rexate
.
UWORLD= A 16yo girl comes to the ED with vaginal bleeding. Her last menstrual period was 12 weeks ago. She is sexually active and does not use contraception. The patient had a miscarriage
last year that required a dilation and curettage. Urine pregnancy test is positive. Transvaginal ultrasound demonstrates an intrauterine gestational sac without fetal cardiac activity, and a D&C is
performed. Pathology shows fetal tissue, focal trophoblastic hyperplasia, and some enlarged villi interspersed with normal villi. What is the most likely diagnosis?
Partial mole. Hydatidiform moles are premalignant gestational trophoblastic disease characterized by abnormal placental trophoblastic proliferation, leading to very high bhCG. The partial moles
usually have a triploid karyotype containing maternal and paternal DNA, with an extra chromosome set of paternal origin.
A 41yo woman comes to the office for evaluation after a positive home urine pregnancy test. Her last menstrual period was 12 weeks ago. For the past month, the patient has had increasing
nausea. She vomits several times a day and has difficulty keeping any food down. The patient has 3 children, all born at term via cesarean section. On this visit, ultrasound demonstrates
echogenic intrauterine tissue without an amniotic sac and multiple bilateral ovarian cysts. D&C is performed, and hydropic villi are evacuated from the uterus. What should be closely monitored
after the procedure? b-hCG. She has a complete mole, composed of multiple cystic edematous hydropic villi that have a macroscopic appearance of a "bunch of grapes" as a result of
trophoblastic proliferation. Ultrasound would confirm the lack of a fetal pole and amniotic sac. Complete moles are p57 negative due to absence of maternal genome. Monitoring bhCG is
important due to the high risk of malignant transformation; a level that rises and plateaus is a red flag for neoplastic conversion (invasive mole, choriocarcinoma).
A 28yo woman, g2p2, comes to the office with worsening shortness of breath over the past week. She had a recent episode of hemoptysis. The patient has also had ongoing vaginal bleeding
after an uncomplicated vaginal delivery of her son 9 weeks ago. She has no bleeding elsewhere, and has not resumed sexual intercourse. On physical exam, her uterus is enlarged and the
adnexa are normal. Lab studies show markedly increased bhCG. Chest radiograph shows multiple bilateral lung nodules. What would most likely be found on endometrial curettage in this patient?
Proliferation of cytotrophoblasts & syncytiotrophoblasts. Choriocarcinoma is a malignant tumor of the trophoblast and is most commonly preceded by a normal pregnancy but can occur following
any pregnancy (molar, ectopic, aborted). The lungs are the most common site of distal metastasis, hence the hemoptysis and shortness of breath.
A 29yo man comes to the office due to increased sweating, heat intolerance, insomnia, and unintentional weight loss over the past 4 weeks. The patient has also noticed that his right testis feels
bigger than the left but has had no scrotal pain. He has no prior medical problems and takes no medications, nor does he use tobacco, alcohol, or drugs. BP=120/70, P=108, and on exam his
thyroid is mildly enlarged. Testicular exam reveals an enlarged, nontender right testicle. Lab testing shows elevated serum thyroxine and T2 levels. Scrotal ultrasonography demonstrates a
hypoechoic mass within the right testicle. Elevated levels of what would most likely explain his symptoms? hCG. The beta subunits of hCG and TSH share significant homology, allowing it to
bind TSH receptors. hCG is normally produced by the placenta but can also be released by a number of malignancies, especially choriocarcinoma and nonseminomatous germ cell tumors. This
patient most likely has a testicular germ cell tumor producing large quantities of hCG, causing paraneoplastic hyperthyroidism and his presenting symptoms of weight loss and heat intolerance.
RepRoduct ive R E
PRODUC
TIVE
—P A
T Ogy S
HOl ecti oNi i
i 6
29
Hyper
tens
ioni
npr
egnanc
y
Gestat
iona
l BP>1 40/90mm Hgafte
r20t
hwe eko
f Tr
e a
tment:anti
hypert
ensi
ves(Hydr
ala
zine,
hypert
ensi
on ge
sta
tion.Nopre-
exi
st
inghype
rte
nsi
on.
No α-Me t
hy l
dopa,La
betal
ol,Nif
edip
ine)
,del
ive
r
pr
ote
inur i
aore
nd-or
gandamage. at37–39we e
ks.Hypert
ensi
veMo msLo v
e
Nifedi
pine.
Pr
eec
lamps
ia New- ons ethypert
e nsio nwi the i
the rpr ot
einuri
a Tr
e a
tme nt:ant
ihype
rtensi
ves,I
Vma gnesi
um
orend- or g
andy sfunc t
iona ft
e r20t hwe e
k s
ulfate(t
opr e
ventse
izure)
;definit
ivei
sdeli
ver
y
ofge stat
ion( <20we ekss ug gestsmol ar offe
tus.
pregna nc y
). Pr
oteinuri,Ri
a singBP( ne
w-onse tHTN),
Cause dbya bnorma lpl ace ntals pi
ra lar t
eri
es End-o r
gandy s
funct
ion(eg,pulmo nar
yedema).
endot heli
aldy sf
unc ti
o n,v asocons tric
tio
n,
is
che mi a.
I
nc i
de nc e inpa tient swi t
hpr e-existing
hype rtensio
n, di
a be t
e s,chr onick idne yd i
seas
e,
autoimmunedi sorde rs(eg ,ant i
pho s
pho li
pid
anti
bod ysyndrome ) .
Comp li
c ati
ons:place ntala brup ti
o n,
coag ulop a
thy,rena lfailure ,pulmo na ry
edema ,uteropla
c ent alinsuf fici
enc y;ma y
l
e adt oe cl
amps i
a( + seizure s
)a nd/ orHELLP
syndr ome .
Ec
lamps
ia Pre
ecl
ampsi
a+ma te
rnalse
izure
s. Tr
eat
ment:I
Vma gnesi
um s
ulfa
te,
Mater
nalde
athduetos
troke
,intr
acr
ani
al a
nti
hype
rtens
iv
es,i
mme di
atedel
ive
ry.
hemorr
hage,
orARDS.
HEL
LPs
yndr
ome Hemol
ysi
s,ElevatedLiverenzymes
, Tr
eat
ment
:imme
dia
ted
eli
ver
y.
LowPlat
ele
ts.Ama ni
fest
ati
onofseve
re
pr
eec
lampsia
.Bl oodsme ars
howsschi
stoc
ytes
.
Canl
eadtoDI Ca ndhepati
csubc
apsular
he
matomas rupture sever
ehypotens
ion.
Gynec
ologict
umor Incidenc e(US)—e ndome t
rial>o vari
an> CEOsoft
eng
ofom be
r stt
owor
sta
sthe
yge
t
epi
demiology cervi
c a
l;cer
vicalcancerismor ecommo n ol
der
.
worldwideduet olackofscreeningorHPV
va
c cinati
on.
Prognos i:Ce
s r
vical(bes
tp rognosis
,diagnos
ed
<4 5y ear
sold)>Endo me tri
al(middle-
aged, a
bout55
year
so l
d)>Ov arian(worst
pr
og nosis
,> 65 y
ears)
.
6
ve R E
P ROD UCT
IVE—P ATHOl
Ogy
Vul
varpat
hol
ogy
Bart
holi
ncy
sta
nd Duetoblocka
geofBa rt
hol
ingl
andduc
tca
usi
ngaccumulat
ionofgl
andfui
d.Maylea
dtoa
bsc
ess
absc
ess 2°toobst
ruct
ionandinfammati
onA.Usua
llyi
nrepr
oducti
ve-
agefe
male
s.As
soc
iat
edwi
thN
g
o nor
rhoaei
e nfec
tio
ns.
L
ichens
cler
osus Thinningofepi
dermiswit
hfibr
osi
s/s
cle
rosi
sofder
mis.Pr
esentswi
thpor
cel
ain-
whit
epl
aque
s
witharedorvi
oletbor
d e
r.Ski
nfragi
li
tywit
herosi
onsca
nbeo bs
erv
edB.Mo stc
ommo ni
n
postmenopa
usalwome n.Beni
gn,butsl
ight
lyi
ncrea
sedri
skforSCC.
L
ichensi
mple
x Hype
rpl
asi
aofvul
vars
quamousep
ithel
ium. Pr
ese
ntswi
thleat
hery
,thi
ckvul
vars
k i
nwit
h
chroni
cus e
nhancedsk
inmarki
ngsduet
ochroni
cr ubbi
ngorscr
atc
hing.Beni
gn,nor
iskofSCC.
Vul
varc
arc
inoma Car
cinomaf r
oms quamouse pi
theli
all
iningofvulv
aC. Rare.Pr
ese
ntswithl
eukopl
aki
a,bi
opsy
of
tenrequir
edtodis
tinguis
hc arc
inomaf r
om otherca
uses
.
HPV-re
lat
e dvul
varcar
c i
noma —a s
soci
ate
dwi thhigh-
ri
skHPVt ype
s1 6
,18.Ris
kfac
tor
s:multi
ple
par
tner
s,earl
ycoit
arche.Usuall
yinreproduct
ive-
agefe
ma l
es.
Non-HPVv ulva
rcarci
noma —us ual
lyf
roml ong-
sta
ndingli
chenscl
eros
us.Femal
es>70yearsold
.
Ext
ramammar
yPa
get I
ntr
aepi
thel
ialadeno
c a
rci
noma.Carc
ino
mai nsi
tu,
lowri
skofund
erly
ingcar
cinoma(v
sPage
t
di
seas
e di
sea
seoftheb r
eas
t,whichi
sal
waysas
soc
iat
edwithund
e r
lyi
ngcar
cinoma
).Pre
sent
swit
h
pr
uri
tus,
erythema,crus
ti
ng,ul
cer
sD.
A B C D
I
mper
for
atehymen Fa
il
ureofhyme ncentr
alepi
thel
ialcel
lst
odegenerat
ea tbir
th.Acc
umula
ti
onofvagi
nalmucusa
t
Presents with eugonadotropic amenorrhea. bi
rt
h se
lf-
reso
lvi
ngbulgeinintr
oit
us.I
funtr
e a
ted,leadsto1°a
menor
rhea
,cyc
licabdo
minal
Patient will have fully developed secondary
sexual characteristics (so normal levels of pai
n,hematocol
pos(ac
cumulati
onofme nst
rualbloodinv agi
na b
ulgi
ngandbl
uishhymena
l
estrogen and gonadotropins) but incomplete membrane)
.
canalization of the vaginal plate.
Vagi
nal
tumor
s
Vagi
nal s
quamousc
ell Us
ual
ly2
°toc
erv
ica
lSCC;
1°v
agi
nalc
arc
ino
mar
are
.
car
cinoma
Clearc
ell Af
fec
tswome
nwhoha
dex
pos
uret
oDESi
nut
ero
.
adenocar
cinoma
Sar
comabot
ryoi
des Embryo
nalrha
bdomyosar
comav aria
nt.
Af
fec
tsgir
ls<4year
sold;
spindle
-shapedc
ells
;de
smin⊕.
Pr
ese
ntswithc
lea
r,gr
ape-
lik
e ,
po l
ypoidmassemer
gingf
romv
agi
na.
UWORLD= A 16yo girl comes to the office due to pelvic and crampy lower abdominal pain that seems to recur at the beginning of each month and resolves after a day or two. She thinks the pain
began approximately 6 months ago, and it is worsening significantly each month. The patient has never had a menstrual period. She and her boyfriend have not had any kind of sexual intercourse,
including digital, oral, vaginal, or anal (this description was interesting, why so specific?). The patient's weight, height, and BMI are average for age and sex, and she has fully developed secondary
sexual characteristics. Exam reveals a palpable mass anterior to the rectum, and bhCG is negative. What is the most likely diagnosis? Imperforate hymen. Hematocolpos. This is an obstructive
lesion caused by incomplete degeneration of the central portion of the fibrous tissue band connecting the walls of the vagina. At birth, vaginal secretions stimulated by the mother's estrogen can
cause mucocolpos (accumulation of mucus in the vaginal canal), which may manifest as a bulging introitus. If the condition remains undiagnosed, the mucus is reabsorbed and the child will be
asymptomatic until menarche. The patient may then present with primary amenorrhea and normal secondary sexual characteristics with cyclic abdominal pelvic pain due to accumulation of
menstrual blood in the vagina and uterus. Hematocolpos manifests as a vaginal bulge or mass anterior to the rectum.
RepRoduct ive R E
PRODUC
TIVE
—P A
T Ogy S
HOl ecti oNi i
i 6
31
UWORLD= A 35yo nulliparous, mildly obese woman is diagnosed with CIN3. She has been sexually active for 15 years and has had 4 lifetime partners. She has been monogamous with her
current partner for several months and takes OCPs consistently. The patient does not use condoms and douches regularly to "stay fresh." Menarche occurred at age 9, and her menses recur
every 28 days and last 6 days. She had a plantar wart a few years ago, but otherwise has no medical problems. She drinks 1-2 glasses of wine every night but does not use tobacco or illicit drugs.
The patient's mother had breast cancer at age 42. What is the most significant factor that predisposed her to cervical abnormalities? Lack of barrier contraception. Squamous Cell Carcinoma is
preceded by CIN due to HPV 16 or 18 infection. Nulliparity, early menarche, and obesity increase the risk of endometrial cancer. Douching is a risk for bacterial vaginosis because it disturbs the
vaginal ecosystem. Alcohol consumption (liver/breast) and nulliparity/early menarche/obesity (endometrial cancer) are not one of her many risk factors.
Cer
vic
alpa
thol
ogy
Dyspl
asi
aand Dis
orderedepit
he l
ialgro
wt h;beginsa tbasall
a ye ro fs qua mo columna rj unc tion( trans fo rma tion
c
arci
nomainsi
tu zo
ne)a ndexte
ndsout wa r
d.ClassifiedasCI N1 ,CI N 2,o rCI N3( sev e re ,ir re ve rsibledy s
p l a siaor
Below are more A
ca
rcinomains i
tu )
,dependingone xtentofdys pl asia.As soc i
ate dwi thHPV- 16a ndHPV- 18, whi ch
koilocytes in an image
used in UWORLD.
pr
oduc eboththeE6g enep r
oduc t(inhibi
tsTP5 3)a ndE7g enep ro duc t( inhi b itsp Rb )( 6be fore7;
PbeforeR).KoilocytsA a
e repatho gnomo nicofHPVi nf ect
io n.Ma yp ro gr es ss lowl yt oinv a sive
ca
rcinomaifleftuntreat
ed.Typica ll
ya s
ympt oma ti
c( de t
e c t
edwi t hPa ps me a r)orpr e se ntsa s
HPV is the strongest risk factor for cervical dysplasia, and if the patient
a
bno rmalvagi
na lblee
ding(oftenpos tcoit
al)
. is immunocompromised/immunosuppressed then screen regularly.
Ri
skfactor
s:multiplese
xualpa r
tne r
s( #1)
,smo king ,e ar lyc oita
r che ,DESe x pos ur e,
A koilocyte is an immature squamous cell with dense, irregularly staining
i
mmuno compromi se(e
g ,HIV,transplant)
.cytoplasm and perinuclear clearing (halo). It also has an enlarged pyknotic
nucleus where the chromatin has condensed for apoptosis (raisinoid).
I
nvas
ivec
arc
inoma Oft
ensquamouscellc
arci
noma.Paps
mearcandet
ectcer
vic
aldyspl
asi
abef
orei
tpr
ogr
ess
esto
i
nvas
iveca
rcinoma.Dia
gnosevi
acol
pos
copyandbiops
y.Lat
era
linvas
ionc
anbloc
kuret
ers
hy
dronephros
is r
enalf
ail
ure
.
Low-grade CIN has cells with nuclear atypia in the basal epithelial layer, but as it progresses it leads to expansion of immature basal cells to the epithelial surface.
Pr
imar
yovari
an Al
soknowna sprema t
ur eov arianf a ilur e.
i
nsufci
enc
y Pr
ematureat
resi
ao fova ria nfo l
licle sinwome no fr e prod uc tiv ea ge. Mos to ft
e ni diopa thi c ;
a
ssoci
at
edwi t
hc hr omos o ma la bno rma li
ti
e s( espe ciallyi nf e ma l
es<3 0y ears).Ne edk a ryoty pe
s
cree
ning.Pat
ientspr e s e ntwi ths ig nso fme no p aus ea f
te rpube rtybutbe forea ge40 .e str
og en,

LH, FSH.Estrogen is low because the gonads are not responding to the LH. This is a hypergonadotropic hypogonadism
(high LH, low E, respectively). The anterior pituitary is signaling the ovaries but there is no result.
With low estrogen, women are at risk of osteoporosis and heart disease.
Mostcommonc aus
es Pr
egnancy
,poly
cyst
icovar
iansyndrome ,o
besit
y,HPO axi
sabnor
ma l
it
ie s
/i
mma t
urit
y,pre
ma t
ure
ofanovul
ati
on ov
aria
nfail
ure
,hyperpr
olac
tinemia,thyr
oiddis
order
s,e
ati
ngdiso
rders,compet
iti
veathl
eti
cs,
Cushi
ngsyndro
me ,adr
enalins
uffic
iency,c
hromo s
omalabnor
ma l
it
ies(eg,Tur
nersyndr
ome )
.
Funct
ional Alsoknowna sexer
cis
e-i
nduceda menorr
hea .Seve
recal
ori
crest
rict
ion, ene
rgye x
pendit
ure,
hypothalami
c and/ors
t r
ess functi
onald i
sr
up t
ionofpulsat
il
eGnRHs e
cret
ion LH, FSH,estr
ogen.
amenor r
hea Pathogenesi
sinc
ludes lepti
n(dueto f
at)and c o
rti
sol(
str
ess,e
x ce
ssiv
ee xer
cis
e).
Associ
ate
dwi theat
ingdiso
rdersand“fe
ma lea t
hle
tet
ria
d”( c
alori
ea va
ilabi
lit
y/
exces
siv
ee x
erc
ise
,
bonemi ner
aldens
ity
,me nst
rualdys
function)
.
Polyc
ysti
covar
ian Als
ok nowna sStein-Le ventha lsyndrome .Hy perinsulinemiaa nd/orinsuli
nr es
is
tance
syndrome hypot hesizedtoa lt
e rhypo tha l
ami chor mo nalfeedbac kres
po nse LH: FSH, andr
ogens(eg,
A t
e s
to st
erone)from t hecai nternac ell
s, rateoffoll
icula rmaturat
ion unrupt
ur e
df ol
li
cl
es(cyst
s)
+a no vulati
on.Commo nc aus eo f fe rt
ili
tyinwo me n.
Enlarged, bil
ateralcy st
icov aries
;p r
e s
e ntswitha menor rhea/
oligome norrhea,hi
rsuti
sm A,a cne,
f
er t
ili
ty.Assoc i
atedwi thobe si
ty,aca nt
ho si
sni g
ricans. r
is
kofe ndome tr
ialcancer2°to
uno ppo s
e destrogenf romr e peateda nov ulat
oryc y
cles.
Trea
tme nt:cycl
er egul at
ionv i
awe i
ghtr eduction( peripher
ale s
tronefor mati
on),OCPs( pr
ev e
nt
endome tri
alhy perplasiaduet ouno ppos ede s
trogen);clomiphene ;spi
ronolact
one,finas
ter
ide,
futami det otreathi rs
utism.
The diagnostic ratio of LH:FSH is 3:1 due to the increased Insulin. Letrozole, an aromatase inhibitor, is
used to treat breast cancer specifically in post-menopausal women. It is used off-label for ovarian
stimulation since 2001 because it has fewer side effects than clomiphene and a lesser chance of multiple
gestation. By inhibiting aromatase, it is antiestrogenic.
For PCOS patients who wish to become pregnant, Clomiphene is a selective estrogen receptor modulator
that prevents negative feedback inhibition on the hypothalamus and pituitary by circulating estrogen,
resulting in increased FSH and LH, and thus increased ovulation.
The ultrasound above (A) has red arrows pointing at the hypoechoic cystic spaces in the patient's ovary.
6
ve R E
P ROD UCT
IVE—P ATHOl
Ogy
UWORLD- Failure of ovulation is a common cause of infertility. Treatment options include the administration of drugs that act like FSH and LH. Menotropin (human menopausal gonadotropin)
therapy mimics FSH and triggers the formation of a dominant ovarian follicle. When the follicle appears mature, exogenous hCG is administered. The alpha subunit of hCG is structurally
similar to LH and therefore stimulates the LH surge by inducing ovulation.
Ovar
ianc
yst
s
Fol
l
icul
arc
yst Dis
tent
ionofunr
upt
ure
dgr
aafia
nf ol
li
cl
e.Maybeas
soc
iat
edwi
thhy
per
est
rog
eni
sm,
end
ome
tri
al
hyper
plas
ia.
Mostc
ommonov ar
ianma s
siny
oungwomen.
Thec
a-l
utei
ncys
t Oft
enbil
ate
ral
/mul
tipl
e.Duet
ogo
nado
tro
pins
ti
mul
ati
on.
Ass
oci
at
edwi
thc
hor
ioc
arc
ino
maa
nd
hy
dat
idi
form mol
es.
Ovar
ianneopl
asms Mos tcommona dne x alma ssinwome n>55y ea
rsold.Ca nbeb enignorma lig
na nt
.Aris
ef r
om
surfaceepi
thel
ium, germc ells,o
rsexcordstr
oma ltis
sue.
Ma j
o r
ityofmali
g nantt umor sareepit
heli
al(s
erousc y
stadenocar
cinomamos tcommo n).
Ri s
k
withadvance
da ge,inferti
li
ty,endometr
iosi
s,PCOS, genet
icpredis
posi
tion(eg,BRCA- 1or
BRCA-2mut ation, Lynchs yndrome ,s
tr
ongfami l
yhi st
ory)
.Risk wit
hpre vi
ouspregnancy,
histo
ryofbreas
tfee ding,OCPs ,t
uballi
gati
on.Presentswithadnexalma s
s,abdominaldiste
nsi
on,
bowe lobst
ruct
ion,p leuraleffusi
on.Mo ni
torres
po nsetothera
py/rel
apsebyme asuri
ngCA1 25
l
e vel
s(notgoodf orscreening).
Ser
ouscy
sta
denoma Mos
tcommonov
ari
anne
opl
asm.Li
nedwi
thf
all
opi
ant
ube–l
ik
eep
ithe
li
um.Of
tenbi
la
ter
al.
Muci
nous Mul
ti
loc
ula
ted,l
arg
e.Li
nedbymuc
us-
sec
ret
inge
pit
hel
ium A.
c
yst
adenoma
Maturec
y s
tic Germcellt
umo r
,mo stcommonov ar
iant umorinfemale
s10–30yearsold.Cysti
cmassc
ontai
ning
t
erat
oma e
lementsf
rom al
l3g er
ml ay
ers(e
g,teeth,hai
r,seb
um)B.Ca npresentwit
hpa i
n2°toovar
ian
(
dermoidcyst) e
nlar
gementortors
ion.Amono der
ma lform wit
hthyroi
dtiss
ue(st
rumaov ari
i)unc
ommonly
p
rese
ntswithhyper
thyroi
dis
m C.Ma l
ignanttra
nsfor
ma t
ionrar
e(usuall
ytosquamouscel
l
c
arci
noma).
Sertoli-Leydig cell ovarian tumors present as an adnexal mass with amenorrhea and virilization (hirsutism, deep voice)
due to increased testosterone. Patients are usually young women. Histology similar to Sertoli cell testicular neoplasms.
F
ibr
oma Bundl
esofspi
ndle-
sha
pedfibr
obl
asts
. —t
ri
adofov
ari
anfib
roma
,as
cit
es,p
leur
al
ef
fus
ion.“
Pulli
ng”sens
ati
oningroi
n.
Sert
oli
-Ley
digc
ell Small
,g r
eytoyel
low-br
o wnma s
s.Res
embl
estes
ti
c ula
rhist
ologywi
tht
ubul
es/
cor
dsl
ine
dbypink
tumor Sert
olicel
ls
.Ma yproduceandrog
ens
viri
li
zat
ion(eg,hir
suti
sm,mal
epat
ter
nbal
dness
,br
eas
t
at
rophy,cl
it
ora
le nl
arg
e ment,o
lig
omeno
rrhea/
ame norr
hea)
.
Thec
oma Li
keg
ranul
osac
ellt
umors
,maypr
oduc
ees
tr
oge
n.Us
ual
lypr
ese
ntsa
sab
nor
malut
eri
neb
lee
ding
i
napost
menopaus
alwo
ma n.
Br
ennert
umor Res
embl
esbl
add
erepit
heli
um (t
rans
it
iona
lcel
ltumo
r).Soli
dtumorthati
spal
eye
llo
w-t
ana
nd
a
ppea
rsenc
aps
ula
ted.“Coff
eebean”nucl
eio
nH&Es t
ain.Usua
llybe
nign.
A B C
<-- High magnification micrograph of a Brenner tumor

showing the coffee bean nuclei on H&E stain.
RepRoduct ive R E
PRODUC
TIVE
—P A
T Ogy S
HOl ecti oNi i
i 6
33
Ovar
ianneopl
asms(
cont
inue
d)
Serous Mos
tcommo
nma
lig
nantov
ari
anne
opl
asm,
fre
que
ntl
ybi
lat
era
l.Ps
ammomabodi
es.
cyst
adenoc
arc
inoma
Muci
nous Rar
ema li
gnantmuci
nousov
ari
ane
pit
hel
ialt
umor
.Maybemeta
sta
ticf
rom a
ppendic
ealorothe
r
c
yst
adenoc
arc
inoma GIt umors.
Ca nr
esul
tin —i
ntr
ape
rit
oneala
ccumula
tionofmucinous
mater
ial
.
Dy
sger
minoma Mostc
ommoni
nadole
scent
s.Equi
val
entt
omalese
minomabutr
are
r.1
%ofa
llovar
iant
umo r
s;
3
0%ofger
mcel
ltumors
.Sheet
sofunif
orm“
fri
edegg”c
ell
sD.hCG,LDH=t umormark
ers.
I
mma
tur
eter
atoma Aggres
si
v e
,cont
ainsf
etalt
iss
ue,
neur
oectod
erm.Commo nl
ydi
agno
sedb
efor
eag
e20.
Typi
cal
ly
Much worse than the benign mature teratoma. r
e pr
esente
dbyimma ture
/embr
yoni
c-l
ik
ene ur
alt
is
sue
.
Yol
ksact
umor Al
soknowna sov
arianendodermals
inustumor
.Aggre
ssi
ve,i
nov ar
iesort
est
esandsacr
ococcyge
al
a
reainyoungchildr
en.Yel
low,f
ria
ble(hemor
rhag
ic)
,so
lidmass.50%haveSchil
le
r-Duvalbodies
(
res
embleglomeruli
,bl
ackarrowinE). AFP=tumorma rk
er.
Gr
anul
osac
ell
tumor Mostcommo nma li
g nantst
roma lt
umo r
.Predomi nantl
ywo me nintheir50s.Oft
enpr
oduces
Made of granulosa and theca cells. The granulosa est
rogenand/orprog es
tero
nea ndpres
entswithpo stmenopausalbl
e e
ding,endomet
ri
al
part has small cuboidal cells in rosettes with coffee
bean nuclei. The theca cells are plump with lipid hyperpla
sia
,sexualpre c
ocit
y(inpre-a
dolesc
e nt
s),brea
stte
nde r
ness.Histo
lo howsCa
gys ll
-Exne
r
contents that give the mass a yellow color on gross
inspection. Typically unilateral with estrogen-induced bodie
s( gr
anulosace l
lsarr
angedhaphazardlyaroundc ol
lect
ionsofeosinophi
li
cfui
d,res
embli
ng
endometrial hyperplasia with risk of carcinoma. pri
mor di
alfol
li
cles,blackarr
owi n F).“
GiveGr annyaCa ll
!”
Kr
ukenber
gtumor GImal
ignancyt
hatmeta
stas
ize
stoovar
ies
mucin-
sec
ret
ings
igne
tce
lla
denoc
arc
ino
ma.
Commo nl
ypre
sent
sasbil
at
eralov
ari
anmass
es.
D E F
D- Dysgerminoma= "Fried egg" cells. hCG/LDH.

E- Yolk Sac Tumor= Schiller-Duval body
resembling a glomeruli. AFP.
F- Granulosa Cell Tumor= Call-Exner body with
eosinophilic fluid, resembling primordial follicles.
Pr
imar
ydys
menor
rhea Pa
infulmenses
,causedb
yuter
ineco
ntra
cti
onst
o b
loodl
oss
is
che
micpa
in.Me
dia
tedby
pr
ostag
landi
ns.Tre
atment
:NSAIDs.
UWORLD= A 26yo woman, G1P1, comes to the office for a routine exam. She noticed new facial hair over the past few months and thinks her voice is deeper. Her last menstrual period was 5
months ago. The patient's mother died of invasive lobular breast carcinoma at age 60. Physical exam is significant for coarse facial hair, and pelvic exam reveals clitoromegaly with a large
adnexal mass. Urine pregnancy test is negative. Pelvic ultrasonography confirms a large ovarian cyst. What is the most likely diagnosis?
Sertoli-Leydig tumor. This is a rare sex cord-stromal tumor. Microscopic exam of these tumors shows hollow or solid tubules lined by round Sertoli cells and surrounded by a fibrous stroma.
A 49yo woman, G2P2, comes to the office due to 10 months of irregular vaginal bleeding. Her last menstrual period was 3 years ago. She has a history of hypothyroidism and takes levothyroxine
daily. Ultrasound reveals a thickened endometrium and a solid left adnexal mass. Endometrial biopsy is abnormal and the patient requires surgery. Intraoperatively, the ovarian mass is yellow
and firm. Pathology reports small cuboidal cells in sheets with gland-like structures containing acidophilic material. The cells are arranged in a microfollicular pattern around a pink, eosinophilic
center. What is most likely secreted by her tumor? Estrogen. Granulosa cell tumors are primarily in postmenopausal women and this sex cord-stromal tumor contains predominantly granulosa
cells and scattered theca cells. The granulosa cells make Call-Exner bodies with a pink acidophilic (eosinophilic) center and coffee bean nuclei. Theca cells are plump with lipid contents, which
give the mass a yellow color on gross inspection. The unopposed estrogen leads to hyperplasia of the endometrial cells and glands, leading to hyperplastic cells that increase the risk of
endometrial carcinoma. In young patients, excessive estrogen could lead to prococious sexual development.
A 45yo woman comes to the office due to unintentional weight loss of 15 pounds over the past 6 months. She used to enjoy dining with friends but has become concerned about lower abdominal
pressure and feeling full very quickly. She also has epigastric pain but no dysphagia, regurgitation, vomiting, or diarrhea. Physical exam shows bilateral adnexal fullness. A pelvic ultrasound
shows bilateral complex ovarian masses with solid and cystic components. Chest xray is normal. CT scan shows stomach wall thickening and ovarian masses. What is the most likely to be seen
on histologic evaluation of the ovaries? Mucin-secreting signet cells. The ovaries are a common site of metastases, most typically from a primary gastrointestinal tract cancer. She most likely
has a Krukenberg tumor, a primary gastric cancer that has metastasized to the ovary.
6
ve R E
P ROD UCT
IVE—P ATHOl
Ogy
Ut
eri
nec
ondi
ti
ons
Pol
yp Well
-ci
rcumscri
bedcoll
ect
ionofendome t
ria
lti
ssuewi
thi
nute
rinewa
ll.
Maycont
ains
mooth
musclece
lls
.Cane xt
endintoendometr
ialcavi
tyi
nthef
ormofapoly
p.Maybeas
ympto
matico
r
pr
esentwit
hpa i
nle
ssabnormalute
rinebl
e e
ding.
Adenomyos
is Exte
nsionofend omet
ria
lti
ssue(gl
andul
ar
)int
outeri
nemy ometr
ium.
Ca us
edbyhy pe
rpl
asi
aof
basa
llayerofendometr
ium.Prese
ntswit
hdysmenorr
hea,AUB/HMB,unifor
ml ye
nlar
ged,s
oft
,
gl
obularute
r us
.
Tre
atme nt
:GnRH a goni
sts
,hyst
ere
ctomyorex
cis
ionofano r
gani
zedade
nomy oma.
As
her
mans
yndr
ome Adhe
sionsand/
orfib
ros
iso
ftheendome
tri
um.Pres
ent
swi
th f
ert
il
ity
,rec
urre
ntpr
egnanc
ylos
s,
AUB,pelv
icpain.Oft
enass
oci
ate
dwit
hdila
tio
nandcur
ett
ageofint
raut
eri
necav
ity
.
L
eiomy
oma(
fibr
oid) Mostcommont umori nfemales.Oft
enp r
esentswithmultipl
edis
c r
etet
umo rsA. i
ncidencein
Afri
canAme ri
cans.Benig
ns moothmus cl
et umor;ma l
ignantt
ransf
ormatio
ntolei
omy osar
comai s
rar
e.Estr
ogensensit
ive
—tumors ize withpr e
g na
ncyand wi
thme nopause.
Peakoccurrenceat
20–40yearsol
d.Ma ybea s
ympt omat
ic,causeAUB,o rresul
tinmiscar
ria
g e
.Sever
ebleedingma y
le
adtoirondefic
iencyanemia.Whorledpa t
ternofsmoothmus cl
ebundleswithwell
-dema r
cate
d
border
sB.
Endometri
al Abnormalendome t
rialgl
andproli
fera
ti
onusuallycaus
edbye x
c es
sest
rogenst
imulat
ion. ri
skfo
r
hyper
plas
ia endome t
ri
alcar
cinoma ;nucl
earat
y pi
aisgr
eaterri
skfac
tortha ncomplex(v
ssimple
)arc
hite
ctur
e.
Pres
entsaspost
me nopausalva
ginalbl
eedi
ng. Ris
kfact
orsincludeanovula
torycy
cles
,hormone
repl
ace
me ntther
ap y
, po
lycys
ti
covaria
nsyndrome ,gr
anulosacellt
umo r.
Endometri
al Mostcommong ynec o
logi
cma li
gnancyC.Pr esentswithirr
egularvagi
na lble
eding.Twotypes
:
car
cinoma —mos tcommo n.Ass
ocia
tedwi t
huno pposedest
rogene x
pos ur
ea ndendometri
al
Early menarche and late menopause
hyper
plasi
a,usuall
yinpe ri
menopausalwo men.Ri skfa
ctor
sincl
ud eobe si
ty
,DM, HTN, i
nfert
il
it
y.
extend the reproductive time frame of Hist
olo
gys howsabno rmall
yarr
angede ndometria
lg la
nds.Ea r
lypatho g
e ni
ce ve
ntsinc
ludelos
sof
when estrogen is high. Nulliparity means
there was no moment when PTENo rmisma t
chr epa
irpro
tei
ns.
progesterone, the protective hormone, —a ss
o c
iate
dwi thendome t
ri
alat
ro phyi
npo stme nopaus
alwo me n.Aggress
ive.
Cha r
act
eriz
ed
was high.
byfor
ma ti
ono fpapil
laeandtuft
s.TP53mut at
ionsc ommo n.
Endomet
ri
ti
s Infamma t
ionofendome tr
ium D associ
ate
dwi t
hr e
tai
nedprod
uc t
sofconc
epti
onfol
lowi
ngdeli
ver
y,
miscar
ri
age,abor
ti
o n,orwi t
hforei
gnbod y(e
g,IUD).Reta
inedma t
eri
ali
nuter
uspromote
s
inf
ecti
onbyba c
ter
ialfo r
af r
omv aginaorint
est
inalt
rac
t.Chroni
cendometr
it
ischa
ract
eri
zedby
pres
enceofplas
mac e
llsonhi s
tol
ogy.
Trea
tment:gent
amicin+c lindamycn+/
i −ampici
lli
n.
Endomet
ri
osi
s No n-neop l
asti
ce nd ometri
um-likeglands/
str
omao utsidee ndome t
rialc a vi
ty.Canbefound
any whe re
;mo s
tc ommo ns i
tesareovary(fr
equent lyb i
later
al)
,pelvis, perit
oneum (ye
llow-brown
“po wderbur n”lesions)
.Inova r
y,appearsasendo me t
ri
o ma( bl
ood- fil
le d“chocol
at
ec yst
s”
[ovalstructuresabov eandbelowa ster
isk
sin E]) .Ma yb ed uetore trog ra
defow,me taplast
ic
transf
o rmat i
ono fmul t
ipot
entc ell
s,tr
ansport
ationofe ndome tr
ialtissuev ialymphat
icsy s
tem.
Cha ract
e ri
zedbyc ycl
icpelvi
cpa in,ble
eding,dysme norrhea,dyspare uni a
,dyschez
ia(painwith
de f
ecation),inf
ertili
ty;
norma l-
sizeduterus
.
Treatme nt:NSAI Ds ,conti
nuousOCPs ,proges
tins ,GnRHa goni
sts,da nazol,l
apa
roscopicremoval
.
A B C D E
A & B -- Leiomyoma tumors and wholred patterns of smooth muscle. C -- Endometrial carcinoma D -- Endometritis E -- Endometriosis Chocolate cysts
UWORLD- Subserosal fibroids demonstrate exaggerated irregularity compared to other types of fibroids, which are more constrained by uterine
tissue. Irregular uterine enlargement from fibroids can put pressure on adjacent organs, causing bulk-related symptoms. Fibroids on the posterior
uterus can put pressure on the colon, leading to constipation. Patients may be able to relieve the pressure by "splinting" to defecate, which
involves manual deflection of the obstruction. Some posterior fibroids can displace the uterus upward and cause obstructive urinary symptoms.
To the left is another histological image of the whorled pattern of smooth muscle in fibroids.
With endometriosis, remember the fact that it is frequently bilateral with yellow-brown "powder burn"
lesions. In the ovary, it will appear as blood-filled "chocolate cysts"
Endometriosis has endometrial tissue in both ovaries, pelvis, and peritoneum.
Adenomyosis (left) has glandular endometrial tissue in the uterine myometrium, so there is AUB.
With leiomyoma (fibroids) below, remember that it has a whorled pattern of smooth muscle bundles.
UWORLD= A 42yo woman, G4P4, comes to the clinic
due to heavy and painful menstrual bleeding over the
past 3 months. Her last menstrual period was 4 weeks
ago. Menarche was at age 10, and menstrual periods
last for 3-5 days and occur every 30 days. She is sexually
active with her husband and does not have pain with
intercourse. She had a bilateral tubal ligation 3 years ago
after the birth of her last child. She takes no medications
and has no allergies. BMI is 24. Vital signs are normal.
On bimanual examination, the uterus is uniformly
enlarged. Urine bhCG is negative. Biopsy shows
secretory endometrium. What is the most likely cause
of her symptoms?
Endometrial tissue in the myometrium (43%) while 22%
chose hyperplastic growth of tissue from endometrial
surface. Adenomyosis is the presence of endometrial
glandular tissue within the myometrium. It is common
in middle-aged parous women and symptoms include
heavy menstrual bleeding and dysmenorrhea (menstrual
cramps). This patient's endometrial biopsy result of
secretory endometrium is a normal finding for a woman
in day 21 of her menstrual cycle. Adenomyosis can only
be diagnosed definitively by microscopic examination of
a hysterectomy specimen.
UIWORLD= A 28yo nulliparous woman comes to the clinic to be evaluated for infernitility. She has been having unprotected intercourse with her husband for the past 12 months and
experiences pain with deep vaginal penetration. Menarche was at age 11 and her period occurs every 26 days and lasts 5-7 days. Her menstrual cycles are accompanied by moderate to
severe lower abdominal pain. Pelvic exam shows a normal-sezied, retroverted uterus. The posterior vaginal fornix is very tender to palpation. Her condition most likely involves what?
Ectopic endometrial tissue. Endometriosis. Nulliparity, early menarche, and prolonged menses are all her risk factors for endometriosis. In contrast, multiparity, extended lactation, and late
menarche decrease the risk due to less frequent menstrual cycles. Bleding and shedding of extrauterine endometrium leads to formation of blood collections in the ectopic locations. Over
time, the blood undergoes hemolysis and induces inflammation, which is followed by adhesion formation, which in turn distorts organ structure and function (her retroverted uterus).
The adhesions may lead to infertility and infiltration of the posterior cul-de-sac may cause painful intercourse and dysmenorrhea.
A- Mucinous cystadenocarcinoma would not have endometrial hyperplasia because it

produces mucin, not estrogen. This malignant neoplasm originates from the ovarian
surface epithelium.
B- A dysgerminoma is the ovarian equivalent of the testicular seminoma. These do not
secrete estrogen either, so there would be no endometrial hyperplasia.
C- Benign cystic teratomas (dermoid cysts) can have skin, cartilage, bone, and teeth.
They do not secrete estrogen but may secrete thyroid hormone via struma ovarii.
E- Fallopian tube carcinoma is exceedingly rare.
RepRoduct ive R E
PRODUC
TIVE
—P A
T Ogy S
HOl ecti oNi i
i 6
35
UWORLD= A 39yo Caucasian female presents to your office with a palpable nodularity in the right breast. Pathologically, the lesion is composed of ducts distended by pleomorphic cells with
prominent central necrosis. The lesion does not extend beyond the ductal basal membrane. What is the most likely diagnosis in this patient? Comedocarcinoma (40%) while 20% chose
mammary duct ectasia. The typical histological picture of comedocarcinoma (DCIS) is described. Mammary duct ectasia is characterized by ductal dilation, inspissated breast secretions, and
chronic granulomatous inflammation in the periductal and interstitial areas.
Br
eas
tpat
hol
ogy
Ni
ppl
e L
act
i
fer
ousd
uct Ma
jor
duc
t Ter
minald
uct
l
o b
ular
unit S
tr
oma
I
nt
rad
uctal
papi
ll
oma Fi
brocy
sti
cch an
ge
A
bsce
ss/
ma s
ti
ti
s Fib
roa
denoma
DCIS
P
agetdi
sea
se Phyl
lo
destu
mor
LCI
S
Ducta
lcar
cinoma
Lobul
arcar
ci
n oma
Beni
gnbr
eas
tdi
seas
es
F
ibr
ocys
ticc
hange
s Mos tc ommo ninp r
eme nopa
usalwome n2 0-
5 0year
so l
d.Pr e
sentwit
hpre mens t
rualbrea
stpain
orlumps ;oftenbil
ate
ralandmul ti
focal.Nonp r
olif
era
tivelesi
onsincl
udesimp lecyst
s(fuid-
fil
led
duc tdi l
ation,bl
uedo me)
,papill
arya pocr
inec hange/
me tapla
sia
,str
omalfibrosis
.Riskofcanceris
usua llyno tinc
reas
ed.Subtypesinclude:
—a ci
niands tromalfibros
is,a
ssocia
tedwithcalci
fica
tions.Sli
ght ri
skfor
ca nc e
r.
—cell
sinte rminalduc t
alorlobularepi
thel
ium. ri
skofc arci
nomawi th
aty picalcell
s.
I
nfammatory —be nign,
usual
lypainl
ess
,lumpduet oi
njur
ytobreas
tt i
ssue.Cal
cifie
do i
lcyston
proces
ses mammogr
aphy;necr
oti
cfatandgia
ntc e
llsonbi
opsy
.Upto50 %o fpa t
ie
ntsma ynotreporttra
uma.
—occur
sd uri
ngbreast
feedi
ng, ri
skofba
c t
eri
a linfe
cti
ont hroug
hc racksin
ni
ppl
e.Sa
ureusismostco
mmonpa thogen.Tr
eatwi
thanti
biot
icsa ndconti
nueb reas
tf
e eding.
Beni
gnt
umor
s —mos tc o
mmo ni nwo me n<3 5y ear so ld.Sma ll, we ll-d efine d, mo bi l
ema s
sA.
Histologically (4th image below), fibroadenomas are
characterized by a benign-appearing cellular or
s
izeandte
ndernesswit
h e strog en( e g ,pregna nc y,pr i ort ome ns trua tion) .Ri skofc anc eri s
myxoid stroma that encircles epithelium-lined usuall
ynoti
ncre
a s
ed. Usually regress after menopause. Histologically characterized by a benign-appearing cellular or
myxoid stroma encircling epithelium-lined glandular and cystic spaces.
glandular and cystic spaces (red arrow).
—s mallfib ro epit he lialtumo rwi thi nl ac ti
fe rousduc t
s, typ ica l
l ybe nea tha re o la.
Mos tc
ommo ncauseofnippl
edi scha rge( ser
o uso rb lood y ).Sl ig ht riskf o rc a nce r.
—l ar
g emassB o fc onne c tiv
et issuea ndc ys tswi th“ le af-like ”lob ul ationsC. Mos t
commo nin5thdecade.Somema ybe co mema ligna nt .
Gynec
omas
tia Br
eastenlarge
me ntinma l
esdueto est
rogencompa r
edwi t
ha nd r
ogena c
tiv
ity
.Physi
ologi
c
i
nne wbo r
n, puber
tal
,ande l
derl
yma le
s,butma yper
sis
ta f
terpuberty.Otherca
usesi
nc l
ude
ci
rr
hosis,hypogonadi
sm( eg,Kli
nefe
lt
ersyndrome),t
est
icula
rt umo r
s,anddrugs(Spi
ronol
act
one,
Hormo nes,Cimeti
dine,Finast
eri
de,Keto
c ona
zo l
e So
:“ meHo rmonesCr ea
teFunnyKnoc ke
rs”
).
A B C Fibroadenoma from a UWORLD question.

6
ve R E
P ROD UCT
IVE—P ATHOl
Ogy
UWORLD= A 51yo woman comes to the office for a follow-up visit three weeks ago, she had a screening mammogram that was suspicious for malignancy. An ultrasound-guided needle aspiration
showed invasive ductal carcinoma. The patient underwent a lumpectomy with axillary dissection and has no metastatic disease. Immunohistochemical analysis was positive for estrogen,
testosterone, and human epidermal growth factor receptor 2. Adjuvant therapy with monoclonal antibody is going to target what? The tyrosine kinase receptor. The patient has 3 different
receptors, but the HER2 (Human Epidermal growth factor Recptor) receptor is targeted by trastuzumab. HER2 works via the transmembrane tyrosine kinase, so trastuzumab binds that and
downregulates it, promoting apoptosis.
Br
eas
tcanc
er Co mmo nlypos tme nopa usal.Of t
enp res
e ntsas Ri s
kf a
c t
o r
sinwo me n: ag e
;hist
oryof a
typic
a l
HER-2/neu (c-erbB2) is on chromosome 17 apa l
pa b l
eha rdma ssmos to fte
ni ntheuppe r hyperplasi
a;f
a mi lyhist
ory( ris
kwith numb er
and it is a proto-oncogene that can have a
gain of function mutation, making it an outerqua drant.Invasi
v ec ancerca nbec ome ofcloserrel
at
ivesa t
young e
ra ge)
;ra
ce( Caucasia
ns
oncogene. It's gene product is a receptor fix
edt ope ct
o r
almus cles,deepf asci
a,Coo pe r a thighe s
tris
k, Af ri
canAme ri
cansat ris
kfor
tyrosine kinase and it is associated with
breast and gastric carcinomas. l
i ga
me nts,andov er
lyings kin nipple tr
iple⊝ b rea
st ca ncer
);BRCA1o rBRCA2g ene
BRCA1/BRCA2 are tumor suppressor genes, r etr
actio n/s
kindi mpl i
ng .De rma llympha tic mut ati
ons; estrogene xposure(eg
, null
ipari
ty)
;
so a loss of function of both alleles will lead invas
io n l
y mp hedema thickenedsk i
n postm enopausal o bes
ity(a
d i
poseti
ssue convert
s
to cancer. BRCA 1 is on chromosome 17 also,
but BRCA2 is on chromosome 13. It's gene arounde xagg er
atedha i
rfo l
li
c l
es peau androstenedi
o net oe s
trone); tot
alnumb erof
product is a DNA repair protein and it is
associated with breast, ovarian, and d’or
ang e(“orangepe e
l”)a ppe ar
anc e. me nstr
ua lcycl
e s;absenceo fbre
astf
e e
ding;late
r
pancreatic cancers. Usuallya rise
sf r
omt ermi nalduc tlobula
runi t
. ageo ffir
stpr
e gna ncy;alcoholconsump ti
on.In
Angiosarcoma (pg 503) is a blood vessel Ampl ificati
on/ove r
ex press
ionofe st
rogen/ me n:BRCA2mut at
ion,Klinefel
t
ers yndro
me .
malignancy of the head, neck, and breast.
It usually occurs in the elderly on sun-exposed progester one r
ece pt
o r
s or c-e
rbB 2 (
H ER2 ,an Axill
ary lymph no de metastasi
sisthe mo s
t
areas, but it is associated with radiation and E GFr e ceptor)iscommo n;ER⊝,PR⊝,a nd impor tantprog nos t
icfactorinearly-st
age
chronic postmastectomy lymphedema.
HER2 /ne u⊝ f orm mo rea ggress
ive. disease.
T
yPE C
HAR
ACT
ERI
ST
ICS N
OTE
S
Ductal
car
cinomai
n Fil
lsduc
tallumen(bl
ackarr
owi nA indicat
es Ear
lyma li
gnancywit
houtbasementme mbrane
s
itu neopl
ast
iccell
sinduc
t;bl
uea rr
owshows pe
ne tr
ati
on.Usual
lydoesnotpr
od uceama ss
.
engor
gedbloodves
sel
).Ari
sesfr
om ductal —SubtypeofDCI S. Cel
ls
aty
pia
.Of t
enseenear
lyasmi c
roca
lci
fic
ati
ons ha
v ehigh-
gradenucl
eiwit
he xt
ensivecent
ral
onma mmog ra
phy. ne
c ro
sisB anddyst
rophi
cc a
lci
fic
a t
ion.
Pagetdi
seas
e Ext
ensionofunderl
yi
ngDCI S/
inv
asiv
ebreas
t Pa
getcel
ls=i
ntr
aepi
the
li
ala
deno
car
cino
ma
c
ance rupthela
cti
fer
ousduct
sandintothe ce
lls
.
c
ontiguousski
nofnippe
l e
czematous
pa
tche sov
erni
ppleandare
olars
kinC.
L
obularc
arc
inomai
n Doe
snotproduc
ema ssorcal
ci
fic
ati
ons r
is
kofc
a nc
eri
nei
the
rbrea
st
s
itu
inc
identa
lbiops
yfindi
ng. (
vsDCIS,s
amebr
eas
tandquadr
ant
).
I
nvas
iveduc
tal Fi
rm,fibr
ous,“
rock
-har
d”masswit
hsharp Subt
ypes:tubul
ar—well
-dif
fer
enti
ate
dtubul
es
ERRATA - The subtypes part refers to all marg
insandsma l
l,g
land
ula
r,duct
-l
ik
ecell
sin t ha
tlackmy oe
pit
heli
um; mucinous—ab
undant
invasive carcinomas, not just invasive
ductal. de
smo pl
ast
icst
roma. ext
rac
ellula
rmuc i
n,se
e ninolde
rwome n.
I
nvas
ivel
obul
ar
E-cadheri
nexpress
ion or
de r
lyr
owo fce
lls Oft
enbila
ter
alwi
thmulti
plel
esi
onsi
nthes
ame
(
“si
ng l
efil
e”D)a ndnoductformat
ion.Oft
en l
ocat
ion.
l
acksdesmopl
a s
ti
cr es
pons
e. Li
nesofcell
s=Lobul
ar.
Medul
lar
y La
rge,anapl
ast
icc
ell
sgro
wingi
ns he
etswit
h We ll
-ci
rcumsc
ribe
dtumorc
anmi
mic
a
ssoc
iate
dlymphocyt
esandpl
asmacell
s. fibr
oadenoma.
I
nfammat
ory I
nvas
ionofder
ma ll
ymphati
cspa
ces
pai ul Poo
nf rprog
nosis(
50%survi
valat5yea
rs)
.
br
eas
twithwarm,swol
len,e
ryt
hema
toussk
in, Of
tenmist
akenformast
it
isorPag
etdis
eas
e.
pe
aud’or
angeE. Us
uall
ylack
sapa l
pab
lema s
s.
A B C D E
A -- DCIS (Black; neoplastic cells in duct) (Blue; engorged blood vessel)

B -- Comedocarcinoma High grade nuclei with extensive central necrosis and dystrophic calcification.
C -- Paget disease eczematous patches over nipple and areola.
D -- Invasive lobular orderly "sginle file" row of cells and no duct formation.
E -- Inflammatory invasive carcinoma peau d'orange.
RepRoduct ive R E
PRODUC
TIVE
—P A
T Ogy S
HOl ecti oNi i
i 6
37
Peni
lepat
hol
ogy
Peyr
oni
edi
sea
se Abnormalcurva
tur
eofpenisA duetofibro
uspla q
uewithintunic
aa l
buginea.Ass
ocia
tedwi
th
A e
recti
ledysf
uncti
on.Cancausepain,anxi
ety.Consi
dersurgi
calrepai
rortre
a t
mentwith
c
ollage
na s
einj
ecti
onsonc
ec urv
aturesta
bili
zes.Dis
ti
nctfrom penil
efr
acture(r
uptur
eofcor
por
a
c
a v
ernosaduetofor
cedbending
).
I
schemi
cpr
iapi
sm Pa
infuls
ustai
nederect
ionlas
ting>4hours.As
soci
at
edwithsi
ckl
ec el
ldis
ease(
si
ckl
edRBCs
bl
ockvenousdrai
nageofcorpuscav
ernos
um vas
cula
rchannel
s)
,me di
cat
ions(
eg,s
il
denafil
,
t
razodone
).Tre
atimme dia
tel
ywithcorpo
rala
spi
rat
ion,
intr
aca
vernosa
lphenyl
ephr
ine,orsurg
ica
l
dec
ompr e
ssi
ontop r
eventi
schemia.
Squamouscel
l Seeni
nt heUS,butmorecommo ninAsia,Afr
ica
,So uthAme ri
ca.Prec
ursori
nsitule
sions:
car
cinoma Bowendise
ase(i
npeniles
ha f
t,p
res
entsasle
ukoplakia“whit
eplaque”)
,eryt
hropl
asi
aofQue yrat
B (
carc
inomainsit
uoftheglansB,prese
ntsaseryt
hroplaki
a“redp l
aque”)
.Bowenoidpapulosi
s
(
carc
inomainsit
uofunc l
earmali
gnantpote
ntia
l,present
ingasreddi
shpapules
).Ass
oc i
at
edwi t
h
unci
rcumcis
edma l
esandHPV.
Bowen disease
<-- Erythroplasia of Queyrat presenting with
Bowenoid Papulosis --> leukoplakia.
Cr
ypt
orc
hidi
sm Des
c entf
ail
ureofoneA o rbothte
stes
;impai
redspermatogenesi
s(s
incesperm devel
opbe s
tat
A t
empe ra
tur
es<3 7°C);c
anha venormaltes
tos
ter
onel ev
els(Leydi
gc e
llsaremos t
lyunaf
fect
ed
b
yt empera
ture
);ass
ocia
tedwith r i
skofger
mc elltumors.Pre
ma tur
it
y r iskofcryp
tor
chidi
sm.
inhibi
nB, FSH, LH; te
stos
ter
one inb i
lat
eralcry
ptorchi
dism,no r
ma linunil
ater
al.
T
est
icul
art
ors
ion Rot
ati
onoft
est
icl
ear
ounds
per
mat
icc
orda
ndv
asc
ula
rpe
dic
le.Co
mmonl
ypr
ese
ntsi
nma
les
The gonadal arteries arise from the abdominal aorta
slightly below the renal arteries. They course down 1 2–18yea r
sold.Ma yoccuraft
e ranincit
inge ve
nt(eg,t
rauma )orspont
a neousl
y.Chara
cter
ize
d
obliquely and laterally within the retroperitoneal byac
ute,sever
ep ai
n,high-r
idingtesti
s,andabsentcremast
ericrefex.
space near the psoas major muscle. The right one
travels in front of the IVC and behind the ileum, the T r
eat
me nt:sur
gicalc
o r
rect
ion(o r
chiopexy
)wi thi
n6ho urs,manua ldet
orsio
ni fsur
gic
alopt
ion
left one courses behind the left colic and sigmoid
arteries. After crossing anteriorly over the ureter, they unav
ail
ab l
e i
n t
imefra
me .Ifte
stisisnotvia
b l
e,orc
h i
ect
omy .Orch i
opexy,when per
for
me d,
run parallel to the external iliac vessels and traverse shouldbeb il
ater
albecausethec ont
ralat
eralt
e s
ti
sisatri
skforsubsequenttors
ion.
the inguinal canal. Inadequate fixation of the lower
pole of the testis to tunica vaginalis leads to torsion.
Var
icoc
ele Di
latedv e
insinpa mp i
nifo
r mp l
exusdueto v enouspressure;mos tcommo nc auseofscr
ota
l
A e
nlargeme ntinad ul
tma les;
mo stof
tenonleftsi
debe c
a useof r esis
tancetofowf r
o mleft
g
ona dalveindrainageintolef
trenalvei
n;canc a
useinfertil
itybec a
useof temperat
ure;
di
agno se
db ystandingclinic
alexam/Valsa
lvama neuver(dist
e nsi
ononi nspect
ionand“ bag
o
fwor ms ”onpa l
pa t
ion;augmentedbyVa l
salva
)orultrasoundwi thDop plerA; doesnot
t
ransil
lumina t
e.
Tr
eatme nt:cons
idersurgi
ca ll
iga
tionorembo l
izat
ionifassociatedwithpaino ri
nfert
ili
ty
.
6
ve R E
P ROD UCT
IVE—P ATHOl
Ogy
Extr
agonadal
ger
mcel
l Ar
is
einmidli
neloc
ati
ons.I
na d
ults
,mo s
tcommonl
yinre
troperi
toneum,medi
ast
inum,pine
al,a
nd
tumors s
upra
sel
larr
egi
ons
.Ininfa
ntsandyoungchi
ldr
en,
sac
roc
oc cy
gea lt
era
toma
saremostcommo n.
Sc
rot
almas
ses Be
nig
nscrot
all
esi
onspr
ese
nta
ste
sti
cul
arma
sse
stha
tca
nbet
rans
il
lumi
nat
ed(
vss
oli
dte
sti
cul
ar
t
umors
).
Congeni
tal
hydr
ocel
e Commoncaus
eofscro
talswel
li
ngA i ni
nfa
nts
, Tr
ans
il
lumi
nat
ings
wel
li
ng.
A
d
uetoi
ncomple
teobli
ter
ati
onofproces
sus
v
agi
nal
is
.Mostspo
ntaneous
lyres
olveby1yea
r
o
ld.
The communicating hydrocele is a collection of peritoneal fluid within the tunica vaginalis.
Ac
qui
redhydr
ocel
e Sc
rota
lfui
dcol
lect
ionusua
lly2°t
oinf
ecti
on,
t
rauma,t
umor
.Ifbl
o ody hema
toce
le.
Sper
mat
ocel
e Cys
tduet
odi
la
tede
pidi
dyma
lduc
torr
ete Pa
rat
est
icul
arfuc
tua
ntno
dul
e.
t
est
is
.
T
est
icul
arger
mcel
l ∼95%o fal
lte
sti
cul
artumors.Mostof
tenoc
curinyoungme n.Ris
kfac
tor
s:c
rypt
orc
hidi
sm,
t
umors Kli
nef
e l
te
rsyndr
ome. Canpres
entasamixedge
rmc el
ltumo r
.Donottr
ansi
ll
uminat
e.Us
ual
ly
notbi
opsi
ed(ri
skofs
ee di
ngscr
otum),r
emovedvi
aradi
calorchi
ect
omy.
Semi
noma Mali
gnant;pa
inl
ess,
homogenoust
est
icula
renl
argement
;mostcommontes
ti
cula
rtumor.
Doesnot
occ
urininfa
ncy.Larg
ecel
lsinl
obule
swi t
hwater
ycyto
plas
ma nd“f
ri
edegg”appe
ara
nce.
pla
cent
al
ALP(PALP).Highlyr
adi
osens
it
iv
e.Latemeta
sta
sis
,exc
ell
entpr
ogno
sis
.Si
mila
rtodys
germi
nomain
f
ema l
es.
Yol
ksact
umor Al
soknownast
est
icul
arendoder
ma ls
inust
umor.Yell
ow,muc i
nous
.Aggress
ivemali
gna
ncyo
f
t
est
es,
anal
ogo
ustoovari
anyolksa
ctumor.Sc
hill
er-Duvalbodi
esr
esembleprimi
tiv
egl
omer
uli
.
AFPishi
ghl
ycha r
act
eri
st
ic.Mostcommontest
icula
rtumo ri
nboys<3y earso
ld.
Chor
ioc
arc
inoma Mali
gnant
, hCG.Disor
deredsyncy
tiot
rophobla
sti
candc y
tot
ropho
bla
sti
cel
ement
s.
Hemat
ogenousmet
ast
ase
stolungsandbrain.Ma ypr
oducegyneco
ma s
ti
a,s
ympt
omsof
hy
pert
hyroi
dis
m(α-s
ubunitofhCGi si
dentica
ltoLH, FSH,TSH).
T
erat
oma Unl
ikei
nfe
mal
es,Ma
tur
ete
rat
omai
na tMa
dul le ybeMa
sma li
gna
nt.Be
nig
ninc
hil
dre
n.
E
mbr
yonal
car
cinoma Mali
gnant
, he morrhagi
cmasswithnecros
is;pa
inful;wor
seprog
nosi
sthanse
mi no
ma.Oft
en
gl
andul
ar/pa pi
ll
arymorpho
logy.“Pur
e”e mbryonalcar
cinomaisr
are;mos
tcommonlymixe
d
wit
hothert umort y
pes.Maybea s
soc
iate
dwi t
h hCG andnormalAFPlevel
swhenpur
e(AFP
whenmixe d).
Hor
monel
evel
singer
mcel
ltumor
s
S
EmI
NOmA y
OlKS
ACT
UmO
R C
HOR
IOC
ARC
INO
mA T
ERA
TOmA E
mbR
yON
AlC
ARC
INO
mA
PAL
P – – – –
AF
P – – – –/(
whe
nmi
xed)
β-
hCG –/ –/ –
High magnification view of seminoma, which is composed of clear cells.

The cells have visible nuclei prominent nucleoli and clear cytoplasm.
Actually looks like a bunch of semen swimming to the right.
RepRoduct ive R E
PRODUC
TIVE
—P A
T Ogy S
HOl ecti oNi i
i 6
39
T
esti
cul
arnon–ger
m 5
%ofa
llt
est
icul
art
umor
s.Mos
tl
ybe
nign.
c
ell
tumors
L
eydi
gcel
ltumor Gol
denbro
wnc ol
or;cont
ainsReink
ec r
yst
als(
eosi
nophi
li
ccyt
opl
asmici
ncl
usi
ons
).Pr
oduc
es
a
ndrog
ensore
str
og e
ns gyne
coma s
ti
ainme n,pre
coci
ousp
ubert
yinboy
s.
Ser
tol
ice
llt
umor Andr
obl
ast
omaf
roms
exc
ords
tr
oma
.
T
est
icul
arl
ymphoma Mostcommontes
ti
cul
arc
anc
eri
nol
derme
n.No
ta1
°ca
nce
r;a
ris
esf
rom me
tas
tat
icl
ymp
homat
o
t
est
es.Ag
gre
ssi
ve.
Epi
didymi
ti
sandor
chi
ti
s
Epi
didymi
ti
s I
nfammat
ionofe
pidi
dymis.
Pre
sent
swit
hlocal
ize
dpai
nandtender
nessov
erpost
eri
ort
est
is.
⊕
Pre
hnsi
gn(pai
nrel
iefwi
ths
crot
ale
leva
ti
on).Mayp
rog
res
stoinvol
vete
sti
s(e
pidi
dymo-or
chi
ti
s)
.
Or
chi
ti
s I
nfammati
onoftes
ti
s.Pres
e ntswithtest
icul
arpain,swell
ing.Caus
esinc
lude
:
Ctr
achomatsa
i ndNg o
no rrhoe
a e:mostcommoni nyoungme n
Ecoia
l ndPse
udomo nas:mos tcommoni ne l
derlyme n,as
soci
ate
dwithUTIa
ndBPH
Mumpsorchi
ti
s:i nfer
tilit
yris
k ,rar
einboys<1 0y e
a r
sold
Aut
oimmune:granul
oma sinvo
lv i
ngseminif
eroustubules
B
eni
gn
Benignprostat
ic Commo ni nme n>5 0y ear
so ld. Cha racteriz
ed A
nte
ri
orl
obe p
ros
tat
i
c
h
yper
pl
asa
i
hyperpl
asia bys moot h, e
lastic,firm nod ula re nl argeme nt
Ur
et
hra
(hy perplasiano thy pe rt
rophy )o fpe r i
urethral
(latera
la ndmi ddle)l obe s
,whi chc ompr e s
sthe L
ate
ral
lob
e
ur et
hrai ntoav e r
ticals li
t.Notpr ema lignant.
Ofte nprese ntswi th f reque nc yo fur ination, Mi
ddl
elo
be
noc turi
a, di f
ficultys t
a rti
nga nds top pingur ine
stream, dy suria. Ma yl eadtodi ste nt i
o na nd P
ros
tat
eca
nce
r
P
ost
er
io
rlo
be
hy pertr
ophyo fb l
add e r,hydrone phr osis
,UTI s
.
freepros tate-specifica nti
g en( PSA) .
Trea t
me nt: α1-ant a
g oni st
s(teraz osin,
tams ulosin),whi c
hc a userela xationof
smoo t
hmus cle;5α- re ductasei nhi bitors(eg,
finaste
ride );PDE- 5i nhib i
tors( eg ,ta dalafil
);
surg i
calre section( eg ,TURP ,ab lat ion).
Pr
ost
ati
ti
s Charac
ter
ize
db ydys
uria,fr
equency,ur
gency
,lowba ckpai
n.Warm, t
ender,enla
rgedprost
ate
.
Acut
eba c
ter
ialpr
ost
ati
tis
—i nolde
rme nmostc ommo nbact
eri
um isEc o
li;i
ny oungme nconsi
der
C t
racho
ma t
is,Ngonorr
hoeae.
Chroni
cprost
ati
ti
s—e i
therbact
eri
alornonbact
e r
ial(
eg,2
°toprev
iousinfe
c t
ion,nerv
ep r
oblems,
che
mi ca
lir
rit
ati
on)
.
Pros
tat
ic Commo ninme n>5 0y ea rso ld. Ar isesmo sto f tenf ro m pos teriorlo be( pe r
iphe ralz o ne)ofpros
tat
e
adenoc
arci
noma gla
ndandismos tf
re que nt lydi ag nos edb y PSAa nds ubs eq ue ntne edl ec or eb iops ie s
.Pros
tat
ic
aci
dphosphat
ase(PAP)a ndPSAa reus e fult umo rma rk er s(t otalPSA, wi th f ract ionoffree
PSA).
Os t
eobla
sti
cme t
a stase sinbo nema yde velo pi nl ates ta ges,asi ndi cat e dbyl owe rbackpain
and serum ALPa ndPSA. Me tastas i
stot hes pineof tenoc c ur sviaBa tson( v ertebr al)venous
ple
xus. Since the metastases may be osteoblastic, alkaline phosphatase (ALP) increases.
Breast cancer has osteolytic metastases.
UWORLD= A 70yo man comes to the office due to 3 weeks of unrelenting lower back pain. He was grocery shopping when he first noticed the pain. He reports no trauma or leg weakness but
describes having to strain to urinate. He has a history of HTN and hyperlipidemia and has not seen a doctor in the past 5 years. His wife died a year ago, and he now lives alone. He is a retired
construction worker and has a history of tobacco and marijuana use. There is tenderness in the lower vertebral wall and imaging study of the spine reveals several osteoblastic lesions in the
lumbar vertebrae. What structure was most likely involved during the spread of his disease? Prostatic venous plexus (48%), while 25% chose internal iliac nodes. His new back pain, urinary
symptoms, and osteoblastic lesions on the lumbar spine suggest prostate cancer with metastases to the bone. Cancers of the pelvis, including the prostate, spread to the lumbosacral spine via
the vertebral venous plexus. The prostatic venous plexus receives venous supply from the prostate, penis, and bladder. After regional lymph nodes, liver, lungs, the skeletal system is the fourth
most common site of metases, which usually disseminate hematogenously. Although lymph nodes are the most common sites of metastasis in general, lymphatic spread to the skeletal system
is very rare. The prostate does drain to the internal iliac node, but that would not lead to metastases to the bone.
6
ve R E
P ROD UC
TIVE
—P HARmAC
OlOgy
R
EPROD
UCT
IVE
—PHA
RmAC
OlOgy
Cont
rol
ofr
epr
oduc
tivehor
mones
Hy
pot
hal
amus
v
iab
loc
ki
ngn
ega
ti
vef
eed
bac
k
Cl
omi
phe
ne + Gn
RH
Gn
RHa
nta
gon
ist
s -
Gn
RHa
gon
ist
s –
/+
Anter
ior
pi
tuit
ary
LH
F
SH
LH L
H
Ov
ary F
SH T
est
is
Or
alc
ont
ra
cep
ti
ves
Da
naz
ol -
Ke
toco
nazo
le
Dan
azol
- P
-45
0c1
7 - K
etoc
onazol
e
S
pir
onol
acto
ne
A
ndr
ost
ene
dio
ne T
est
ost
ero
ne T
est
ost
ero
ne
A
nast
ro
zole
α−r
5 edu
cta
se
-
L
etr
ozol
e - A
roma
tas
e F
ina
ste
ri
de
E
xemest
ane
E
str
iol E
str
one E
str
adi
ol Di
hyd
rot
est
ost
ero
ne
T
amoxi
fen
R
alo
xif
ene
–/
+ Androgen-r
ecept
or F
lut
ami
de
c
ompl ex - C
yprot
er
one
S
pir
onol
act
one
Geneex
pressi
on Geneexpres
sion
nes
i trogen- nandr
i ogen-
r
espons
ivecell
s respons
ivecell
s
This is a classic presentation of uterine fibroids and the patient has

leiomyoma. These benign tumors are sensitive to estrogen and wax This patient has PCOS. Acanthosis nigricans of the nipple occurred
and wayne in size proportional to estrogen levels. Menometrorrhagia, due to the insulin resistance. The LH:FSH ratio is increased and the
or heavy irregular bleeding is a common finding. bilaterally enlarged ovaries further hint PCOS.
RepRoduct ive R EPRODUCT
IVE
—PHAR mA
C Ogy S
Ol ecti oNi i
i 6
41
UWORLD= Initial use will cause a transient rise in pituitary LH secretion, which leads to a rise in testosterone levels. However, continuous use suppresses
Leupr
oli
de LH
release and leads to a decrease in testosterone production. With lesser testosterone, there will be lesser DHT production as well.
mE
CHA
NIS
m GnRHa nalogwi t
ha go
nis
tprope r
ti
es Le
upr
oli
dec
anbeus
e nl
di i
euofGnRH.
whenusedi npulsa
til
efa
shion;antag
o nis
t
pr
oper
tie
swhe nusedincontinuousfashi
on
(
downregulate
sGnRHr ece
p t
orinpituita
ry
FSHa nd LH) .
C
lI
NI
CAlU
SE Ut
eri
nefib
roids
,e ndomet
ri
osi
s,prec
oci
ous
p
ubert
y,prost
atecance
r,i
nfe
rtil
it
y.
A
DVE
RSEE
FFE
CTS Hypogona
dism, li
bid
o,e
rec
til
edy
sfunc
tio
n,
naus
ea,vomit
ing
.
Es
trogens Et
hiny
les
tr
adi
ol,
DES,
mes
tra
nol
.
mE
CHA
NIS
m Bi
nde
str
oge
nre
cep
tor
s.
C
lI
NI
CAlU
SE Hypo
gonadi
smo ro
var
ianfa
ilur
e,menst
rua
labnorma
li
ti
es(
combi
nedOCPs
),ho
rmone
r
epl
acementt
hera
pyinpost
me nopa
usa
lwome n.
A
DVE
RSEE
FFE
CTS ri
skofendomet
ri
alcancer(wheng
ive
nwi thoutprog
est
ero
ne ),
ble
edi
nginpos
tme nopaus
al
women,cle
arcel
ladenocar
cino
maofv a
ginai nf
ema l
esexposedt
oDESi nut
ero, ris
kof
t
hrombi
.Co nt
rai
ndic
a t
ions
—ER⊕ b reas
tc ance
r,hi
sto
ryo fDVTs,t
oba
ccouseinwome n>35
ye
arsol
d.
Sel
ect
ivees
trogenr
ecept
ormodul
ator
s
Cl
omi
phene Antag
onis
tates
trogenrece
p t
orsinhypot
hala
mus .Preve
ntsnormalfe
edbackinhi
bit
ionand

rel
eas
eofLHa ndFSH fromp it
uit
ary
,whichsti
mul a
tesovul
ati
on.Use
dt otre
atinfe
rti
li
ty
duetoanovul
ati
on(eg,PCOS) .SERMsma yc a
us ehotfashes
,ovar
iane
nlargement,multi
ple
si
multa
neouspregnanci
es,vi
sualdis
tur
bances
.
T
amox
ifen Antag
onista
tbr
eas
t;ag
onista
tbone,ut
erus
; ri
skoft
hromboe
mboli
cevent
s(e
spe
ciall
ywith
TamoxifIN goes IN the uterus.
smoking nde
)a ndometr
ialc
ancer
.Usedtotr
eata
ndpreve
ntr
ecur
renc
eofER/PR b
⊕ re
ast
You can RELAX with RELAXifene. cancer
.
Ral
oxi
fene Antag
onis
tatbr
eas
t,ute
rus;a
gonista
tbone
; r
is
koft
hro
mbo e
mbo l
icev
ent
s(e
spe
cial
lywi
th
smoking
)butnoi
nc r
ease
driskofendome
tri
alca
nce
r(vst
amoxi
fen)
;us
edpri
mari
lyt
otre
at
ost
eopor
osi
s.
Tamoxifen would be equally safe to use in a patient with a hysterectomy since they would not have an endometrium.
Ar
omat
asei
nhi
bit
ors Ana
str
ozo
le,l
etr
ozo
le,e
xeme
sta
ne.
mE
CHA
NIS
m I
nhi
bitpe
riphe
ralc
onv
ers
iono
fandr
oge
nst
oes
tr
oge
n.
C
lI
NI
CAlU
SE ER⊕ b
rea
stc
anc
eri
npos
tme
nopa
usa
lwo
men.
Hormoner
epl
acement Usedforrel
ie
forprev
enti
onofme nopaus
alsympt
oms(eg
,hotfashe
s,vagi
nalat
rophy)
,
ther
apy ost
eoporos
is(e s
tr
ogen, ost
eoclas
tact
ivi
ty
).
Unoppo s
edestr
ogenrepl
ace
me ntther
apy ris
kofend
ometr
ialc
ancer,prog
est
ero
ne/pr
oge
sti
nis
added.Pos
sibl
eincr
ease
dc a
rdiov
a s
cul
arri
sk.
6
ve R E
P ROD UC
TIVE
—P HARmAC
OlOgy
Pr
oges
tins Le
vono
rge
str
el,
medr
oxy
pro
ges
ter
one
,et
onog
est
rel
,no
ret
hindr
one
,me
ges
tr
ol.
C
mEHA
NIS
m Bi
ndpro
ges
ter
oner
ece
pto
rs,g
rowt
hand v
asc
ula
riz
ati
ono
fend
ome
tri
um,t
hic
kenc
erv
ica
l
muc
us.
C
lII
NClU
A S
E Cont
rac
epti
on(f
ormsincl
udepil
l,int
raut
eri
nedevi
ce,i
mplant,depoti
nject
ion)
,endometr
ial
c
ancer
,abnor
malute
r i
nebl
eeding.Prog
est
inchal
leng
e:pr
esenceofwi t
hdrawalbl
eedi
ng
e
xcl
udesanat
omicdefe
cts(
eg,Ashermansyndr
ome)andchronicanovula
ti
onwi t
houtes
trog
en.
Ant
ipr
oges
tins Mi
fe
pri
st
one
,ul
ipr
is
tal
.
C
mEHA
NIS
m Co
mpe
tit
iv
einhi
bit
orso
fpr
oge
sti
nsa
tpr
oge
ste
roner
ece
pto
rs.
C
lII
NClU
A S
E Te
rmi
nat
ionofpr
egna
ncy(
mif
epr
is
tonewi
thmi
sop
ros
tol
);e
mer
genc
ycont
rac
ept
ion(
uli
pri
st
al)
.
Combined Progest
insande t
hinylest
radiol;
formsincl
udepi l
l,patch,vaginalring .
cont
racept
ion Estroge
na ndprogesti
nsinhibitLH/FSHa ndthuspr ev e
nte s
trogens urge.Noes t
roge
ns ur
ge no
LHs ur g
e noo vul
ati
on.
Progest
inscausethicke
ningofc ervi
calmucus,therebylimiti
nga c
ce ssofspe
rmt outerus.
Progesti
nsals
oinhi bi
tendo metri
alpro
lif
era
tion end ometrium islesssui
tab
let ot
he
implantati
onofa nembr y
o.
Co ntr
aindic
ati
ons:smo ke
rs>3 5yearsol
d(r i
skofc ardiovas
cul a
rev ents
),pa
tientswi
th ri
skof
cardiovas
cula
rdi s
ease(i
ncludinghist
oryofvenoust hromboe mbo li
sm,c oronaryart
erydis
eas
e,
stro
ke),migra
ine(e s
pecia
llywithaura)
,breas
tc a
nc er,li
verdisease
.
Copperi
ntr
aut
eri
nedevi
ce
C
mEHA
NIS
m Pr
oduc
esl
oc ali
nfammat
oryr
eac
tio
nto
xict
ospe
rma
ndo
va,p
rev
ent
ingf
ert
il
iz
ati
ona
nd
i
mpla
nta
tion;hor
monef
ree.
C
lII
NClU
A S
E Long
-ac
tingr
eve
rsi
blec
ont
rac
ept
ion.
Mos
tef
fec
tiv
eeme
rge
ncyc
ont
rac
ept
ion.
A
DVE
RSEE
FFE
CTS Heav
ierorl
ongermens
es,dy
sme
nor
rhe
a.Ri
sko
fPI
D wi
thi
nse
rti
on(
cont
rai
ndi
cat
edi
nac
tiv
e
p
elvi
cinfe
cti
on).
T
ocol
yti
cs Medic
ati
onsthatr
elaxt
heuterus;incl
udet
erbut
ali
ne(β2-
agonis
tact
ion)
,nif
edi
pine(Ca 2
+c hanne
l
bl
ocker
),i
ndomethaci
n(NSAI D).Usedto contr
act
ionfr
equencyinpret
ermlaboranda ll
ow
t
imeforadminis
tr
ati
onofster
o i
ds(t
opromotefe
tall
ungma tur
ity
)ortr
ansf
ert
oa ppropria
te
medi
calcent
erwithobst
etr
icalcare
.
Danaz
ol
C
mEHA
NIS
m Sy
nthe
tica
ndr
oge
ntha
tac
tsa
spa
rti
ala
goni
sta
tandr
oge
nre
cept
ors
.
C
lII
NClU
A S
E End
ome
tri
osi
s,he
redi
tar
yang
ioe
dema
.
A
DVE
RSEE
FFE
CTS Wei
ghtgai
n,edema,ac
ne,hir
sut
is
m,ma
scul
ini
zat
ion, HDLl
eve
ls,
hepa
tot
oxi
cit
y,i
diopa
thi
c
i
ntr
acr
ania
lhyper
tens
ion.
UWORLD= A 24yo woman, G1P1, comes to the office for an annual visit. She is up to date with cervical cancer screening and HPV
vaccines. She is in a monogamous relationship with her husband and has negative chlamydia and gonorrhea screening. She has
been using a progestin-only pill since giving birth a year ago. She would like to switch to a combined oral contraceptive as she is no
longer breastfeeding. What is the primary mechanism of pregnancy prevention when she switches to a combined oral contraceptive?
Reduction of serum gonadotropin levels (21%) while 64% messed up and chose impairment of sperm penetration into the uterus.
Progestin is responsible for pregnancy prevention in all hormonal contracpetion. Estrogen is often included to improve the bleeding
profile. Combined hormonal contraceptives suppress GnRH in the hypothalamus, decreasing FSH and LH synthesis and inhibiting
ovulation. The progestin-only pill and levonorgestrel IUD prevent pregnancy by thickening the cervical mucus to prevent sperm entry.
RepRoduct ive R EPRODUCT
IVE
—PHAR mA
C Ogy S
Ol ecti oNi i
i 6
43
T
est
ost
erone,
met
hyl
tes
tos
ter
one
mE
CHA
NIS
m Ag
oni
st
sata
ndr
oge
nre
cep
tor
s.
C
lI
NI
CAlU
SE Tr
eathy
pogona
dismandp r
omotedev
elo
pme
ntof2
°se
xcha
rac
ter
is
ti
cs;s
ti
mul
at
eana
bol
is
mto
pr
omoter
ecove
ryaf
terburnori
njur
y.
A
DVE
RSEE
FFE
CTS Masculi
niz
ati
oninfe
males
;i nt
rat
est
icul
art
est
ost
eronei
nmalesbyinhibi
ti
ngre
lea
seofLH(v
ia
ne
ga t
iv
efeedba
ck) gonada
latr
ophy.Pr
ematur
ec l
osur
eofe
piphys
e a
lplat
es.
LDL, HDL.
Ant
iandr
ogens
F
inas
ter
ide α-
5 reductas
einhibi
tor(c onvers
ionof Te stos t
er o ne5α- r
e duc tase DHT( mo repot ent ).
t
est
oster
onetoDHT) .Us edforBPHa nd
male-
p a
tte
rnbaldness.Adv e
rseeff
ects
: Finasteride is the best answer for treating BPH, but if the patient is also hypertensive,
then choose tamsulosin. If the patient has BPH and pulmonary HTN, give tadalafil.
gy
ne comast
iaandsexua ldysfunct
ion.
F
lut
ami
de Nons
ter
oidalc
ompet
it
iveinhi
bit
orata
ndr
oge
n
r
ece
ptors.
Usedf
orpros
tatec
arci
noma.
Ket
ocona
zol
e I
nhibi
tss
ter
oidsynt
hesi
s(i
nhibi
ts1
7,2
0
de
smo l
ase
/17α-
hydro
xyla
se)
. UsedinPCOStor
educea
ndrog
e ni
csy
mptoms.
Spi
ronol
act
one I
nhibi
tss
ter
oidb
indi
ng,1
7,2
0de
smol
ase
/1α-
7 Bothcanc
aus
egynec
omast
iaandameno
rrhe
a.
hy
droxy
las
e.
Prazosin, Terazosin, Doxazosin, and Tamsulosin are all the alpha-1 selective alpha antagonists. However, Prazosin also helps with PTSD and the first 3 also help with hypertension.
T
ams
ulos
in α1-
ant
agoni
stus
edt
otr
eatBPH b
yinhi
bit
ings
moot
hmus
clec
ont
rac
tion.
Se
lec
tiv
efrα1A/
o Dre
cept
ors(
foundonp
ros
tat
e)v
sva
scul
arα1Br
ece
pto
rs.
Phosphodi
ester
ase Si
lde
nafil
,va
rde
nafil
,ta
dal
afil
.
type5inhi
bit
ors
mE
CHA
NIS
m I
nhibi
tPDE-5 cGMP pr
olonged Si
ldenafl
,va
rde
nafl
,andt
ada
laflfl
lthe
s
moo t
hmus cl
erela
xati
oninrespons
etoNO penis
.
bloodfowincorpuscav
ernosum ofpe
nis
,

pul
mo naryv
ascula
rresi
st
ance.
C
lI
NI
CAlU
SE Ere
cti
ledys
func ti
on,pul
mona
ryhy
per
tens
ion,
BPH (
tada
lafilonly
).
A
DVE
RSEE
FFE
CTS He a
dac
he,fus
hing,dys
pepsi
a,cyanopi
a Ho
“ tandsweat
y,
”butt
henHea
dac
he,
(bl
ue-
ti
ntedv
isi
on).Ri
skofli
fe-
threa
teni
ng He
art n,Hy
bur pot
ens
ion.
hypot
ens
ioni
npa ti
ent
staki
ngnitrat
es.
Arteriolar vasodilator similar to hydralazine, so it shares the reflex sympathetic activation which results in tachycardia, and stimulates RAAS which results
Mi
noxi
dilin edema due to sodium and water retention. Add sympatholytics and diuretics to counteract such compensatory mechanisms. Currently sold as Rogaine.
mE
CHA
NIS
m Di
rec
tar
ter
iol
arv
aso
dil
at
or.
C
lI
NI
CAlU
SE Andr
oge
net
ica
lope
cia(
pat
ter
nba
ldne
ss)
,se
ver
ere
fra
ctor
yhy
per
tens
ion.
6
ve

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Repro Annotated First Aid 2019

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Prepared for students. Amir Mullick -- YouTube.com/USMLELive Best of luck.

A 4yo boy is being evaluated for failure to thrive, SOB, and 4

Also called pharyngeal groove.

Top two images -

Bottom two photos -

Mesonephric does not have "para" because Ov

Mullerian agenesis also has a blind d

UWORLD= A 25yo woman g4, p0, comes to the

UWORLD= A 28yo woman, g1p0, goes into labor at 38 weeks

FSH --> Sertoli cells --> Inhibin B --> (-) FSH

In males, we end up with 4 sperm cells.

Being 2 is better than being alone.

Normal proliferative endometrium consists of uniform, nonbranching,

nonbudding glands evenly distributed throughout a uniform stroma.

Ovulation is at the late-proliferative phase, which has coiled glands and

acidsforut ilizationb ythef etus .

In 1' hypogonadism, there will be LH but the

Andr ogeni ns ens it ivi t y De f

<-- High magnification micrograph of a Brenner tumor

D- Dysgerminoma= "Fried egg" cells. hCG/LDH.

A- Mucinous cystadenocarcinoma would not have endometrial hyperplasia because it

A B C Fibroadenoma from a UWORLD question.

A -- DCIS (Black; neoplastic cells in duct) (Blue; engorged blood vessel)

High magnification view of seminoma, which is composed of clear cells.

This is a classic presentation of uterine fibroids and the patient has

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