fatty degeneration, autolysis, removal by macrophages and gradual 24–36 hours after ovulation (which occurs approximately 14 days
replacement with fibrous tissue. Eventually, after 2 months, a small, before the next menstrual flow). In the early secretory phase, glycogen
whitish, scar-like corpus albicans is all that remains. masses accumulate in the basal cytoplasm of the epithelial cells lining
If fertilization does occur, implantation of the blastocyst into the the glands, where they are often associated with lipid. Giant mitochon-
uterine endometrium usually begins 7 days later and the embryonic dria appear and are associated with semi-rough endoplasmic reticulum.
trophoblast then starts to produce hCG. The chorionic gonadotrophin There is an obvious increased polarization of the gland cells: nuclei are
stimulates the corpus luteum of menstruation to grow, and it becomes displaced towards the centre of the cells, and Golgi apparatus and secre-
a corpus luteum of pregnancy. It normally increases in size from 10 mm tory vesicles accumulate in the supranuclear cytoplasm. The nuclear
in diameter to 25 mm at 8 weeks of gestation and can be seen clearly channel system is prominent and nuclei enlarge. Nascent secretory
on ultrasound. It secretes progesterone, oestrogen and relaxin, and func- products may be detected immunohistochemically within the cells.
tions throughout pregnancy, although it gradually regresses as its endo- Progestational effects on the stroma (known as the decidual reaction)
crine functions are largely replaced by the placenta after 8 weeks’ are also evident in the early secretory phase. Nuclear enlargement occurs
gestation. Its diameter is reduced by the end of pregnancy to 1 cm. In and the packing density of the resident stromal cells increases, due, in
the next few months, it degenerates, like the corpus luteum of men- part, to the increase in volume of gland lumina and onset of secretory
struation, to form a corpus albicans. activity in the epithelial compartment.
By the mid-secretory phase, the endometrium may be up to 6 mm
Ovarian medulla
deep. The basal epithelial glycogen mass is progressively transferred to


The medulla is highly vascular. It contains numerous veins and spiral the apical cytoplasm, and nuclei return to the cell bases. The Golgi
arteries that enter the hilum from the mesovarium and lie within a loose apparatus becomes dilated and products, including glycogen, mucin
connective tissue stroma. Small numbers of cells (hilus cells) with and other glycoproteins, are released from the glandular epithelium
characteristics similar to interstitial (Leydig) cells in the testis are found into the lumen by a combination of apocrine and exocrine mecha-
in the medulla at the hilum; they may be a source of androgens. nisms; this activity reaches a maximum 6 days after ovulation. These
secretory changes are considerably less pronounced in the basal gland
Menopause
cells and the luminal epithelium than in the glandular cell population
At the menopause, ovulation ceases and various microscopic changes
of the stratum functionalis. There is a notable stromal oedema and a
ensue within the ovarian tissues. The stroma becomes denser, the tunica
corresponding decrease in the density of collagen fibrils. At the same
albuginea thickens and the ovarian surface epithelium thins. However,
time, the endoplasmic reticulum and Golgi apparatus become more
many follicles persist within the cortex.
prominent; there is evidence for collagen synthesis and degradation,
presumably reflecting ongoing matrix remodelling.
In the late secretory phase, glandular secretory activity declines.
MENSTRUAL CYCLE
Decidual differentiation occurs in the superficial stromal cells that sur-
round blood vessels; this transformation includes nuclear rounding and
The onset of menstruation (menarche) occurs between the tenth and an increased cytoplasmic volume, reflecting an increase in and dilation
seventeenth years of life, with a peak between 12 and 14 years. The of the rough endoplasmic reticulum and Golgi systems, and cytoplas-
uterus, ovaries and vagina undergo changes during the menstrual cycle, mic accumulation of lipid droplets and glycogen. The cells begin to
which normally lasts approximately 28 days. A follicle begins a period produce basal lamina components, including laminin and type IV
of development in the ovary during the first days of the cycle, and collagen.


matures and ruptures mid-cycle (approximately day 14 of a 28-day Ultrasound is frequently used in the clinical evaluation of the
cycle) to release a secondary oocyte. The wall of the follicle is then endometrium. In the early secretory phase, the endometrium is identi-
transformed into the corpus luteum, which secretes progesterone (luteal fied as a thin echogenic line, a consequence of specular reflection from
phase). About 10 days after ovulation, the corpus luteum begins to the interface between opposing surfaces of endometrium. During the
regress, then ceases to function and is replaced by fibrous tissue. The late proliferative phase, the endometrium appears as a triple layer: a
breakdown of the endometrium that follows this cessation of function central echogenic line (due to the apposed endometrial surfaces), sur-
is due to the reducing levels of progesterone and oestrogen as the corpus rounded by a thicker hypoechoic functional layer, and bounded by an
luteum degenerates. outer echogenic basal layer. During the secretory phase, the functional
The changes that occur in the endometrium during the menstrual layer surrounding the echogenic line becomes more hyperechoic as a
cycle may be divided into three phases: proliferative, secretory and result of the increased mucus and glycogen within the glands and the
menstrual (Fig. 77.37). increased number of interfaces caused by the development of tortuous
spiral arteries (Fig. 77.38).
PROLIFERATIVE PHASE
MENSTRUAL PHASE
In the early proliferative phase, even before the menstrual flow ceases,
the epithelium from the persisting basal parts of the uterine glands Prior to menstruation, three layers can be recognized in the endometrium:
grows over the surface of the endometrium, which has been denuded the strata compactum, spongiosum and basale. In the stratum compac-
by menstruation. Re-epithelialization is complete 5–6 days after the tum, which is next to the free surface, the necks of the glands are only
start of menstruation. Initially, the tissue is only 1–2 mm thick and is slightly expanded and the stromal cells show a distinct decidual reac-


lined by low cuboidal epithelium. The glands are straight and narrow, tion. In the stratum spongiosum, the uterine glands are tortuous,
and their lining cells are short columnar. The apical cell surface contains dilated and, ultimately, only separated from one another by a small
microvilli; some cells are ciliated. The stroma is dense and contains amount of interglandular tissue. The stratum basalis, next to the uterine
small numbers of lymphocytes. During days 10–12 of the proliferative muscle, is thin and contains the tips of the uterine glands embedded
phase, the endometrium thickens. Cells divide in response to rising in an unaltered stroma.


menstrual cycle
1307
77
RETPAHC
Ovary
Primordial follicles Developing follicles Ovulation Corpus luteum Corpus albicans
Endometrium
2 4 6 8 10 12 14 16 18 20 22 24 26 28
Menstrual Proliferative Early secretory Mid-secretory Late secretory
(days 1–3) (days 4–13) (days 14–18) (days 19–23) (days 24–28)
Fig. 77.37 Stages in the menstrual cycle with concomitant changes in the endometrium. Note that developing antral follicles are selected from cohorts
of follicles recruited in earlier cycles. The ten lower panels are histological sections of endometrium at the cycle times indicated (low magnification on top
and high magnification below in each case).
endometrium often diminishes in thickness. Blood escapes from the
superficial vessels of the endometrium, forming small haematomata
beneath the surface epithelium (see below). The stratum functionalis,
next to the free surface, is shed piecemeal, leaving mainly the stratum
basalis, adjacent to the uterine muscle; 65–75% of the thickness of the
endometrium may be shed. Blood and necrotic endometrium then
begin to appear in the uterine lumen, to be discharged from the uterus
through the vagina as the menstrual flow, which usually lasts 3–6 days.
The amount of tissue lost is variable, but usually the stratum compac-
tum and most of the spongiosum are desquamated.
VASCULAR CHANGES WITHIN THE UTERUS DURING
THE MENSTRUAL CYCLE
The vascular bed of the endometrium undergoes significant changes
during the menstrual cycle. The arteries to the endometrium arise from
a myometrial plexus and consist of short, straight vessels to the basal
portion of the endometrium, and more muscular spiral arteries to its
Fig. 77.38 Transvaginal ultrasound of the uterus, showing the triple-
superficial two-thirds. The venous drainage, consisting of narrow per-
layered endometrium. The central echogenic line is produced by the
pendicular vessels that anastomose by cross-branches, is common to


interface of the opposing surfaces of the endometrium. The functional
both the superficial and the basal layers of the endometrium. The capil-
layer of the endometrium surrounding the echogenic line is hypoechoic on
lary bed consists of an endothelium with a basal lamina that is discon-
the left, in keeping with late proliferative phase, but is becoming more
tinuous in the proliferative phase, but becomes more distinct by the
hyperechoic on the right, indicating the early secretory phase.
mid-secretory phase. Pericytes are present, some of which resemble
smooth muscle cells, and these are sometimes enclosed within the basal
The two upper strata are often grouped together as the functional lamina. The pericytes make contact with the endothelial cells by means
layer, stratum functionalis, of the endometrium; the lower (basal) layer of cytoplasmic extensions that project through the basal lamina.
is called the stratum basalis. As regression of the corpus luteum occurs, Enlargement of the pericytes starts in the early secretory phase, and
those parts of the stroma showing a decidual reaction, together with leads to a conspicuous cuff of cells in the mid- and late secretory phases.
the glandular epithelium, undergo degenerative changes and the The arterial supply to the basal part of the endometrium remains


FEmALE REPRoduCTivE sysTEm
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NoiTCEs
unchanged during the menstrual cycle. However, the spiral arteries to However, a number of growth factors, e.g. insulin-like growth factor-1
the superficial strata lengthen disproportionately. They become increas- (IGF-1), have been identified, which interact with oestrogen in promot-
ingly coiled and their tips approach the uterine epithelium more closely. ing uterine growth. The myometrium thins with advancing gestation
This leads to a slowing of the circulation in the superficial strata with from 2–3 cm thick in early pregnancy to 1–2 cm at term.
some vasodilation. Immediately before the menstrual flow, these vessels The upper third of the cervix (isthmus) is gradually taken up into
begin to constrict intermittently, causing stasis of the blood and anaemia the uterine body during the second month to form the ‘lower segment’
of the superficial strata. During the periods of relaxation of the vessels, (Fig. 77.40). The isthmus hypertrophies like the uterine body during
blood escapes from the devitalized capillaries and veins, causing the the first trimester and triples in length to about 3 cm. From the second
menstrual blood loss. The breakdown of the endometrium is a conse- trimester, the wall of the isthmus and that of the body are the same
quence of the reducing levels of progesterone and oestrogen as the thickness and their junction is no longer visible externally. This condi-
corpus luteum degenerates. tion persists until the middle of the third trimester, when the lower
uterine segment thins considerably to less than 1 cm in thickness. The
thicker myometrium above this transition is the main contractile
PREGNANCY AND PARTURITION
portion of the uterus that will generate the expulsive forces during
labour; the thin lower uterine segment, which begins just below the
During pregnancy, many morphological changes occur in the female vesico-uterine pouch and is thought to correspond to the level of the
reproductive system and associated abdominal structures. The uterus anatomical internal os, is more compliant and allows for the descent
enlarges to accommodate the developing fetus and placenta, and of the fetus in late pregnancy and during labour. As the lower uterine


various alterations take place in the pelvic walls, floor and contents that segment is thinner and less vascular than the upper uterus, it is the
allow for this expansion, and which anticipate parturition. At the end preferred site of incision during a caesarean section. In addition,
of gestation, dramatic changes occur that facilitate the passage of the because it is less contractile, there is a lower risk of uterine rupture in
baby through the birth canal and, subsequently, allow the pelvic organs subsequent pregnancies, compared with an incision made in the body
to return to the non-pregnant state (involution). of the uterus during a ‘classic’ caesarean section.
On average, human gestation is approximately 280 days (or The growing uterus generally emerges from the pelvis by the twelfth
40 weeks) from the date of the last menstrual period (LMP) (Ch. 14). week of pregnancy and can be palpated on the maternal abdomen just
However, as the menstrual history can often be inaccurate due to cycle above the pubic symphysis. By the twentieth week of pregnancy, the
irregularity or inaccurate recollection, an accurate gestational age can uterine fundus is at the level of the umbilicus and reaches the xiphister-
be calculated by ultrasound measurement of the fetal crown–rump num by 36 weeks. After 24 weeks of gestation, the distance between the
length in the first trimester (Fig. 77.39). A discrepancy of more than pubic symphysis and the uterine fundus generally corresponds to the
5–7 days from the LMP-estimated age is usually cause to revise the number of gestational weeks and is often used in clinical care as a
estimated date of confinement. For women presenting after the first screening method to detect a pregnancy that is measuring suspiciously
trimester, gestational dating can be based on other sonographically larger or smaller than expected. If there is more than a 2 cm discrepancy,
obtained fetal biometric measurements, such as the fetal biparietal a more accurate, sonographic assessment of fetal size and amniotic fluid
diameter, head circumference and femur length, although precision volume is indicated.
gradually decreases later in pregnancy (see Fig. 14.4). The increased
accuracy of gestational dating using sonographic fetal biometry rather Cervix and pregnancy
than menstrual history alone has significantly reduced the number of


pregnancies requiring induction of labour for post-term women.
During pregnancy, the uterine cervix is a relatively rigid, fibromuscular
structure that retains the developing fetus within the uterus. The rigidity
UTERUS IN PREGNANCY of the cervix appears to be related to the orientation of its collagen fibres
within a regular connective tissue matrix. The cervix gradually softens
and shortens in the weeks preceding labour. During active labour,
The function of the uterus in pregnancy is to retain the developing fetus
the cervix dilates to allow the fetus to descend through the birth canal.
and to provide a protected environment until a stage at which the fetus
The exact processes that allow softening, effacement and dilation of the
is capable of surviving ex utero. The uterus must grow, facilitate delivery
cervix are unclear, but are believed to include remodelling of the con-
of the fetus and then involute.
nective tissue matrix, probably mediated by an increase in the activity
The uterus grows dramatically during pregnancy, increasing in
of enzymes such as matrix metalloproteinase 1, a reduction in collagen
weight from about 50 g at the beginning of pregnancy to up to 1 kg at
concentration, a significant increase in the water content in the cervix,
term. Most of the weight gain is the result of increased vascularity and
an infiltration of macrophages and neutrophils, and an increased level
fluid retention in the myometrium. The increased growth of the uterine
of apoptosis.
wall is driven by a combination of mechanical stretching and endocrine
Transvaginal ultrasound examination allows for a robust evaluation
input. The mechanical load that increasing gestation imposes on the
of the cervix during pregnancy. Cervical length, dilation of the internal
uterine wall induces hypertrophy of uterine smooth muscle cells and is
os and bulging of the membranes into the canal can all be assessed
the major stimulus that increases smooth muscle mass. Some hyperpla-
(Fig. 77.41). Detection of a shortened cervical length in mid-gestation
sia occurs early on in pregnancy, mainly from the growth of the media
using transvaginal ultrasound is a strong risk factor for premature deliv-
of the myometrial arteries and veins. The myometrium is relatively
ery and has been used clinically to identify women at high risk of
unresponsive to additional endocrine stimulation during most of preg-


preterm delivery in order to plan appropriate management (Fonseca
nancy, a relative quiescence that is, in part, attributed to progesterone.
et al 2007, Hassan et al 2011, Owen et al 2009). Emerging sonographic
and MRI technologies are being used to investigate both the biome-
chanical properties and the microstructure of the cervix in pregnancy
and promise to shed light on the poorly understood mechanisms
involved in both normal and pathological cervical shortening in human
pregnancy (Feltovich et al 2012, House et al 2013).
Relations of the uterus in pregnancy
With uterine expansion, the ovaries and uterine tubes are displaced
upwards and laterally. The round ligaments become hypertrophied and
their course from the cornual regions of the uterus down to the internal
inguinal ring becomes more vertical. The broad ligament tends to open
out to accommodate the massive increase in the sizes of the uterine and
ovarian vessels. The uterine veins, in particular, can reach about 1 cm
in diameter and they appear to act as a significant reservoir for blood
during uterine contractions. Lymphatics and nerves expand their terri-
tories (the significance of this increased innervation is not clear because
paraplegic women are able to labour normally, albeit painlessly). Later
Fig. 77.39 Transabdominal ultrasound at 12 weeks, showing in pregnancy, the increase in intra-abdominal pressure produced by the
measurement of the crown–rump length to calculate the gestational age. gravid uterus may produce eversion of the umbilicus. On the skin over


Pregnancy and parturition
1309
77
RETPAHC
Body
Isthmus
Cervix
Anatomical internal os
Histological internal os
External os
Non-gravid First trimester First trimester (late)
Anatomical internal os
Histological internal os
External os
Second trimester Third trimester
Fig. 77.40 A frontal view of the uterus, showing the location and extent of the body, isthmus and cervix in the non-gravid and gravid uterus at different
stages in gestation. The isthmus forms the lower uterine segment with advancing gestation.
Fetal head Internal os External os
A
Endocervical canal
Fetal head Internal os
C
B Fig. 77.41 Transvaginal ultrasound at 36 weeks. A, Measurement of cervical length.
B, Posterior placenta praevia 18.5 mm from the internal os. C, A placenta completely
Lower border of placenta covering the internal cervical os, consistent with a complete placenta praevia.


FEmALE REPRoduCTivE sysTEm
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NoiTCEs
the abdomen, a combination of stretching and hormonal changes may Twin 1 Lumbar spine
produce stretch marks (striae gravidarum). In multiparous patients,
diastasis (diverification) of right and left rectus abdominis may occur
to accommodate the enlarging uterine fundus further. In the supine
position, the gravid uterus can cause aortocaval compression, leading
to reduced venous return to the heart and decreased cardiac output. In
some women, this can lead to symptomatic hypotension and symptoms
of nausea and faintness. These symptoms are minimized if the woman
lies on her left side, thereby deviating the gravid uterus and reducing
compression of the inferior vena cava.
The jejunum, ileum and transverse colon tend to be displaced
upwards by the enlarging uterus, whereas the caecum and appendix are
displaced to the right, and the sigmoid colon posteriorly and to the left.
Upward and lateral displacement of the appendix in later pregnancy
can cause difficulties in the diagnosis of appendicitis. The ureters are
pushed laterally by the enlarging uterus and, in late pregnancy, can be
compressed at the level of the pelvic brim, resulting in hydronephrosis
and loin pain. However, mild ureteric dilation is normal in pregnancy,
and is caused by progesterone-induced relaxation of smooth muscle in
the ureteric walls. The axis of the uterus is often dextrorotated by the
presence of the sigmoid colon; this rotation must be considered when
performing a hysterotomy at the time of caesarean section to avoid
injuring the large uterine vessels located bilaterally.
PELVIC CHANGES IN PREGNANCY
The presence of a pregnant uterus results in a change in the centre of
gravity of the body, especially in late pregnancy. In order to compensate
for this, the mother tends to straighten her cervical and thoracic spine,
and throw her shoulders back, resulting in a compensatory lumbar
lordosis. There is also a softening of the pubic symphysis and sacroiliac Twin 2 Bladder
joints, caused by production of relaxin and other pregnancy hormones,
Placenta praevia – low-lying placenta


leading to mild pelvic instability that may result in a waddling gait. covering internal cervical os
Softening also produces an increase in pelvic diameter, which is of
Fig. 77.42 A sagittal T2-weighted scan of a twin pregnancy with a
benefit during the time of labour. Significant joint relaxation may lead
placenta praevia overlying the internal cervical os.
to pubic symphysis diastasis, which, in severe cases, may produce debili-
tating pain during walking.
Advances in three-dimensional ultrasound imaging permit the real-
time visualization of the anatomical relationships and adaptations of
the pelvic floor in pregnancy. They also enable detection of pelvic floor
injury that might lead to symptomatic postpartum pelvic floor prolapse
(Dietz and Lanzarone 2005, Shek et al 2012).
PLACENTAL DEVELOPMENT
Placental attachment to the uterus occurs at the point where the blasto-
cyst becomes embedded, and is determined by a multitude of molecular
signalling pathways. In early pregnancy, the placental disc occupies a
large proportion of the uterine cavity and will often appear to be situ-
ated near the internal os. In the majority of cases, growth and stretching
of the uterus will usually draw the placenta upwards, away from the
cervix, by the end of pregnancy.
In about 1% of pregnancies, the position of the placenta will remain
over, or in close proximity to, the internal cervical os at the end of
pregnancy (see Fig. 77.41B; Fig. 77.42). This condition is called pla-
centa praevia and can be associated with vaginal bleeding during preg-
nancy and labour. If the placenta covers the internal os, or the lower
edge is less than 1–2 cm from the internal os, delivery by caesarean
section is generally indicated.
Normal trophoblastic development includes the remodelling of
Fig. 77.43 Doppler examination of the maternal and fetal circulation in
maternal spiral arterioles to allow for low-resistance flow into the inter-
pregnancy. A pulsed Doppler showing normal waveforms in the umbilical
villous space. Thus, the uteroplacental vasculature is a low-resistance, arteries at 28 weeks.
high-capacitance system. Antenatal ultrasound Doppler velocimetry can


be used during pregnancy to evaluate the resistance to flow in both the
uterine and the umbilical arteries, and may be helpful in the manage-
ment of high-risk pregnancies (Fig. 77.43). LABOUR
Abnormally invasive placentation can occur when trophoblastic
tissue invades through the decidua basalis and reaches the myometrium; The onset of labour is defined as the combination of regular uterine
this can lead to a morbidly adherent placenta and significant maternal contractions that are of sufficient intensity to produce progressive
morbidity. This condition, placenta accreta, occurs in approximately 3 effacement and dilation of the cervix. The process of labour is described
per 1000 births. When the trophoblastic tissue invades the myometrium, in three main stages.
it is referred to as placenta increta; if the placental tissue reaches the
uterine serosa, it is called a placenta percreta. In extreme cases, a pla- First stage
centa percreta can also invade into the maternal bladder mucosa. These The first stage of labour is the period during which the cervix progres-
conditions often require a hysterectomy. Prior uterine surgery, especially sively dilates until the fetus is able to descend into the birth canal and
multiple prior caesarean sections, is the most significant risk factor there is no longer any cervix palpable on vaginal examination. There is
(Fig. 77.44). little change in the uterine volume because myometrial contractions are


Pregnancy and parturition
1311
77
RETPAHC
Fig. 77.44 A gross photograph taken at the time of caesarean section in
a patient with a placenta accreta. Note the hypervascularity caused by
Fig. 77.45 The fetal surface of a recently delivered placenta. The spiral
the placental tissue invading into, and almost through, the myometrial
umbilical vessels in the umbilical cord and their radiating branches are
layer of the lower uterine segment, which is still covered with its serosal
seen through the transparent amnion. The maternal surface is exposed in
layer.
the lower and right corner of the figure. Note the fringes of amnion and
chorion, the majority of which have been cut away near the placental
margin.
isometric, and so there is minimal shortening of the muscle fibres.
Progress is determined by the equilibrium between forces generated by
myometrial contractions, especially from the fundus, and the resistance
(range 10–40 mm), and a surface area of approximately 30,000 mm2.
of the cervix.
It is thickest at its centre (the original embryonic pole), and rapidly
thins towards its periphery, where it continues as the chorion laeve.
second stage
The size of the placenta correlates well with the birth weight of the
The second stage of labour begins once the cervix is fully dilated, and
neonate.
ends with the delivery of the fetus. Cervical resistance is lost and myo-
Macroscopically, the fetal or inner surface, covered by amnion, is
metrial activity results in isometric contractions that aid descent of the
smooth, shiny and transparent, so that the mottled appearance of the
fetus in the birth canal. The head of the fetus usually enters the pelvis
subjacent chorion, to which it is closely applied, can be seen. The
with the occiput facing laterally. As the head descends further, the
umbilical cord is usually attached near the centre of the fetal surface,
occiput contacts the gutter-shaped pelvic floor formed by levator ani
and branches of the umbilical vessels radiate out under the amnion
and this promotes flexion and rotation of the occiput to the anterior
from this point; the veins are deeper and larger than the arteries. The


position. With further descent, the occiput escapes under the pubic
maternal surface of the placenta is finely granular and mapped into
symphysis and the head is born by extension. At this point, the head
some 15–30 lobes by a series of fissures or grooves. The placental lobes,
of the fetus regains its normal relationship with its shoulders, and slight
which are often somewhat loosely termed cotyledons, correspond, in
rotation (or restitution) of the head is seen. Further external rotation
large measure, to the major branches of the umbilical vessels. The
occurs as the leading shoulder is directed medially by the maternal
grooves correspond to the bases of incomplete placental septa, which
pelvic floor. The body of the fetus is now born by lateral flexion as one
become increasingly prominent from the third month onwards. They
shoulder slips underneath the symphysis and the posterior shoulder is
extend from the maternal aspect of the intervillous space (the basal
drawn over the frenulum.
plate) towards the chorionic plate (see Fig. 9.5) but do not quite reach
it. The septa are complex structures composed of components of the
Third stage
cytotrophoblastic shell and residual syncytium, together with mater-
The third stage of labour is the time from delivery of the fetus until nally derived material, including decidual cells, occasional blood vessels
delivery of the placenta. Prior to separation of the placenta, a large and gland remnants, collagenous and fibrinoid extracellular matrix,
proportion of the mother’s cardiac output passes through the uterine and, in the later months of pregnancy, foci of degeneration.
circulation. After separation in the third stage of labour, maternal exsan- In multiple pregnancies, the number of placentas is determined by
guination is only prevented by marked uterine contraction; the criss- the zygosity; for example, in twin gestations, dizygotic pregnancies will
crossing myometrial fibres act as a tourniquet, restricting blood flow to always have two placentas (dichorionic). Monozygotic pregnancies
the area that was the placental site. This process is usually expedited usually have a single placenta (monochorionic), but about one-third


clinically by the administration of oxytocic drugs in an attempt to limit will have two placentas; the number is determined by the timing of
maternal blood loss. Any condition that predisposes to poor uterine splitting of the embryonic mass (see Ch. 8 and Fig. 8.9). If the split
contraction, such as retained placental tissue, will increase the likeli- occurs within 3 days of fertilization, each fetus will have its own pla-
hood of postpartum haemorrhage. centa and amniotic sac (dichorionic diamniotic); splitting after the
third day following fertilization results in a monochorionic diamniotic
Placenta after delivery pregnancy (two amniotic sacs) and vascular communication within the
two placental circulations (Fig. 77.46); splitting after the ninth day
results in a single placenta and single amniotic sac (monochorionic
Separation of the placenta from the uterine wall takes place along the
monoamniotic); and splitting after the twelfth day results in conjoined
plane of the stratum spongiosum and extends beyond the placental
twins.
area, detaching the villous placenta, with associated fibrinoid matrix
and small amounts of decidua basalis; the chorio-amnion, together
Placental variations
with a superficial layer of the fused decidua capsularis; and the decidua
parietalis. When the placenta and membranes have been expelled, a
thin layer of stratum spongiosum is left lining the uterus; it soon The umbilical cord is usually attached near the centre of the placenta,
degenerates and is cast off in the early part of the puerperium. A new although it can occasionally insert more laterally and closer to the
epithelial lining is regenerated from the remaining stratum basalis. The placental margin; this condition is known as a battledore placenta
expelled placenta is a flattened discoid mass with an approximately (Fig. 77.47). Occasionally, the cord fails to reach the placenta itself and
circular or oval outline (Fig. 77.45). It has an average volume of ends in the membranes as a velamentous insertion. When insertion of


500 ml (range 200–950 ml), a weight of 470 g (range 200–800 g), a the cord is velamentous, the larger branches of the umbilical vessels
diameter of 185 mm (range 150–200 mm), a thickness of 23 mm traverse the membranes before they reach and ramify on the placenta


FEmALE REPRoduCTivE sysTEm
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NoiTCEs
(Fig. 77.48). They travel unprotected through the membranes to the
placenta, and this puts the fetus at risk because compression or tearing
of the vessels can disrupt blood flow to and from the fetus. This can be
particularly problematic when the vessels present themselves across the
cervical os, a condition called vaso praevia. An accessory (succenturiate)
placental lobe is occasionally present, connected to the main organ by
membranes and blood vessels. If it is inadvertently retained in utero after
delivery of the main placental mass, it can cause postpartum haemor-
rhage or infection. Other variations include placenta membranacea, in
which villous stems and their branches persist over the whole chorion;
and placenta circumvallata, where the placental margin is undercut by
a deep groove caused by an abnormally central insertion of the mem-
branes (Fig. 77.49).
Bonus e-book tables
Fig. 77.46 A vascular cast from a monochorionic diamniotic Table 77.1 Lymphatic drainage of the female genitalia.
twin pregnancy, showing vascular communications between both
placentas. (Courtesy of Dr Ling Wee, University College London Table 77.2 Innervation of the female genitalia.
Hospital.)
Insertion of umbilical cord into
chorio-amniotic menbrane
Insertion of umbilical
Chorionic plate
cord into placenta
Unprotected fetal
Umbilical cord vessels
Fig. 77.47 A battledore placenta showing the marginal insertion of the Fig. 77.48 Velamentous insertion of the umbilical cord, showing the cord
umbilical cord into the placenta. (Courtesy of Dr Michael Ashworth, inserting into the chorioamniotic membranes rather than the placental
Consultant Histopathologist, Great Ormond Street Hospital for Children, disc. (Courtesy of Dr Michael Ashworth, Consultant Histopathologist,
London.) Great Ormond Street Hospital for Children, London.)
Disc margin with no Circumvallate insertion of Disc margin with no Layer of fibrin at Membrane
membrane attachment membranes membrane attachment site of attachment attachment
A B


Fig. 77.49 Placenta circumvallata. A, The fetal surface and a thick ring of membranes on the fetal surface of the placenta. B, A section through the
placenta, showing that the membranes insert central to the edge of the placental disc. (Courtesy of Dr Michael Ashworth, Consultant Histopathologist,
Great Ormond Street Hospital for Children, London.)


1313
77
RETPAHC
Key references
KEY REFERENCES
Corton MM 2012 Anatomy. In: Hoffman B, Schorge JO, Schaffer JI et al (eds) multicenter, randomized, double-blind, placebo-controlled trial. Ultra-
Williams Gynecology, 2nd ed. New York: McGraw Hill. sound Obstet Gynecol 38:18–31.
A chapter that provides a comprehensive review of pelvic organs, blood A landmark randomized, controlled clinical trial that demonstrates the
vessels, lymphatics and nerve supply and supports of the pelvic organs. utility of progesterone supplementation for reducing the risk of preterm birth
in singleton pregnancies with a shortened cervix.
Delancey JO 2011 Surgical anatomy of the female pelvis. In: Rock JA, Jones
HW (eds) Te Linde’s Operative Gynecology, 10th ed. Philadelphia: Minto C, Hollings N, Hall-Craggs M et al 2001 Magnetic resonance imaging
Lippincott, Williams & Wilkins. in the assessment of complex Müllerian anomalies. Br J Obstet Gynaecol
A chapter that provides a detailed review of the supports of the vagina and 108:791–7.
the pelvic organs. An article that provides a detailed discussion of the formation and MRI
appearance of congenital anomalies of the uterus and Fallopian tubes.
Dietz HP, Lanzarone V 2005 Levator trauma after vaginal delivery. Obstet
Gynecol 106:707–12. Motta PM, Nottola SA, Familiari G et al 2003 Morphodynamics of the
A landmark study that prospectively identified levator trauma after vaginal follicular-luteal complex during early ovarian development and repro-
delivery using non-invasive three-dimensional ultrasound. ductive life. Int Rev Cytol 223:177–288.
An account that reviews the morphological and functional aspects of the
Feltovich H, Hall TJ, Berghella V 2012 Beyond cervical length: emerging
ovarian follicle, corpus luteum and germ cells using light microscopy,
technologies for assessing the pregnant cervix. Am J Obstet Gynecol 207:
electron microscopy and numerous drawings.
345–54.
A review article that describes emerging imaging technologies for visualizing Shek KL, Kruger J, Dietz HP 2012 The effect of pregnancy on hiatal dimen-


structural and architectural changes in the cervix in normal and abnormal sions and urethral mobility: an observational study. Int Urogynecol J
pregnancies. 23:1561–7.
A study that demonstrates the anatomical changes that occur in the pelvic
Grant LA, Sala E, Griffin N 2010 Congenital and acquired conditions of the
floor at the urethral hiatus during pregnancy.
vulva and vagina on magnetic resonance imaging: a pictorial review.
Semin Ultrasound CT MR 31:347–62. Shoja MM, Sharma A, Mirzaya N et al 2013 Neuroanatomy of the female
An article that reviews the typical imaging characteristics on MRI of the abdominopelvic region: a review with application to pelvic pain syn-
normal vagina, as well as congenital and acquired conditions of the vulva dromes. Clin Anat 26:66–76.
and vagina. A detailed review of the somatic and autonomic nerve supply of the female
genital system and female pelvis.
Hassan SS, Romero R, Vidyadhari D et al 2011 Vaginal progesterone reduces
the rate of preterm birth in women with a sonographic short cervix: a


Female reproductive system
1313.e1
77
RETPAHC
REFERENCES
Altchek A, Wasserman B, Deligdisch L et al 2008 Prepubertal distal longitu- Hassan SS, Romero R, Vidyadhari D et al 2011 Vaginal progesterone reduces
dinal vaginal folds. J Pediatr Adolesc Gynecol 21:351–4. the rate of preterm birth in women with a sonographic short cervix: a
Anderson RA, McLaughlin M, Wallace WH et al 2014 The immature human multicenter, randomized, double-blind, placebo-controlled trial. Ultra-
ovary shows loss of abnormal follicles and increasing follicle develop- sound Obstet Gynecol 38:18–31.
mental competence through childhood and adolescence. Hum Reprod A landmark randomized, controlled clinical trial that demonstrates the
29:97–106. utility of progesterone supplementation for reducing the risk of preterm birth
in singleton pregnancies with a shortened cervix.
Attah AA, Hutson JM 1991 The anatomy of the female gubernaculum is
different from the male. Aust NZ J Surg 61:380–4. House M, McCabe R, Socrate S 2013 Using imaging-based, three-dimensional
Badouraki M, Christoforidis A, Economou I et al 2008 Sonographic assess- models of the cervix and uterus for studies of cervical changes during
ment of uterine and ovarian development in normal girls aged 1 to 12 pregnancy. Clin Anat 26:97–104.
years. J Clin Ultrasound 36:539–44. Kimberley N, Hutson JM, Southwell BR et al 2012 Vaginal agenesis, the
Bardo DM, Black M, Schenk K et al 2009 Location of the ovaries in girls hymen, and associated anomalies. J Pediatr Adolesc Gynecol 25:54–8.
from newborn to 18 years of age: reconsidering ovarian shielding. Lee JF, Maurer VM, Block GE 1973 Anatomic relations of pelvic autonomic
Pediatr Radiol 39:253–9. nerves to pelvic operations. Arch Surg 107:324–8.


Bill AH, Hall DG, Johnson RJ 1975 Position of rectal fistula in relation to Leung AK, Robson WL 1992 Labial fusion and urinary tract infection. Child
the hymen in 46 girls with imperforate anus. J Pediatr Surg 10:361–5. Nephrol Urol 12:62–4.
Chen C, Huang L, Liu P et al 2014 Neurovascular quantitative study of the Minto C, Hollings N, Hall-Craggs M et al 2001 Magnetic resonance imaging
uterosacral ligament related to nerve-sparing radical hysterectomy. Eur in the assessment of complex Müllerian anomalies. Br J Obstet Gynaecol
J Obstet Gynecol Reprod Biol 172:74–9. 108:791–7.
Corton MM 2012 Anatomy. In: Hoffman B, Schorge JO, Schaffer JI et al (eds) An article that provides a detailed discussion of the formation and MRI
Williams Gynecology, 2nd ed. New York: McGraw Hill. appearance of congenital anomalies of the uterus and Fallopian tubes.
A chapter that provides a comprehensive review of pelvic organs, blood Motta PM, Nottola SA, Familiari G et al 2003 Morphodynamics of the
vessels, lymphatics and nerve supply and supports of the pelvic organs. follicular-luteal complex during early ovarian development and repro-
Delancey JO 2011 Surgical anatomy of the female pelvis. In: Rock JA, Jones ductive life. Int Rev Cytol 223:177–288.
HW (eds) Te Linde’s Operative Gynecology, 10th ed. Philadelphia: Lip- An account that reviews the morphological and functional aspects of the
pincott, Williams & Wilkins. ovarian follicle, corpus luteum and germ cells using light microscopy,
A chapter that provides a detailed review of the supports of the vagina and electron microscopy and numerous drawings.
the pelvic organs. Owen J, Hankins G, Iams JD et al 2009 Multicenter randomized trial of
Dietz HP, Lanzarone V 2005 Levator trauma after vaginal delivery. Obstet cerclage for preterm birth prevention in high-risk women with short-
Gynecol 106:707–12. ened midtrimester cervical length. Am J Obstet Gynecol 201:375.


A landmark study that prospectively identified levator trauma after vaginal Salardi S, Orsini LF, Cacciari E et al 1985 Pelvic ultrasonography in pre-
delivery using non-invasive three-dimensional ultrasound. menarcheal girls: relation to puberty and sex hormone concentrations.
Arch Dis Child 60:120–5.
Feltovich H, Hall TJ, Berghella V 2012 Beyond cervical length: emerging
technologies for assessing the pregnant cervix. Am J Obstet Gynecol Sforza C, Ferrario VF, De Pol A et al 1993 Morphometric study of the human
207:345–54. ovary during compartmentalization. Anat Rec 236:626–34.
A review article that describes emerging imaging technologies for visualizing Shek KL, Kruger J, Dietz HP 2012 The effect of pregnancy on hiatal dimen-
structural and architectural changes in the cervix in normal and abnormal sions and urethral mobility: an observational study. Int Urogynecol J
pregnancies. 23:1561–7.
A study that demonstrates the anatomical changes that occur in the pelvic
Fonseca EB, Celik E, Parra M et al 2007 Fetal Medicine Foundation Second
floor at the urethral hiatus during pregnancy.
Trimester Screening Group. Progesterone and the risk of preterm birth
among women with a short cervix. N Engl J Med 357:462–9. Shoja MM, Sharma A, Mirzaya N et al 2013 Neuroanatomy of the female
Grant LA, Sala E, Griffin N 2010 Congenital and acquired conditions of the abdominopelvic region: a review with application to pelvic pain syn-
vulva and vagina on magnetic resonance imaging: a pictorial review. dromes. Clin Anat 26:66–76.
Semin Ultrasound CT MR 31:347–62. A detailed review of the somatic and autonomic nerve supply of the female
An article that reviews the typical imaging characteristics on MRI of the genital system and female pelvis.
normal vagina, as well as congenital and acquired conditions of the vulva Speroff L, Fritz M 2004 Clinical Gynecologic Endocrinology and Infertility.
and vagina. Philadelphia: Lippincott, Williams and Wilkins.


COMMENTARY
The neurovascular bundles of
8.1
the prostate
Robert P Myers
The neurovascular bundles are discrete anatomical structures flanking The pelvic plexus consists of sympathetic and parasympathetic com-
the posterolateral surfaces of the prostate. They contain autonomic ponents (Fig. 8.1.1). A major portion of the plexus consists of the
nerves that become cavernous nerves once they enter the corpora cav- inferior hypogastric plexus, where the sympathetic innervation is
ernosa and corpus spongiosum more distally. The neurovascular centred on the lateral surfaces of the rectum, superior and posterior to
bundles are so named because, where they course along the prostate, the seminal vesicles. Nerve roots comprising the parasympathetic
the bundles, which serve as a visual marker in radical prostatectomies, portion exit sacral foramina S2–4 and join and intermix with the
contain small arteries and veins, as well as nerves (Walsh et al 1983). hypogastric plexus. Both sympathetic and parasympathetic nerve fibres
They extend distally from the vascular pedicle at the vesicoprostatic entering the neurovascular bundles emerge from the pelvic plexus
junction and base of the prostate, and reach all the way to the prostatic to embrace both the lateral surfaces of the seminal vesicles and the
apex. Nerves in the neurovascular bundles are derived from the pelvic posterolateral surfaces of the prostate. Proximal to the vascular pedicle
plexus. to the prostate, the nerves course particularly close to the lateral surfaces
Fig. 8.1.1 Pelvic plexus origins with ramifications
distally into the prostatic and cavernous plexuses,
with autonomic nerves to seminal vesicles,
bladder and rectum. Variable configurations
include prostate shape with blunt apex to
accentuate the inward turn of the neurovascular
bundle towards the prostato-urethral junction, and
anterior 90° prostatic urethral angulation into the
vesical neck. Inset: radical prostatectomy
specimen. (Used with permission of Mayo
Foundation for Medical Education and Research.)
e72


The neurovascular bundles of the prostate
e73
1.8
YRATNEMMOC
of the seminal vesicles (Lunacek et al 2005, Schlegel and Walsh 1987), et al 2005). This point of decussation is in proximity to the triangular
and thus mobilization of the seminal vesicles during radical prostatec- tip of Denonvilliers’ fascia as it merges to join the posterior median
tomy is of potential risk to nerve integrity. On occasion, nerves run in raphe of the urethra. On the basis of anatomical study, passing a needle
a mass anterior to the seminal vesicles (van der Zypen 1988). As nerves posteriorly close to this junction of the neurovascular bundles (Rocco
from the pelvic plexus run distally, branches are given off to the bladder, stitch; Rocco et al 2007) must be done carefully because there is certain
ureters, seminal vesicles, vasa deferentia, levator ani, rectum, prostate risk of nerve entrapment. The basket configuration makes the intrafas-
and membranous urethra (Walsh et al 1983, Costello et al 2004, cial dissection and removal of the prostate the most nerve-preserving
Durward 1953, Arai 2006). Individual variation in the distribution of technique (Walz et al 2010).
pelvic plexus nerves relative to where they join the neurovascular In an anatomical study of transverse prostate sections, Kiyoshima
bundle is well recognized, and four distribution types have been identi- and colleagues (2004) found that, in approximately half of prostates,
fied by intraoperative nerve stimulation and measurement of concomi- the nerves were in the typical bundle configuration dominant at the 4
tant intracavernosal corporal body pressures (Takenaka et al 2011). and 5 o’clock and the 7 and 8 o’clock positions, as was originally
These four tentative nerve distribution types have not yet been corrobo- described. However, in the other half of the specimens, the nerves were
rated by gross dissection specimens. more evenly distributed on the posterolateral surfaces of the prostate.
Residual autonomic branches of the neurovascular bundles pass This finding has affected the conduct of nerve-sparing radical retropubic


beneath the pubic arch to innervate the corpora cavernosa and corpus prostatectomies calling for mobilization of the nerves with initial high
spongiosum as the cavernous nerves (Walsh et al 1983, Durward 1953, lateral prostate fascial incision and release (Montorsi et al 2005). This
Paick et al 1993, Alsaid et al 2011, Müller 1836). Nerves branch both manœuvre allows as many nerves as possible to be mobilized laterally
posteriorly, into the corpus spongiosum, and anterolaterally, to away from the prostate, even if the major nerves are still found at the
intermesh with the dorsal sensory nerves of the penis; the latter act as 4 and 5 o’clock positions, as based on stimulation study (Kaiho et al
a scaffold for both proximal and distal entry of cavernous nerve fibres 2009). While dominance of nerves is demonstrated rectolaterally, one-
into the cavernous bodies. fifth to one-fourth of nerves have been found along the ventral circum-
After radical prostatectomy with prostate removed, the preserved ference of the prostate (Eichelberg et al 2007).
neurovascular bundles sit prominently on the rectal surface and course As autonomic nerves pass the prostato-urethral junction with a
distally from the bladder to embrace either side of the protruding medial swing inwards, hugging the prostate apex at the prostato-
membranous urethra and external striated urethral sphincter (rhab- urethral junction, they approach very close to the rhabdosphincter and
dosphincter) (Fig. 8.1.2). membranous urethra; anterolateral fibres extend as far anteriorly as the
Within neurovascular bundles next to the prostate, the major nerves 10 and 2 o’clock positions en route to becoming true cavernous nerves
vary in their distance from the underlying prostatic fascia or capsule. If (Costello et al 2004, Lepor et al 1985). In radical retropubic prostatec-
they are close, they are more easily injured in the lateral dissection of tomies, exceptional care must be taken to secure and transect the


the neurovascular bundles during radical prostatectomy. If they run next dorsal vascular complex without trapping these anteriorly directed
to a bleeding vessel that needs to be secured, there is greater likelihood nerve fibres with suture material or transecting them with blunt dissec-
that an adjacent nerve may be injured in the process. Within the neu- tion manœuvres and instruments passed distal to the prostato-urethral
rovascular bundles, cross-sectional nerve diameters of 0.04–0.37 mm junction. An immunohistochemical study found 15% of sympathetic
have been measured with a cross-reference human hair 0.02 mm in and 6.8% of parasympathetic fibres disposed anterolaterally at the
diameter (Myers 2002a). The periprostatic fascia is multilayered, and prostate apex; the distribution distal to the apex was not detailed (Cos-
compartmentalizes the neurovascular bundles on cross-section; pro- tello et al 2011). Beyond the prostatic plexus, a cavernous plexus has
erectile nerves are situated more posteriorly (Costello et al 2004). been described that is mixed within the anterior rhabdosphincter,
With the posterior Denonvilliers’ fascia removed, cadaveric dissec- distal to which fibres pass under the symphysis embedded in fibrous
tion shows the prostate situated literally in a basket of autonomic nerves tissue connecting the penile crura with the pubic arcuate ligament
(Costello et al 2004). The disposition of this basket may be altered as (Müller 1836).
a consequence of the development of benign prostatic hyperplasia, For years, patients undergoing radical prostatectomy for localized
which tends to favour a more posterolateral displacement of the neu- prostate cancer were almost always rendered impotent. Interest in pre-
rovascular bundles. Anteriorly, the top edges of the basket abut the serving potency was clear but the success rate was virtually nil; when it
lateral aspect of the dorsal vascular (venous) complex and the detrusor was reported, e.g. in radical perineal prostatectomy, the reason was
apron (Myers 2002b), both of which cover the anterolateral prostate. elusive (Finkle 1975). When surgery was the chosen method of treat-


Gross dissection demonstrates the rich abundance of nerves both later- ment, patients generally knew that erectile dysfunction or loss would
ally and posteriorly, with evident decussation of some nerves at the be likely to be an outcome in the quest to cure their cancer. This sad
prostato-urethral junction posteriorly (Costello et al 2004, Takenaka situation was to be reversed in the 1980s.
A B
Fig. 8.1.2 A–B, With the prostate removed, two neurovascular bundles (NVB), left and right, are shown as gross anatomical structures, isolated on the
rectal surface (R) as they course distally to embrace the transected striated sphincter (SS) and membranous urethra (U). Other abbreviations: B, bladder;
LA, levator ani; NVT, neurovascular triangle. (A, Adapted with permission from Myers RP, Cheville JC, Pawlina W; Making anatomic terminology of
the prostate and contiguous structures clinically useful: historical review and suggestions for revision in the 21st century. Clinical Anatomy. 2010
Jan;23(1):18–29. B, Used with permission of Mayo Foundation for Medical Education and Research.)


ThE NEuROvAsCulAR buNdlEs Of ThE pROsTATE
e74
8
NOITCEs
A B
Fig. 8.1.3 A–B, After haemostatic clips are applied to secure the prostate vascular pedicle, a scissor cut releases the left neurovascular bundle (NVB)
isolated by combined retrograde and anterograde dissection during robotic-assisted laparoscopic prostatectomy. Other abbreviations: B, bladder; NVT,
neurovascular triangle; P, prostate; SV, seminal vesicle. (A, Video frame courtesy of V. Patel, MD, FACS, University of Central Florida, Altamonte Springs,
Florida. Used with permission. B, Used with permission of Mayo Foundation for Medical Education and Research.)
Finding the reason for the dysfunction and the means of preventing with more functional profile, membranous urethral sphincteric length
it was the focus of attention of Walsh and Donker (1982), who inde- (Presti et al 1990). Pudendal innervation of the sphincter complex from
pendently reported the course of autonomic nerves running distally below is well recognized (Hollabaugh et al 1997), and patients under-
from the pelvic plexus, some of which became cavernous nerves of the going prostate removal with no preservation of their neurovascular
penis. Their work corroborated that of Müller (1836), who, on the basis bundles can experience perfect urinary control.
of dissecting two male cadavers, described a cavernous plexus that was The neurovascular bundles are important. In surgery, patients sub-
a continuation of the prostatic plexus; major and minor cavernous jected to the least injury by virtue of maintaining the full number and
nerves infiltrated the corpora cavernosa and corpus spongiosum, ulti- integrity of all neurovascular bundle-related autonomic nerves, as well
mately and intimately connecting in their terminal distribution to the as those disposed to be cavernous in destination, will do best in terms
penile helicine arteries that are responsible for erection. of recovery of their erectile function and, possibly, urinary control.
In surgery devised to preserve potency successfully (Quinlan et al Despite universal recognition by the urological community, neurovas-


1991), the neurovascular bundles must be dissected bilaterally away cular bundles have yet to be recognized in official anatomical nomen-
from the posterolateral aspects of the prostate (Fig. 8.1.3). As originally clature (International Anatomical Nomenclature Committee 1989,
defined and emphasized by Walsh and colleagues (1983), the critical Federative Committee on Anatomical Terminology 1998). With this in
technical step in preservation of the neurovascular bundles in radical mind, a suggestion has been offered to update terminology with the
prostatectomy is to ligate the vascular pedicles to the inferior bladder Latin fasciculus neurovascularis prostatae [dexter et sinister] and, in English,
and prostate in a line anterior to the course of the neurovascular neurovascular bundle of prostate [right and left] (Myers et al 2010). Official
bundles. When the procedure is done correctly, the result is a neuro- recognition of these grossly reproducible structures would put anatom-
vascular triangle on each side in the region of the vascular pedicle at ists, urologists, surgical pathologists and other students of anatomy on
the junction of the prostate and the seminal vesicles (see Figs 8.1.2 and the same page.
8.1.3) (Tewari et al 2006).
Any role of nerves within the neurovascular bundles controlling
Acknowledgement
urinary continence is controversial. Nerve fibres from the neurovascular
bundles that enter the striated urethral sphincter may be simply passing
through the sphincter to innervate the smooth muscle sphincter (lis- Patrick C Walsh MD, University Distinguished Service Professor,
sosphincter) of the membranous urethra. The idea that autonomic James Buchanan Brady Urological Institute, Johns Hopkins Hospital,
nerves would ever innervate the specialized striated and slow-twitch Professor Anthony J Costello MD FRACS FRCSI (Hon) MBBS, The
rhabdosphincter is particularly contentious. The fact that patients who Royal Melbourne Hospital, and Stephen W Carmichael PhD DSc,
have surgery with preservation of neurovascular bundles seem to do Professor Emeritus of Anatomy, Mayo Clinic, provided invaluable
better has never been separated from the confounder that they are left advice.
REFERENCES


Alsaid B, Bessede T, Diallo D et al 2011 Division of autonomic nerves within Eichelberg C, Erbersdobler A, Michl U et al 2007 Nerve distribution along
the neurovascular bundles distally into corpora cavernosa and corpus the prostatic capsule. Eur Urol 51:105–10.
spongiosum components: immunohistochemical confirmation with Federative Committee on Anatomical Terminology 1998 Terminologia Ana-
three-dimensional reconstruction. Eur Urol 59:902–9. tomica: International Anatomical Terminology. Stuttgart: Thieme.
Arai Y 2006 Anatomy for open radical prostatectomy and cystectomy. In: Finkle JE, Finkle PS, Finkle AL 1975 Encouraging preservation of sexual
Yoshida O, Arai Y, Matsuda T (eds) Anatomy for Urologic Surgery. function postprostatectomy. Urology 6:697–702.
Tokyo: Medical View; Ch. 7, pp. 142–55.
Hollabaugh RS Jr, Dmochowski RR, Steiner MS 1997 Neuroanatomy of the
Costello AJ, Brooks M, Cole OJ 2004 Anatomical studies of the neurovas- male rhabdosphincter. Urology 49:426–34.
cular bundle and cavernosal nerves. BJU Int 94:1071–6.
International Anatomical Nomenclature Committee 1989 Nomina Ana-
Costello AJ, Dowdle BW, Namdarian B et al 2011 Immunohistochemical tomica, 6th ed. Edinburgh: Churchill Livingstone.
study of the cavernous nerves in the periprostatic region. BJU Int 107:
Kaiho Y, Nakagawa H, Saito H et al 2009 Nerves at the ventral prostatic
1210–5.
capsule contribute to erectile function: initial electrophysiological
Durward A 1953 Fig. 967 Abdomino-pelvic plexuses in peripheral nervous assessment in humans. Eur Urol 55:148–54.
system. In: Brash JC (ed). Cunningham’s Textbook of Anatomy, 9th ed.
London: Oxford University Press, p. 1141.


The neurovascular bundles of the prostate
e75
1.8
YRATNEMMOC
Kiyoshima K, Yokomizo A, Yoshida T et al 2004 Anatomical features of Rocco F, Carmignani L, Acquati P et al 2007 Early continence recovery after
periprostatic tissue and its surroundings: a histological analysis of 79 open radical prostatectomy with restoration of the posterior aspect of
radical retropubic prostatectomy specimens. Jap J Clin Oncol 34: the rhabdosphincter. Eur Urol 52:376–83.
463–8. Schlegel PN, Walsh PC 1987 Neuroanatomical approach to radical cysto-
Lepor H, Gregerman M, Crosby R et al 1985 Precise localization of the prostatectomy with preservation of sexual function. J Urol 138:
autonomic nerves from the pelvic plexus to the corpora cavernosa: a 1402–6.
detailed anatomical study of the adult male pelvis. J Urol 133: Takenaka A, Murakami G, Matsubara A et al 2005 Variation in course of
207–12. cavernous nerve with special reference to details of topographic relation-
Lunacek A, Schwentner C, Fritsch H et al 2005 Anatomical radical retropubic ships near prostatic apex: histologic study using male cadavers. Urology
prostatectomy: ‘curtain dissection’ of the neurovascular bundle. BJU Int 65:136–42.
95:1226–31. Takenaka A, Soga H, Hinata N et al 2011 Classification of the distribution
Montorsi F, Salonia A, Suardi N et al 2005 Improving the preservation of of cavernous nerve fibers around the prostate by intraoperative electrical
the urethral sphincter and neurovascular bundles during open radical stimulation during laparoscopic radical prostatectomy. Int J Impot Res
retropubic prostatectomy. Eur Urol 48:938–45. 23:56–61.
Müller J 1836 Über die organischen Nerven der erectilen männlichen Gesch- Tewari A, Takenaka A, Mtui E et al 2006 The proximal neurovascular plate


lectsorgane des Menschen und der Säugethiere. Berlin: F. Dümmler. and the tri-zonal neural architecture around the prostate gland: impor-
Myers RP 2002a Gross and applied anatomy of the prostate. In: Kantoff PW, tance in the athermal robotic technique of nerve-sparing prostatec-
Carroll PR, D’Amico AV (eds) Prostate cancer: principles and practice. tomy. BJU Int 98:314–23.
Philadelphia: Lippincott Williams & Wilkins; Ch. 1, pp. 3–15. van der Zypen EM 1988 Composition and topographic anatomy of the
Myers RP 2002b Detrusor apron, associated vascular plexus, and avascular inferior hypogastric plexus (pelvic plexus). SANDORAMA III–IV:
plane: relevance to radical retropubic prostatectomy: anatomic and sur- 24–32.
gical commentary. Urology 59:472–9. Walsh PC, Donker PJ 1982 Impotence following radical prostatectomy:
Myers RP, Cheville JC, Pawlina W 2010 Making anatomic terminology of the insight into etiology and prevention. J Urol 128:492–7.
prostate and contiguous structures clinically useful: historical review Walsh PC, Lepor H, Eggleston JC 1983 Radical prostatectomy with preserva-
and suggestions for revision in the 21st century. Clin Anat 23:18–29. tion of sexual function: anatomical and pathological considerations.
Paick JS, Donatucci CF, Lue TF 1993 Anatomy of cavernous nerves distal to Prostate 4:473–85.
prostate: microdissection study in adult male cadavers. Urology 42: Walz J, Burnett AL, Costello AJ et al 2010 A critical analysis of the current
145–9. knowledge of surgical anatomy related to optimization of cancer control
Presti JC Jr, Schmidt RA, Narayan PA et al 1990 Pathophysiology of urinary and preservation of continence and erection in candidates for radical
incontinence after radical prostatectomy. J Urol 143:975–8. prostatectomy. Eur Urol 57:179–92.
Quinlan DM, Epstein JI, Carter BS et al 1991 Sexual function following


radical prostatectomy: influence of preservation of neurovascular
bundles. J Urol 145(5):998–1002.


Real-time microscopy of the upper and lower
COMMENTARY
gastrointestinal tract and the hepatobiliary–
8.2
pancreatic system during endoscopy
Martin Götz
Introduction
Real-time histology during ongoing endoscopy has been a goal of endos-
copists since the very beginning of modern endoscopy. Technological
advancements have brought forward endomicroscopy and endocytos-
copy, two microscopic techniques that provide high-resolution (sub)
cellular images of the mucosa with approximately 1000-fold magnifica-
tion in vivo (Goetz et al 2014). These novel techniques have been exten-
sively studied for diseases of the upper gastrointestinal tract and the
lower gastrointestinal tract, and also, more recently, for intrabiliary and
intrapancreatic imaging. Imaging relies on the application of fluorescent
agents (mostly fluorescein) for endomicroscopy or of topical dyes for
endocytoscopy.
Real-time virtual histology (‘optical biopsy’) serves several needs in
clinical medicine: first, it provides an immediate diagnosis for the well-
trained endoscopist. This limits the need for biopsies and helps to
minimize sampling error. Second, microscopic imaging can predict
depth of invasion of lesions or assist in guiding immediate endoscopic
resection. Third, endomicroscopy has also been successfully evaluated
for functional and molecular imaging of the gastrointestinal mucosa,
providing deep insights into normal tissue function and disease pathol-
ogy in translational research.
Technology and devices
For confocal laser endomicroscopy (CLE), two devices are available for
clinical use: in an endoscope-based approach (eCLE), a miniaturized
confocal scanner is integrated into the distal end of a dedicated endo-
scope, whereas in probe-based CLE (pCLE), a flexible probe can be
introduced into the working channel of different endoscopes (Fig.
8.2.1). eCLE provides images with higher resolution and user-adaptable
imaging plane depth. pCLE is more flexible for use ‘on demand’, and
thin probes can be introduced into the bile or pancreatic duct. Fluores-
cein is the contrast agent most commonly used (5 ml/10% intrave-
nously), together with blue laser light excitation, but – since fluorescein
does not stain nuclei – acriflavine and cresyl violet have also been
studied for topical application. CLE provides transverse optical sections,


i.e. orientated at 90° to conventional histopathology, at the tissue
surface or below (up to 250 µm).
Endocytoscopy is an adaption of contact white light microscopy with
lens-based magnification (‘ultrahigh zoom-endoscopy’). After intravital
tissue staining, high-resolution images of the uppermost mucosal layer
(including nuclei) are visible. Systems are currently not marketed, limit-
ing the broad clinical application of endocytoscopy.
Upper gastrointestinal tract
In the healthy upper gastrointestinal tract, squamous epithelium of the
oesophagus, gastric mucosa and duodenal villi can be easily visualized
and differentiated with CLE by their characteristic structural features,
Fig. 8.2.1 For endomicroscopy, two systems are available: for probe-
even without visualization of nuclei (Fig. 8.2.2). In Barrett’s oesopha-
based imaging (right), a thin confocal probe is used together with a
gus, the visualization of goblet cells is the hallmark of intestinal meta-
conventional endoscope; for endoscope-integrated imaging (left), a
plasia. Barrett’s-associated neoplasia was diagnosed in a pilot trial with miniaturized scanner is integrated into a dedicated endoscope (protruding
high accuracy (Kiesslich et al 2006) (Fig. 8.2.3). When compared to tip). See text for details.
untargeted quadrant biopsies, the yield per biopsy was significantly
higher when eCLE was used, and two-thirds of patients did not need
any biopsy based on normal optical biopsies (Dunbar et al 2009).
Similarly, pCLE had a high negative predictive value for Barrett’s In the stomach, studies have addressed the use of CLE to diagnose
oesophagus (Pohl et al 2008). Since pan-endomicroscopy of larger gastritis (Wang et al 2010), Helicobacter pylori (Kiesslich et al 2005),
mucosal regions is not feasible, CLE is often used in conjunction with intestinal metaplasia (Guo et al 2008), and gastric hyperplastic and
chromoendoscopy to pinpoint the region of interest to be examined adenomatous polyps (Li et al 2010). In a large trial, eCLE was able to


subsequently by CLE. In squamous cell carcinoma, eCLE was able to diagnose high-grade neoplasia and superficial gastric cancer in a high-
predict malignant histology in unstained regions after chromoendos- risk population of 1786 patients (Li et al 2011). CLE can also help to
e76 copy with Lugol’s solution (Pech et al 2008). guide intervention and minimize sampling error prior to resection


Real-time microscopy of the upper and lower gastrointestinal tract
e77
2.8
YRATNEMMOC
A B
C D
Fig. 8.2.2 Normal microscopic anatomy of the gastrointestinal tract. A, In the squamous cell lining of the oesophagus, intrapapillary capillary loops
(arrows) are orientated perpendicular to the tissue surface in a corkscrew fashion. Bright vessel contrast is found after intravenous fluorescein injection;
black dots within the vessel lumen correspond to unstained red blood cells. B, The gastric mucosa (antrum) typically shows a cobblestone-like surface
pattern; in subsurface sections, capillaries become visible (arrows). C, In the terminal ileum, the villi are easily seen. Below the columnar epithelium with
goblet cells (arrowheads), separated by the basal membrane, hairpin-like capillaries (arrows) can be seen within the lamina propria. D, The normal colon
shows crypts of fairly even size with an unstained (black) central lumen (arrows), surrounded by goblet cells with dark mucin inclusions (arrowheads) that
can be optically sectioned parallel (drop-like shape) or vertical (round shape) to the mucosa. Original magnification ×1000.
(Jeon et al 2011) or surveillance and reintervention after resection (Ji niques for prediction of histology, such as virtual chromoendoscopy
et al 2011). and high-definition endoscopy, but shows higher accuracy (Buchner
et al 2010).
Lower gastrointestinal tract Endocytoscopy has mostly been studied in the lower gastrointestinal
tract. A high accuracy and kappa agreement with histology have been
found for the diagnosis of colorectal lesions (Sasajima et al 2006).
The first study with eCLE in patients was performed in screening colon-
Endocytoscopy was non-inferior to histopathology but results were
oscopy, establishing criteria for normal mucosa, hyperplasia and neo-
available immediately (Mori et al 2013).
plasia (Kiesslich et al 2004) that were followed by a similar classification
system for pCLE (Kuiper et al 2011) (see Fig. 8.2.2). In ulcerative colitis,
Hepatobiliary and pancreatic system


combination of eCLE with chromoendoscopy found a four-fold increase
in the number of intraepithelial neoplasias with a 10-fold reduction
in biopsies compared to a quadrant biopsy protocol (Kiesslich et al Indeterminate biliary strictures pose a clinical dilemma and the
2007a), corroborating the concept of targeted, ‘smart’ biopsies for approach to obtain specimens for histopathology is often limited. CLE
optimized surveillance. CLE competes with non-microscopic tech- probes that are advanced into the bile duct via duodenoscopes have


REAL-TIME MICROSCOPY OF THE UPPER AND LOWER GASTROINTESTINAL TRACT
e78
8
NOITCES
A B
Fig. 8.2.3 A, In Barrett’s oesophagus, the normal squamous epithelium is replaced by specialized intestinal metaplasia that resembles mucosa of the
small intestine (compare Fig. 8.2.2C). The double lining at the surface of the villi (arrows) corresponds to the brush border, while black dots (arrowheads)
indicate mucin inclusions in goblet cells, establishing the diagnosis of Barrett’s oesophagus during endoscopy. B, In Barrett’s-associated neoplasia
(same patient), the tissue structure is progressively lost. Residual gland structures are visible (arrows), and white contrast extravasation into the solid
tissue indicates increased vessel leakiness of tumour-associated neoangiogenesis. Original magnification ×1000.
demonstrated increased sensitivity in a first trial (Meining et al 2008). function. Similarly, in patients with H. pylori-associated gastritis, epithe-
Such thin CLE probes were also used for imaging in the pancreatic duct lial barrier damage was predominant: failure to reverse barrier function
(Meining et al 2012) and were advanced through needles targeted by indicated complications despite H. pylori clearance (Ji et al 2012).
endoscopic ultrasonography to pancreatic cystic lesions (Konda et al CLE has also been used for molecular imaging (Atreya and Goetz
2011). Rigid laparoscopic CLE devices have been used for microscopic 2013). Fluorescent labelling of single molecules highlighted adenoma-
liver imaging (Goetz et al 2010a). Interpretation of images from the tous lesions in patients (Hsiung et al 2008, Liu et al 2013). Targeting
hepatobiliary and pancreatic systems is less straightforward since struc- of specific surface receptors overexpressed on malignant cells has been
tural resolution is lower than in the gastrointestinal tract. The final used as a molecular beacon for colorectal (Goetz et al 2010b) and
clinical significance, therefore, remains to be established in larger trials. gastric cancers (Hoetker et al 2012) in murine models, and has been
linked to predicting response to targeted therapy (Goetz et al 2013). It


Perspective is too early to integrate these results into routine clinical protocols.
However, they indicate a way to individualizing therapy based on func-
tional and molecular microscopic imaging.
The introduction of CLE has augmented translational research. To date,
no other device is able to study microscopic events dynamically in the
Summary
natural micromilieu, free of artefacts and without disrupting tissue
integrity or perfusion. CLE was able to visualize intramucosal bacteria
in patients with inflammatory bowel diseases (IBD) (Moussata et al In the past 10 years, microscopic imaging during endoscopy has become
2011), exemplifying the high resolution that can be obtained in vivo. possible, and multiple trials have evaluated its relevance in imaging in
Gaps smaller than a single cell, punctuating the epithelial barrier of the the upper and lower gastrointestinal tracts and, recently, within the
healthy gut mucosa can be visualized, and probably correspond to hepatobiliary and pancreatic systems. Optical biopsies by microscopic
residual microlesions after normal cell shedding (Kiesslich et al 2007b). imaging have not replaced (or aimed at replacing) tissue sampling, but
Increased shedding was found in IBD (Liu et al 2011). Functional can help to target, complement or avoid conventional biopsies, decide
impairment of such gaps in endoscopically and histopathologically on and guide endoscopic resection and, broaden our understanding of
normal mucosa predicted IBD flares (Kiesslich et al 2012), potentially microarchitectural and molecular processes within the mucosa of the
constituting the microarchitectural correlate of the impaired barrier gastrointestinal tract.
REFERENCES
Atreya R, Goetz M 2013 Molecular imaging in gastroenterology. Nat Rev Goetz M, Hoetker MS, Diken M et al 2013 In vivo molecular imaging
Gastroenterol Hepatol 10:704–12. with cetuximab, an anti-EGFR antibody, for prediction of response in
Buchner AM, Shahid MW, Heckman MG et al 2010 Comparison of probe- xenograft models of human colorectal cancer. Endoscopy 45:469–77.
based confocal laser endomicroscopy with virtual chromoendoscopy for Goetz M, Malek NP, Kiesslich R 2014 Microscopic imaging in endoscopy:


classification of colon polyps. Gastroenterology 138:834–42. endomicroscopy and endocytoscopy. Nat Rev Gastroenterol Hepatol
Dunbar KB, Okolo P 3rd, Montgomery E et al 2009 Confocal laser endomi- 11:11–18.
croscopy in Barrett’s esophagus and endoscopically inapparent Barrett’s Guo YT, Li YQ, Yu T et al 2008 Diagnosis of gastric intestinal metaplasia
neoplasia: a prospective, randomized, double-blind, controlled, cross- with confocal laser endomicroscopy in vivo: a prospective study. Endos-
over trial. Gastrointest Endosc 70:645–54. copy 40:547–53.
Goetz M, Deris I, Vieth M et al 2010a Near-infrared confocal imaging during Hoetker MS, Kiesslich R, Diken M et al 2012 Molecular in vivo imaging of
mini-laparoscopy: a novel rigid endomicroscope with increased imaging gastric cancer in a human-murine xenograft model: targeting epidermal
plane depth. J Hepatol 53:84–90. growth factor receptor. Gastrointest Endosc 76:612–20.
Goetz M, Ziebart A, Foersch S et al 2010b In vivo molecular imaging of Hsiung PL, Hardy J, Friedland S et al 2008 Detection of colonic dysplasia
colorectal cancer with confocal endomicroscopy by targeting epidermal in vivo using a targeted heptapeptide and confocal microendoscopy. Nat
growth factor receptor. Gastroenterology 138:435–46. Med 14:454–8.


Real-time microscopy of the upper and lower gastrointestinal tract
e79
2.8
YRATNEMMOC
Jeon SR, Cho WY, Jin SY et al 2011 Optical biopsies by confocal endomi- Li WB, Zuo XL, Li CQ et al 2011 Diagnostic value of confocal laser endomi-
croscopy prevent additive endoscopic biopsies before endoscopic croscopy for gastric superficial cancerous lesions. Gut 60:299–306.
submucosal dissection in gastric epithelial neoplasias: a prospective, Liu J, Zuo X, Li C et al 2013 In vivo molecular imaging of epidermal growth
comparative study. Gastrointest Endosc 74:772–80. factor receptor in patients with colorectal neoplasia using confocal laser
Ji R, Zuo XL, Li CQ et al 2011 Confocal endomicroscopy for in vivo predic- endomicroscopy. Cancer Lett 330:200–7.
tion of completeness after endoscopic mucosal resection. Surg Endosc Liu JJ, Wong K, Thiesen AL et al 2011 Increased epithelial gaps in the small
25:1933–8. intestines of patients with inflammatory bowel disease: density matters.
Ji R, Zuo XL, Yu T et al 2012 Mucosal barrier defects in gastric intestinal Gastrointest Endosc 73:1174–80.
metaplasia: in vivo evaluation by confocal endomicroscopy. Gastroin- Meining A, Frimberger E, Becker V et al 2008 Detection of cholangiocarci-
test Endosc 75:980–7. noma in vivo using miniprobe-based confocal fluorescence microscopy.
Kiesslich R, Burg J, Vieth M et al 2004 Confocal laser endoscopy for diagnos- Clin Gastroenterol Hepatol 6:1057–60.
ing intraepithelial neoplasias and colorectal cancer in vivo. Gastroen- Meining A, Shah RJ, Slivka A et al 2012 Classification of probe-based con-
terology 127:706–13. focal laser endomicroscopy findings in pancreaticobiliary strictures.
Kiesslich R, Goetz M, Burg J et al 2005 Diagnosing Helicobacter pylori in vivo Endoscopy 44:251–7.


by confocal laser endoscopy. Gastroenterology 128:2119–23. Mori Y, Kudo S, Ikehara N et al 2013 Comprehensive diagnostic ability of
Kiesslich R, Gossner L, Goetz M et al 2006 In vivo histology of Barrett’s endocytoscopy compared with biopsy for colorectal neoplasms: a pro-
esophagus and associated neoplasia by confocal laser endomicroscopy. spective randomized noninferiority trial. Endoscopy 45:98–105.
Clin Gastroenterol Hepatol 4:979–87. Moussata D, Goetz M, Gloeckner A et al 2011 Confocal laser endomicros-
Kiesslich R, Goetz M, Lammersdorf K et al 2007a Chromoscopy-guided copy is a new imaging modality for recognition of intramucosal bacteria
endomicroscopy increases the diagnostic yield of intraepithelial neopla- in inflammatory bowel disease in vivo. Gut 60:26–33.
sia in ulcerative colitis. Gastroenterology 132:874–82. Pech O, Rabenstein T, Manner H et al 2008 Confocal laser endomicroscopy
Kiesslich R, Goetz M, Angus EM et al 2007b Identification of epithelial gaps for in vivo diagnosis of early squamous cell carcinoma in the esophagus.
in human small and large intestine by confocal endomicroscopy. Gas- Clin Gastroenterol Hepatol 6:89–94.
troenterology 133:1769–78. Pohl H, Rosch T, Vieth M et al 2008 Miniprobe confocal laser microscopy
Kiesslich R, Duckworth CA, Moussata D et al 2012 Local barrier dysfunction for the detection of invisible neoplasia in patients with Barrett’s
identified by confocal laser endomicroscopy predicts relapse in inflam- oesophagus. Gut 57:1648–53.
matory bowel disease. Gut 61:1146–53. Sasajima K, Kudo SE, Inoue H et al 2006 Real-time in vivo virtual histology
Konda VJ, Aslanian HR, Wallace MB et al 2011 First assessment of needle- of colorectal lesions when using the endocytoscopy system. Gastrointest


based confocal laser endomicroscopy during EUS-FNA procedures of Endosc 63:1010–17.
the pancreas (with videos). Gastrointest Endosc 74:1049–60. Wang P, Ji R, Yu T et al 2010 Classification of histological severity of Helico-
Kuiper T, van den Broek FJ, van Eeden S et al 2011 New classification for bacter pylori-associated gastritis by confocal laser endomicroscopy. World
probe-based confocal laser endomicroscopy in the colon. Endoscopy J Gastroenterol 16:5203–10.
43:1076–81.
Li WB, Zuo XL, Zuo F et al 2010 Characterization and identification of gastric
hyperplastic polyps and adenomas by confocal laser endomicroscopy.
Surg Endosc 24:517–24.


CHAPTER Pelvic girdle and lower limb: overview
78
and surface anatomy
The structure of the lower limb is specialized for support of the body’s limb, which is especially important to physicians during various surgi-
weight, locomotion, and maintenance of body stability (balance). cal and clinical procedures.
Indeed, adaptations for weight-bearing and stability account for the
major structural and functional differences between the upper and
lower limbs. The inguinal (pelvicrural) and gluteal (buttock) regions SKIN, FASCIA AND SOFT TISSUES
are important anatomical junctional zones between the trunk and the
lower limb through which longitudinally running nerves and vessels
In the young adult and as an adaptation to weight-bearing, the skin of
travel (Fig. 78.1). The inguinal region includes the transitional zones
the lower limb is generally stronger and thicker than that of the upper
between the lower limb and abdominal cavity via the myopectineal
limb. The soft tissues of the sole of the foot are particularly thickened
orifice (the gap between the inguinal ligament and hip joint) and
in order to support weight during standing. The skin of the buttocks
inguinal canal, and provides a gateway for the passage of various struc-
and posterior thigh bears weight in the sitting position, and conse-
tures. Similarly, the obturator canal allows for the obturator nerve and
quently is relatively thick. The skin over the anteromedial aspect of the
vessels to traverse between the pelvis and thigh. The gluteal region com-
leg is particularly fragile and vulnerable in the elderly.
municates with the lower limb and the abdominopelvic cavity via the
greater sciatic foramen, and with the lower limb and pelvic cavity and
Subcutaneous tissue (tela subcutanea)
perineum via the lesser sciatic foramen.
This chapter will provide general information on the lower limb in
two sections. The first section is an overview of the general organization The subcutaneous tissue (tela subcutanea; hypodermis) of the lower
of the lower limb, with particular emphasis on the fasciocutaneous limb becomes thinner peripherally. It participates in the integrity of the
system, distribution of the major blood vessels and lymphatic channels, skin and provides support for subcutaneous structures such as super-


and the branches of the lumbar and sacral plexuses; it is intended to ficial veins and cutaneous nerves. It is connected to the adventitia of
complement the detailed regional anatomy described in Chapters the superficial veins by thin bands that prevent the displacement of the
80–84. The second section describes the surface anatomy of the lower veins during movement. The hypodermal plexus of arteries and veins
Greater sciatic foramen above piriformis:
Superior gluteal nerve, artery, vein
Sacrotuberous ligament
Piriformis
Sacrospinous ligament
Lesser sciatic foramen:
Obturator internus tendon
Pudendal nerve and internal pudendal
vessels pass into perineum
from gluteal region
Greater sciatic foramen below
piriformis:
Sciatic nerve Inguinal canal
Inferior gluteal nerve, artery, vein
Pudendal nerve Obturator canal:
Internal pudendal artery and vein Obturator nerve
Posterior femoral cutaneous nerve Obturator vessels
Nerve to obturator internus
Nerve to quadratus femoris
Gap between inguinal
ligament and pelvic bone:
Psoas major, iliacus,
pectineus
Femoral artery
Femoral vein
Lymphatics
Femoral branch of
genitofemoral nerve
Lateral femoral
cutaneous nerve
Fig . 78 .1 Gateways from the abdomen, pelvis and perineum to the lower limb . (With permission from Drake RL, Vogl AW, Mitchell A (eds), Gray’s
1316 Anatomy for Students, 2nd ed, Elsevier, Churchill Livingstone . Copyright 2010 .)


Skin, fascia and soft tissues
1317
87
RETPAHC
controls blood flow through the skin, thus helping to regulate body Fasciocutaneous system
temperature (Sterzi 1910). The fascial septa dictate the pathways of cutaneous arteries, which sub-
The deep fascia of the lower limb is a well-defined layer that forms sequently perforate and ramify on the fascial ‘stocking’ before supplying
a tough circumferential ‘stocking-like’ structure that constrains the mus- the skin.
culature (Fig. 78.2). Septa pass from the deep surface of this fascial
sheath to the bones within, confining the functional muscle groups Osteofascial compartments in the lower limb
within osteofascial compartments. The tough fascia gives additional The muscles of the thigh may be grouped into three compartments
areas of attachment to the muscles and ensures maximal function. according to their function: namely, anterior (extensor), posterior
According to Cruveilhier (1841), all aponeurotic fasciae are put under (flexor) and medial (adductor). Only the anterior and posterior com-
tension by specific myofascial expansions or dedicated muscles. Such partments possess distinct fascial boundaries. A very definite fascial
thickenings may act functionally as additional tendons. Elsewhere, separation into anterior (extensor), posterior (flexor) and lateral
thickenings in the fascial skeleton form fibrous retinacula where (evertor) compartments exists in the leg, and compartment syndrome
tendons cross joints. The pattern of soft tissue organization has a is most common in this region (see below). Osteofascial compartments
bearing on the physiological effects of the muscles and is crucial for in the foot are described on page 1420.
efficient venous return from the limb. The fascial planes also control Vessels and nerves run through all the osteofascial compartments
and direct the spread of pathological fluids (blood, pus) within the and supply the muscles contained within them. The muscles acting
limb and play an important part in determining the degree and direc- within these closed compartments assist in maintaining the anti-gravity
tion of displacement seen in long bone fractures. flow of venous blood.
A Anterior superior iliac spine B
lliac crest
Inguinal ligament
Tensor fasciae latae
Spermatic cord


Saphenous opening, cribriform fascia Superior horn Gluteal fascia
Falciform margin
Inferior horn
Tensor fasciae latae
Long saphenous vein
Iliotibial tract
Gluteal fold
Fascia lata
Iliotibial tract
Tendon of quadriceps femoris
Fascia lata
Patella
Subcutaneous prepatellar bursa Lateral patellar retinaculum
Patellar ligament
Fibula, head
Subcutaneous infrapatellar bursa Tendon of biceps femoris Popliteal fossa
Deep fascia of leg
Tibia, anterior border
Gastrocnemius
Deep fascia of leg
Tibia, medial surface
Tendon of tibialis anterior
Tendon of gastrocnemius
Superior extensor retinaculum
Inferior extensor retinaculum
Extensor hallucis brevis Tendons of extensor digitorum longus
Tendon of extensor hallucis longus Calcaneal tendon Medial malleolus
Dorsal fascia of foot
Fig . 78 .2 The deep fascia of the lower limb . A, Anterior view . B, Posterior view . (With permission from Waschke J, Paulsen F (eds), Sobotta Atlas of
Human Anatomy, 15th ed, Elsevier, Urban & Fischer . Copyright 2013 .)


PElvIC GIRdlE ANd lOwER lImb: OvERvIEw ANd SuRFACE ANATOmy
1318
9
NOITCES
Compartment syndrome The fascial boundaries that limit the A B
osteofascial compartments are largely inelastic, which means that any Ilium
condition that leads to an increase in the volume of the compartmental
contents, e.g. muscle swelling caused by trauma, haemorrhage or local
infection, is likely to cause an increase in intracompartmental pressure.
If unrelieved, this increased pressure will lead to compressive occlusion
Sacrum
of the vessels in the compartment and consequent ischaemic damage
to the nerves and muscles of the compartment, a phenomenon known Pubis
as compartment syndrome. The normal compartmental pressure of
Coccyx
the leg is significantly higher in children than in adults: the average
pressure in the compartments varies between 13.3 and 16.6 mmHg in
Ischium
children, compared with 5.2 and 9.7 mmHg in adults (Staudt et al
2008).
The treatment of compartment syndrome relies on reducing abnor-
mally elevated tissue pressure. Surgical decompression of the restricting
compartment’s fasciae may be necessary; in order to prevent neurovas-
cular injury during a fasciotomy, the exact course of the nerves and
vessels within the affected compartment must be known (Apaydin et al
2008).
Femur
BONES AND JOINTS
The bones of the lower limb are the three fused components of the
pelvic girdle; the femur and patella (thigh); the tibia and fibula (leg);
and the tarsus, metatarsus, phalanges and sesamoid bones (foot) (Fig.
78.3). The pelvic bones (especially the ilium and ischium), femur, tibia
and bones of the hindfoot are strong and their external (cortical) and
internal (trabecular) structure is adapted for weight-bearing. Patella
The pelvic girdle connects the lower limb to the axial skeleton via
the sacroiliac joint, a plane synovial type of joint in which mobility has
been sacrificed for stability and strength, to allow for effective weight
transmission from the trunk to the lower limb. Anteriorly, the pelvic


girdle articulates with the contralateral girdle at the pubic symphysis, a
secondary cartilaginous joint that may display a slight degree of mobil-
ity during hip and sacroiliac movement, and during childbirth. The hip Tibia
joint, a synovial ball-and-socket joint, exhibits a very effective compro-
mise between mobility and stability that allows movement in all three
orthogonal planes. The more distal joints have gained mobility at the Fibula
expense of stability. The knee joint is a bicompartmental synovial artic-
ulation, which occurs mainly between the femur and the tibia, and
allows flexion, extension and some medial and lateral rotation of the
leg. It is not a true hinge joint because its axes of flexion and extension Talus
are variable and there is coupled rotation. The knee joint also includes
the articulation between the patella and femur. The tibia and fibula Calcaneus
articulate with each other at the superior and inferior tibiofibular joints. Navicular
The superior joint, a plane synovial joint, allows slight gliding move-
ment only. The inferior joint, a fibrous joint, lies just above the ankle Medial cuneiform
and allows a degree of fibular rotation linked to ankle motion. The
ankle (talocrural) joint is formed by the distal ends of the tibia and Metatarsal
fibula ‘gripping’ the talus, and allows dorsiflexion and plantar flexion.
There are multiple joints in the foot that may be classified topograph-
Phalanges
ically on the basis of whether they are in the hindfoot, midfoot or
forefoot. Collectively, these joints allow the complex movements
required as the foot fulfils its functional roles as a platform for standing
and for shock absorption and propulsion in gait.
Fig . 78 .3 An overview of the bones of the lower limb . A, Posterior aspect .
Both the knee and ankle are commonly subject to closed injuries,
B, Anterior aspect .
and the relatively superficial location of the knee renders it susceptible
to open injury and infection. Although the ankle is frequently injured
and is a major load-bearing joint, the incidence of clinically significant limb contains many muscles that act on more than one joint, and it is


degenerative arthritis is surprisingly low when compared with that unusual for any joint of the lower limb to move in isolation.
found in the hip and knee joints. Muscles of the lower limb may be subdivided into those of the iliac
and gluteal regions, and those of the thigh, leg and foot. Note that in
anatomical nomenclature, ‘leg’ refers to that part of the lower limb
MUSCLES
between the knee and ankle. The main muscles of the posterior abdomi-
nopelvic region are psoas major and iliacus (together called iliopsoas),
The effects of extension and medial rotation of the limb that occur the major flexors of the hip that run from the lumbar spine and inner
during fetal development are manifest in the relative positions of the surface of the ilium, respectively, to attach distally on to the lesser tro-
muscle groups in the thigh and the leg, and in the adult pattern of chanter of the femur. When present, the much less important psoas
segmental cutaneous innervation (dermatomes). The role of the muscles minor runs from the lumbar spine to the pubis. The muscles of the
of the lower limb in the maintenance of equilibrium during locomo- gluteal region include the three named gluteal muscles and the deeper
tion and in stance is rarely emphasized sufficiently. Many of the muscles short lateral rotators of the hip joint. Gluteus maximus lies most super-
act frequently or predominantly from their distal attachments. During ficially, running from the posterior pelvis to the proximal femur and
both stance and locomotion, the distal attachment is often fixed and fascia lata. It is a powerful extensor of the hip joint, acting more often
the proximal attachment is mobile, e.g. the predominant action of to extend the trunk on the femur than to extend the limb on the trunk.
gluteus medius is as a pelvic stabilizer rather than as a hip abductor. In Gluteus medius and minimus, attaching proximally to the outer surface
contrast, in the upper limb, the proximal muscle attachments are of the ilium and distally to the greater trochanter of the femur, are
usually fixed and the distal attachments are mobile, an arrangement abductors of the hip; their most important action is to stabilize the


that is consistent with the prehensile function of the hand. The lower pelvis on the femur during locomotion, and they are helped in this


vascular supply and lymphatic drainage
1319
87
RETPAHC
function by tensor fasciae latae, a more anteriorly placed muscle that may reveal decreased distal pulses (e.g. of the posterior tibial artery),
arises from the anterolateral ilium and inserts via the iliotibial tract on pallor or a cool extremity.
to the proximal tibia. Two of the short lateral rotators of the hip, piri-
formis and obturator internus, arise from within the pelvis, while the Arterial perforators of the lower limb
others, obturator externus, the gemelli and quadratus femoris, originate
and surgical flaps
externally; all of these muscles are attached distally to the proximal
femur.
The muscles of the thigh lie in three functional compartments. The Achieving adequate and aesthetically satisfactory skin and soft tissue
anterior or extensor compartment includes sartorius and the quadriceps cover for large, superficial tissue defects is a perennial challenge in the
femoris. Sartorius and rectus femoris are attached proximally to the field of plastic and reconstructive surgery, and accounts for a substantial
pelvis and can thus act on the hip joint as well as on the knee, whereas part of the plastic surgeon’s workload. Generally, split-thickness and
the vasti are attached proximally to the femoral shaft and, acting as a full-thickness skin grafts are suitable only for very superficial defects. To
unit, are powerful knee extensors. The medial or adductor compartment achieve tissue coverage for deeper and larger tissue defects, the plastic
contains the named adductor muscles and gracilis; pectineus may also surgeon employs one of a variety of autologous tissue flaps. A fascio-
be included. These muscles are attached proximally to the anterior cutaneous flap is composed of skin, fat and deep fascia (fascia muscul-
aspect of the pelvis, and distally to the femur; gracilis has no femoral orum); a lower-extremity fasciocutaneous flap (Pontén 1981) is very
attachment, being attached distally to the proximal tibia, while a part useful in the repair of soft tissue defects of the leg.
of adductor magnus has a proximal attachment to the ischial tuberosity. The viability of a flap transplanted from one part of the body to


The posterior compartment includes semitendinosus, semimembrano- another is crucially dependent on the flap’s blood supply. An apprecia-
sus and biceps femoris. These muscles are attached proximally to the tion of the angiosome concept, coupled with technological advances in
ischial tuberosity and act both to extend the trunk on the femur and to reconstructive microsurgery, has stimulated the development and use
flex and rotate the knee. Adductor magnus, as may be inferred from the of perforator (or perforator-based) flaps. These are flaps of skin or sub-
extent of its proximal attachment and its dual innervation, shares the cutaneous tissue supplied by one or more fascial ‘perfora tors’, i.e. arter-
first of these functions with the hamstrings. Biceps femoris is the only ies, which reach the suprafascial plexus either directly from a source
muscle of the thigh that is attached distally to the fibula, and has no vessel, or indirectly from some other neighbouring tissue (Harry et al
tibial attachment. 2009) (Fig. 78.6). Perforator-based flaps are typically harvested with
In the leg, the anterior or extensor compartment includes the exten- sparing of underlying muscle tissue and minimal trauma; their use
sors (dorsiflexors) of the foot and the extrinsic extensors of the toes. is said to reduce postoperative pain, donor site morbidity and func-
Tibialis anterior, the main foot dorsiflexor, also inverts the foot at the tional loss.
subtalar joint, while the smallest muscle of the compartment, fibularis The lower limb is the largest donor site in the body for perforator-
(peroneus) tertius, is a dorsiflexor that everts the foot. The posterior or based flaps. Commonly used flaps include anterolateral thigh flaps,
flexor (plantar flexor) compartment has superficial and deep compo- which provide a large amount of skin; superior and inferior gluteal
nents. The superficial component contains gastrocnemius and soleus, artery perforator flaps used in breast reconstruction; vascularized fibular
powerful plantar flexors of the foot, and the small plantaris with its flaps for reconstruction of deficient bone; vascularized tensor fasciae


long slender tendon. Gastrocnemius and soleus are attached distally to latae flaps for tendon reconstruction; vascularized sural nerve flaps for
the foot via the calcaneal (Achilles) tendon. The deep component of nerve reconstruction; and the gracilis muscle flap, used in, for example,
the flexor compartment contains popliteus, a rotator of the knee; the reanimation of paralysed muscle.
extrinsic flexors of the toes; and tibialis posterior, the main invertor of In the context of perforator flap surgery, the lower limb may be
the foot. The lateral compartment contains the main evertors of the considered in terms of four anatomic regions: gluteal; anterior hip and
foot, fibularis (peroneus) longus and brevis; both muscles are also thigh; knee and leg; and ankle and foot. Each lower limb accounts for
plantar flexors of the foot. Gastrocnemius and plantaris are attached approximately 23% of the total body surface area (thigh 10.5%, leg
proximally to the femur and distally to the calcaneus; these two muscles 6.5%, buttock 2.5% and foot 3.5%) and contains an average of 90 art-
can therefore act on the knee as well as at the ankle. The intrinsic erial perforators (Fig. 78.7).
muscles of the sole of the foot are arranged in four layers. They facilitate
the actions of the extrinsic flexors of the toes, and provide subtle
changes in the shape of the foot, thereby contributing to the control of VEINS
foot posture in stance and locomotion.
The veins of the lower limb can be subdivided, like those of the upper
limb, into superficial and deep groups (Figs 78.8–78.9). The superficial
VASCULAR SUPPLY AND LYMPHATIC DRAINAGE
veins lie in the subcutaneous tissue; the deep veins (deep to the deep
fascia) accompany the major arteries. Valves are present in both groups,
ARTERIES but are more numerous in the deep veins and are more numerous in
the veins of the lower versus the upper limb. Venous plexuses occur
The femoral artery (the continuation of the external iliac artery) pro- within and between some of the lower limb muscles. The two principal