Conception, Fetoplacental Unit

Conception
Onset of pregnancy (marked by mpantaton of bastocyst nto
endometrum)
Formaton of a vabe zygote
Sperm & Egg Transports
Estrogen - Functions
Capacitation - Readying the sperm
Sperms cannot fertze oocytes when they are newy e|acuated
Process of capactaton takes 5-7h
Capactated sperms are more actve
Locaton - capactaton occurs n uterus, ovducts
(factated by substances of femae genta tract)
Acrosoma reacton cannot occur unt capactaton has occurred
Remova of ateraton of surface moecuar on sperm membrane
Acqure energy (gucose, pyruvate)
Estrogen domnated uterus s optma for capactaton
Capactaton aows
Energy metabosm
Enhanced motty
Acrosome reacton to occur
Acrosome Reactions
Reacton that occurs n acrosome of sperm as t approaches egg
Sperm Penetration
When sperm reaches zona peucda
Attachment - oose assocaton
Bndng - strong attachment
Acrosome reacton
Penetraton of zona peucda by sperm
When acrosome reacton occurs, proteoytc enzymes are
exposed/ reeased
Fertilization
Acrosome reacton
J
Sperm come nto contact wth corona radata (oocyte)
Perforatons deveop n acrosome
Externa acrosome membrane ysed (Ca2+-nduced pont
fusons)
J
Cortca reacton
( ovum Ca2+ uptake)
(enzyme-contanng cortca granues are extruded from ovum)
J
Wthn 11h foowng fertzaton
Oocyte extruded a poar body wth ts excess chromosomes
J
Zygote
Passage of sperm through corona radata, depend on
Hyaurondase reeased from sperm acrosome
Tuba mucosa enzymes
Fagea acton - ads corona radata penetraton
Penetraton of zona peucda around oocyte - acrosoma
enzymes
Esterases
Acrosn
Neuramndase
Cortca reacton
Makes zona peucda mpermeabe to other sperms
When > 1 sperm manage to enter ovum, fetus neary
aways aborts
Dspermy = 2
Trpody = 3
Competed wthn 24h ovuaton
400-600 mon sperms are deposted at cervca openng
durng e|acuaton
Human sperms do not survve > 48h n femae genta tract
200 sperms reach fertzaton ste
Most degenerated
Absorbed by femae genta tract
Results of Fertilization
Stmuates secondary oocyte to compete meoss
Restore norma dpod number of chromosome (46)
Varaton of human speces (materna + paterna chromosomes
mx together)
Embryo contans ony materna mtochondra
(sperm mtochondra are dspersed nto egg cytopasm,
dscarded)
Sex of embryo determned - sex chromosome (Y or X) by sperm
Sperm wth X chromosome are more robust (ast onger)
If ntercourse before ovuaton ( chance of baby gr)
Robust (X-chromosome are stored)
Weaker (Y-chromosome de off)
Stages of Development - Early Embryo
lmplantation
Trophoblasts proliferate - form 2 dstnct ayers
Cytotrophoblast Syncytiotrophoblast
Ces of nner ayer
(retan ther ce boundares)
Ces n outer ayer
(ose pasma membranes)
(nvade endometrum)
Consequences of lmplantation
Vascuar permeabty n stroma tssue (underyng fetus)
Edema n nterceuar matrx
Sweng of stroma ces wth accumuaton of gycogen
granues
Progressve sproutng, ngrowths of capares
Decidualization
Prepares ma|or materna component of pacenta (the decdua)
lmplantation
Infammatory process - cytokne nducton of adheson moecue
expresson n endometra ces
lnvasion
Requres enzymatc (protenases, metaoprotenases,
coagenases, geatnases, stromeysns, metaoastases,
uroknase) dgeston of extra ceuar matrx wth smutaneous
contro of homeostass, angogeness
Placenta
Originates from
Maternal decidua basalis Chorion frondosum
Endometra tssue Embryonc trophobastc
tssues
Fetus, Uterus, Placenta
Hormonal Changes During Pregnancy
hCG (Human Chorionic Gonadotropin)
Produced by syncytotrophobastc ces
Detected as eary as 6-8 days after ovuaton n pasma
Produced by a types of trophobastc tssues
Hydatdform moe
Invasve moe
Chorocarcnoma
Physoogca roes
Mantan CL (corpus uteum) fe span
(beyond ts usua 2 to 6-7 weeks)
Stmuate CL (corpus uteum) to produce progesterone,
estrogen, reaxn
Maternal Responses to hCG
hPL (Human Placental Lactogen)
hCS (Human Chorionic Somatomammotropin)
Physiological roles
Stmuates synthess of mk protens, bone growth
J Senstvty of ces to nsun (skeeta musces)
Mobzes fat from adpose tssue
(gucose spared for use by fetus, FFA to meet materna
metaboc needs)
Estrogen
Feta adrena provdes DHEA(s) - precursor for pacenta
producton of
Estrone
Estrado
Syntheszed from feta, materna androgens
Pacenta cannot convert progesterone androgens
Physiological roles
Stmuate uterne bood fow - mantan favourabe ntrauterne
envronment
Prepare ducta breast deveopment for actaton
Impact on other hormona system (RAA, SHBG, TBG)
Feta deveopment, organ maturaton - capacty for feta ung
surfactant
Causes reaxaton, softenng of materna pevc gaments,
symphyss pubs
LDL choestero uptake, actvty of P450 enzyme
Progesterone
An absoute requrement for preparaton, mantenance of
pregnancy
Physiological roles
Stmuates faopan tubes, endometra gands
Secrete nutrents (on whch zygote depends)
Mantan decdua nng of uterus
Inhbts uterne contracton
Inhbt producton of PG
J Senstvty to oxytocn - prevent premature expuson of
fetus
Stmuate deveopment of aveoar pouches of mammary gands
( capacty to secrete mk)
Inhbt materna mmune responses to antgen from fetus
Prevent re|ecton
Suppress T-ymphocyte-nduced cytotoxcty
Stmuates respratory center - ventaton
(Dspose of CO2 produced by pregnant woman, fetus)
Development of Female Genital System

Development of Female Genital System
Gonads Genital Ducts
Indifferent stage of sexual
development
Indifferent stage
Female genital ducts, Auxiliary genital
glands Primordial germ cells
Sex determination

Development of Gonads (Testis & Ovaries)
Mesodermal epithelium (mesothelium)
Underlying mesenchyme
Primordial germ cells


Indifferent Gonads Gonadal ridge
At 5
th
week, before & during arrival of germ cells
Proliferation of underlying mesenchyme (from medial side of mesonephros)
Proliferation of mesodermal epithelium lining posterior abdominal wall
y Penetrate underlying mesenchyme
y Form primary sex cords
Produce bulge called gonadal ridge

Indifferent Gonads Primary Sex Cords
Connected to surface epithelium
Cannot differentiate between male, female
Indifferent gonads stage before 7
th
week

Consists of
y Outer cotex
y Inner medulla
Sex Chromosome
XX XY
Cortex differentiates into ovary Medulla differentiates into testis
Medulla regresses Cortex regresses




Indifferent Gonads Primordial Germ Cells
Origin - Endodermal cells of yolk sac (near origin of allantois)
During folding of embryo (5
th
week)
y Dorsal part of yolk sac is incorporated into embryo
y Primary germ cells migrate by amoeboid movement via dorsal mesentery
of hindgut to gonadal ridges
6
th
week
y Invade gonadal ridge
y Incorporated into primary sex cords
y Form oogonia


Influence of Primordial Germ Cells on Indifferent Gonad




Effects of Primordial Germ Cells on Indifferent Gonad

Y chromosome has strong testis-determining effect
Androgen testosterone produced by testis determines maleness

Development of Ovaries
Primitive Sex Cords
Secondary Sex Cords
(Cortical Cords)
Do not become prominent in female
embryo
(Male Seminiferous tubules)
Extends from surface epithelium
(mesodermal epithelium)
into underlying mesenchyme
Extended into medulla,
form rete ovarii
Primordial germ cells later
incorporated into them forming
oogonium Rete ovarii, primary sex cords
normally disappear At 16
th
week, cortical cords break up
into cell clusters called primordial
follicles (oogonium + follicular cells)

No oogonium form postnatally
Primordial follicles form primary
follicles


Differentiation of Internal Reproductive Tract



Development of Genital Ducts
Initially both ducts are present
Female Male
Paramesonephric duct (lateral)
(Mullerian duct)
Mesonephric duct (medial)


Indifferent Stage
Stage when both pairs of genital ducts are present
Paramesonephric Ducts (Mullerian Duct)
Origin Intermediate mesoderm
Develop from longitudinal invagination of mesodermal epithelium
Located lateral to mesonephric duct
Caudally cross ventral to mesonephric duct, fused to form uterovaginal
primordium/ canal

Development of Genital Ducts, Auxiliary Genital Glands
Female sexual development does not depend on presence of ovaries
Cranial form uterine tubes
Caudal uterovaginal primordium/ canal (form uterus, vagina (superior part))
Endometrial stroma, myometrium are derived from mesenchyme
Fused paramesonephric duct form
y Broad ligaments
y Rectouterine pouch
y Vesicouterine pouch
Adjacent mesenchyme form parametrium

Development of Vagina
Derived from endoderm of urogenital sinus
Fibromuscular wall is derived from mesenchyme
Contact of uterovaginal primordial with urogenital sinus
y Induces formation of paired endodermal outgrowths
y Called sinovaginal bulbs
Sinovaginal bulbs fused, form solid vaginal plate (later canalised)
Cavity of urogenital sinus is separated by lumen of vagina (by hymen)
Both surfaces are lined by endoderm
Hymen rupture at perinatal period




Development of Auxiliary Genital Glands
Bud grow from urethra into mesenchyme, form urethral & paraurethral glands
(of Skene)
Outgrowth from urogenital sinus form greater vestibular glands

Remnants in Females
Mesonephric Paramesonephric
Appendix vesiculosa (cranial end) Vesicular appendages
(cranial end of duct hydatid of
Morgagni)
Epoophoron in broad ligament
between ovary, uterine tube
(correspond to efferent ductules,
duct of epidydimis)
Paroophron
(rudimentary tubules near uterus)
Duct of Gartner
(correspond to ductus deferens,
ejaculatory duct)
Gartners duct cysts
(remnants of mesonephric duct)

Auxiliary Genital Glands
Outgrowths from
y Uretrha paraurethral glands (of Skene)
y UG sinus greater vestibular glands (of Bartholin)
Paramesonephric remnants hydatid of Morgagni
Mesonephric remnants
y Epoophoron
y Paroophoron
y Gartners cyst


Development of External Genitalia (Indifferent Stage)
Distinguishing external genital organs fully differentiate at 12
th
week
At 4
th
week, a genital tubercle develops at cranial end of cloacal membrane
Form on each side of cloacal membrane
y Labioscrotal swellings (lateral)
y Urogenital folds (medial)
Genital tubercle elongates to form phallus

Urorectal septum fuses with cloacal membrane, clocal membrane divided to
y Anal membrane (dorsal)
y Urogenital membrane (ventral)
Urogenital membrane lies at floor of a median cleft (called urogenital groove)
(bounded by urogenital folds)
Urogenital membrane ruptures to form anus, urogenital orifice



Development of External Genitalia
Growth of phallus decreases (become clitoris)
Urogenital folds only fuse posteriorly, form frenulum of labia minora
Unfused part of urogenital folds form labia minora
Labioscrotal folds (mostly remain unfused) to form labia majora
Labioscrotal folds fuse
Posteriorly Anteriorly
Posterior labial commissure Anterior labial commissure
Mons pubis
Phallic part of urogenital sinus form the vestibule of vagina

Formation
Urogenital/ genital folds - Labia minora
Labioscrotal/ genital swellings - Labia majora, Mons pubis
Genital tubercle - Clitoris
Urogenital groove - Vestibule

Descent of Ovary
From lumbar region to true pelvis
Gubernaculum (genital ligament)
(extends from ovary to labia majora)
Round ligament of ovary = ovarian ligament


Differences
6 Weeks 4 Months
Upper, lower gubernaculums in an
embryo in the indifferent stage
Ovarian ligament, suspensory
ligament of ovaries


Urorectal Septum
Cloaca Cloacal Membrane Cloacal Folds
Primitive urogenital
Anorectal canal
Urogenital membrane
Anal membrane
Urogenital folds
Anal folds

Primitive Urogenital Sinus
Urinary bladder
Pelvic part
Phallic part (definitive urogenital sinus)

Congenital Malformation of Female Genital System

Congenital Anomalies of Female Genital System
Female Pseudohermaphrodites Male Pseudohermaphrodites True Hermaphrodites
44 + XX chromosome complement
Most common cause adrenogenital syndrome
Ovaries present
Androgen production
Masculinization
y Clitoral hypertrophy
y Partial fusion of labia majora
y Persistent urogenital sinus
44 + XY chromosome complement
Cause inadequate androgen production
Have testis
Internal, external characteristics
Degree of phallus development
Presence of paramesonephric duct

Extremely rare
Most are reared as female
Physical appearance masculine/ feminine
External genitalia - ambiguous

Conditions Related to Intersexuality
Testicular Feminization Gonadal Dysgenesis (Turners Syndrome) Pure Gonadal Dysgenesis
Appear as normal females
Present of testis XY sex chromosomes
External genitalia Females
y Vagina ends blindly
y Uterus, uterine tubes absent
y Testis in inguinal/ labial regioins
44 autosome XO chromosome
External genitalia normal
Sex characteristics remain infantile
Primordial germ cells present
No/ few true follicles develop
Primordial germ cells migrate into gonadal area
44, XX or 44, XY
Primordial germ cells do not form
Primordial germ cells do not migrate to gonadal area
Ovary/ testis do not develop

At puberty
y Normal development of breasts
y Normal development of female characteristics
No menstruation
Pubic hair scanty



Malformation of Uterus, Vagina
Causes of Malformation
Incomplete fusion of paramesonephric ducts
Incomplete development of one paramesonephric duct
Failure of parts of one/ both paramesonephric ducts to develop
Incomplete canalization of vaginal plate

Uterus Vagina
Uterus didelphys
Uterus entirely double
Failure of fusion of inferior parts of paramesonephric ducts
Arcuate uterus
Fundus is slightly indented in middle
Septate uterus
A septum divides the uterine cavity into 2 parts
Bicornis bicollis
Double uterus
Double cervix
Single vagina
Unicornuate uterus
Unilateral suppression of a paramesonephric duct
Double vagina
Sinovaginal bulbs fail to fuse
Atresia of vagina
Sinovaginal bulbs fail to develop
Vesico-vaginal fistula
Paramesonephric duct ruptures into vesico-urethral part of cloaca
Abnormal communication with urinary bladder
Recto-vaginal fistula
Paramesonephric duct projects into rectal segment of cloaca
Associated with incomplete development of urorectal septum



Immunology of Pregnancy

Pregnancy

3 Syncytiotrophoblast
4 Cytotrophoblast

Transmission of Maternal Antibodies to Fetus
Human neonate does not develop full immune competence
(until several months after birth)(3 months, infant begin to synthesize own IgG)
Depend on maternal antibodies
y In utero (by placental transmission)
Transfer of IgG via placenta begins in 20
th
week of gestation
Most of transfer occurs after 31
st
week of gestation
y From colostrums during breast feeding (IgA)
Only IgG can cross placenta
y Syncytiotrophoblast express receptor for IgG on its cell surface
y Binding, transmission of antibody molecule (IgG)
Expose fetus to deleterious maternal IgG Haemolytic disease of newborn
y Blood group, ABO, Rhesus incompatibility
y Maternal Ab cross placenta destroy fetal erythrocytes
y Leads to haemolytic anaemia in infant
In babies of mothers who smoked
y Impaired production of IL-6, TNF-
y Innate, humoral immune response

Development of Fetal Immune System
Gestation (week) Immune System
4 1
st
blood centers in yolk sac
7-9 Lymphocytes in peripheral blood, thymus
12 Immune recognition of antigen demonstrable
17 Serum IgM can be detected (infection)
30 IgA levels detectable in serum (infection)

Maternal Immune Response during Pregnancy
Enlargement of l/n draining the uterus
Peripheral white blood
Unresponsive to sperm antigen (foreign antigen)
y Ejaculate contains substances that inhibit immune response
y Female genital mucosal immunity tolerance to sperm antigen
Antisperm antibodies (infertility) present in
y 1-10% of normal women
y 75% of women engaged in oral genital intercourse

Mucosal Immunity & Sperm Invasion
Mucosa of female genital tract anatomic, immunologic barrier to host
defences against infection
y Greater no. of intraepithelial, subepithelial lymphocyte
(cervical transitional zone)
Area of enhanced immune activity
(similar to other mucosal surfaces exposed to external environment)
y IgA, IgG in vaginal secretion
Antigen that reaches cervical/ submucosa is thought to be phagocytosed
by APC migrate to l/n, processed, mediated immune response
Except sperm
y Not mediated by immune response
y Uniquely tolerant to sperm antigen
Mamalian fetus inherits 1 parental chromosome each
y 1 paternal
y 1 maternal
As fetus is seen to be foreign to mother, expected to reject embryo
(paternally-inherited antigens provoke immune response against fetus)
But foetuses are not rejected by mother



Mechanisms of Altered Immunity in Pregnancy
Deviation of Immune Response
Humoral Immunity (TH2) Cell-Mediated Immunity (TH1)
Antibody response by recognition of
antigenic surfaces by -cells
T-cells destroy the foreign tissues
Important in transplanted organ
rejection
In pregnancy
Progesterone suppresses TH1 responses

Main immune response
(Humoral immune response TH2)

Expression of TH2 cytokines (IL4, 6, 10)
(beneficial for placental growth, development)
If rejection occur very early in pregnancy, theres no time for +ve pregnancy
(had not achieved a pregnancy at all infertility)
If occur later, recurrent abortion
Trophoblast
Physical barrier
y Placenta can filter harmful antibodies from reaching embryo
Weak antigenicity
Presence of sialic acid, fibrinogen on trophoblast
y Mask antigenic sites of trophoblast
Local production of progesterone, other immunosuppressive hormones
Expression of HLA molecules
Syncythiotrophoblast does not express surface class 1 HLA-A,B
Cytotrophoblast only express HLA-G
y Does not stimulate cytotoxic activity
y Inhibit NK cell activity
Expression of complement regulatory proteins
Complement cascade of 20 plasma proteins, cleavage products create MAC
Classical pathway, alternative pathway
Ability of MAC to lyseforeign cells
(enhanced by action of cleavage products that increase)
y Vascular permeability
y Vasodilatation
y Leukocyte chemotaxis
Trophoblast express 3 proteins that down-regulate complement system
(complement regulatory proteins)
y Membrane co-factor protein (MCP)/ (CD46)
y Accelerating factor (DAF)/ (CD55)
y Membrane attack inhibitor (CD59)
In placenta, complement system is highly down-regulated by DAF, MCP, CD59
Complement regulatory proteins
y Provides protection from maternal complement mediated damage
y Minimize tissue damage
Antipaternal leucocyte antibodies (APLA)
APLA Ab that mask paternal human leukocyte antigen (HLA)
When pregnant, uterine lymphocytes produce APLA (against fathers HLA)
Protect fetus from maternal killer cells (capable to reject fetus)
FAS
Fas Ligand (FASL) expressed in trophoblast tissue
Apoptosis is initiated in maternal immune lymphocytes
(when FAS contacts with FASL on placental tissue)
Maternal lymphocytes suicide (once FAS/ FASL interaction occurs)
Immune response
Fetal rejection
Indolamine 2,3-dioxygenase (IDO)
Enzyme produced by macrophages, catabolises tryptophan
Prevent fetal rejection inhibit T cell proliferation (consuming tryptophan)
IDO catabolises tryptophan

No tryptophan

No T cell proliferation

No immune response

No fetal rejection


UPT (Urine Pregnancy Test)
Agglutination
Principle
Latex agglutination test
y Early detection of hCG in urine
(latex beads coated with monoclonal Ab to hCG)
y If hCG present in urine,
it will react immunologically with anti hCG-latex bead
Results
+ve False +ve
Normal pregnancy
Hydatidiform mole
Chorioepithelioma of uterus, testis
Proteinuria
Hematuria
Bacterial infection
Methadone



Physiological Changes During Pregnancy

Metabolic Changes
Placenta secretes hPL (human placental lactogen)
(also known as hCS (human chorionic somatomammotropin))
hPL
Promotes growth of fetus
Exerts a maternal glucose-sparing effect
hCT (Human chorionic thyrotropin)
Maternal metabolism
Parathyroid hormone
+ve calcium balance

Physiological Changes
GIT
Morning sickness (due to estrogen, progesterone)
Urinary system
Urine production (handle additional fetal wastes)
Respiratory system
Edematous
Nasal congestion
Dyspnea (may develop late in pregnancy)
CVS
CO ( Stroke volume)
Apex beat moved laterally
Cardiac capacity (70-80mL)(due to volume/ hypertrophy of cardiac ms.)
BP
Venous pressure
y Pressure of pregnant uterus on femoral vein, IVC
Impede blood flow from legs
y Venous pressure
Force fluid out cause edema
y Distensibility of veins
y Lateral recumbent position (relief pressure on femoral vein, IVC)
Hematological system
Total plasma volume
Blood volume
y Blood flow to uterus, kidneys
y Serum albumin - Oncotic pressure general edema (lower limbs)
RBC
y Red cell volume (but lag behind plasma volume)
Hematocrit, [Hb]
Physiological anaemia of pregnancy
y Stimulate erythropoiesis progesterone, hPL, PRL
Iron requirement (maternal iron deficiency)
Total WBC
Clotting factors
Pulmonary system
Engorgement of nasopharynx, larynx, trachea, bronchi (capillary dilatations)
Voice change, breathing via nose difficult, CXR - vascular markings in lungs
Tidal volume
FRC (functional residual capacity)
pCO2 (secondary to alveolar hyperventilation)
Bicarbonate (metabolic compensation)
pO2 while upright (may fall when supine)
Pulmonary circulation
y Pulmonary vascular resistance
y Pulmonary blood flow
y Pulmonary blood volume
y O2 consumption (due to metabolic demands of fetus, uterus, placenta)

Dead volumes
Tidal volumes
Total lung capacity
Functional residual capacity, residual volume, respiratory reserve volume



Physiological Changes (cont.)
Urinary system
Renal dilatation
y Length, Weight of kidneys
y Dilated Renal pelvis, Ureters (urinary stasis - infection)
Hydronephrosis, Hydroureter
y Progesterone (hypotonia of smooth ms. in ureter)
y Enlarged ovarian vein complex (dilatation)
y Dextrorotation of uterus
y Hyperplasia of smooth ms.
Renal plasma flow rate
GFR (but volume of urine passed is not increased)
Glucosuria ( GFR impaired tubular reabsorption capacity to filter glucose)
Proteinuria
Renin
Bladder
y Urinary frequency (pressure from uterus)
y Bladder vascularity
y Muscle tone
y Bladder capacity
GIT system
GIT motility (due to progesterone) (constipation)
Gastric reflux
Gums hypertrophy, Vitamin C deficiency, Bleeding gums
ALP (liver)
Reproductive
Goodells sign softening of cervix (on pelvic exam)
Chadwicks sign purple hue of vagina, cervix
Hegars sign compressibility, softening of isthmus
Uterine hypertrophy (of myocytes)
y Venous return
y CO
y TPR (to minimize fall in BP)
Endocrine system
Anti-insulin environment, aided by
y Placental lactogen
Similar to GH
Lipolysis, FFA
Tissue resistance to insulin
y Unbound cortisol
y Estrogen, progesterone exert anti-insulin effects
Thyroid
y TBG
y Total T3, T4
y hCG stimulates thyroid ( TSH)
y Iodine deficiency state ( renal clearance)

Metabolism
Weight
y Uterus and its contents
y Breast tissue, blood, water volume
y Average weight 12.5kg
CVS
Estrogen - RAA
Stimulate erythropoiesis progesterone, hPL, PRL
CVS changes due to a-v shunt through placenta (late pregnancy)
Pulmonary
Intraabdominal pressure (force diaphragm upward)
BMR of growing fetus - maternal O2 consumption, CO2 production
Progesterone acts on CNS to set-point for regulation of respiration by CO2
( Ventilation)
Renal
RAA (due to BP)
Estrogen stimulates liver synthesis of angiotensinogen
Estrogen, progesterone - ACE
DOC (placental deoxycorticosterone)
y Mineralocorticoids
y Aldosterone
CNS
Sensitivity to PaCO2
Volume of epidural space
Pressure of epidural space
CSF volume
CSF pressure
Sensitivity to local anaesthetics
Local anaesthetic dose

Physiology of Puberty

Definition
Physiological transition from childhood to reproductive maturity
Developmental phase characterised by
y Appearance of secondary sexual characteristics
y Adolescent growth spurt
y Attainment of fertility
Pubertal development takes place over a period of 4 years
Tanner staging of puberty (sexual maturity rating SMR)
Female Male
Breast maturation
Pubic hair growth
Genital development
Pubic hair growth
Physical signs of puberty Marshall & Tanner
(Fairly regular sequence of events between ages of 10-16 y/o in girls)
Growth spurt
Breast growth (thelarche)
Pubic hair (pubarche)
Axillary hair (adrenarche)
Menstruation (menarche)

Growth Spurt
IGF-1, GH
Peak serum IGF-1 reached about 1 year after peak growth velocity
(remain above normal adult lvl up to 4 years thereafter)
Sex steroids, either
y Indirectly through GH
y Directly stimulate IGF-1 production in cartilage
Estrogen
y Stimulate maturation of chondrocytes
y Stimulate maturation of osteoblasts (maturation of bone age)
y Lead to epiphyseal fusion


Pubertal Growth Spurt
Girls Boys
Begins in early pubertal
Completed by menarche
Occurs toward end of puberty
(2 years older than in girls)
Average difference in height (male, female) = 10 cm
(2 additional years of prepubertal growth)


Changes in Body Composition
Prepubertal (boys, girls) start with equal
y Lean body mass
y Skeletal mass
y Body fat
Matured
Men Women
Lead body mass
Skeletal mass
Muscle mass
Body fat



Male Changes
Testes size (> 2.5cm) (equivalent to testicular volume > 4ml)
Due to seminiferous tubular development (FSH stimulation)
Pubic hair development (due to adrenal, testicular androgens)
Appearance of spermatozoa in early morning urine (spermache) at 13.4 y/o

Stages of Pubic Hairs Development (Boys)
Stage Description
1 Preadolescent, no pubic hair
2 Sparse, long pubic hair, chiefly at base of penis
3 Hair darker, coarser. Hair spread sparsely over pubic junction
4 Hair adult-type, but area covered is less than adult
5 Adult hair texture, quantity
Hair is distributed as inverse triangle of feminine pattern
Spread occurred to medial surface of thighs


Stages of Genital Development (Boys)
Stage Description
1 Preadolescent
2 Scrotum, testes enlarge
Change in scrotal skin texture
No enlargement of penis
3 Growth of penis in length
Further growth of testes, scrotum
4 Growth of penis in legth, girth
Further enlargement of testes, scrotum
Darkening of scrotal skin
5 Adult-sized genitalia


Female Changes
Growth velocity
Breast development
y Stimulated by ovarian estrogen
y Size, shape determined by genetic, nutritional factors
Estrogen actions
y Enlargement of labia minora, majora
y Dulling of vaginal mucosa (from prepubertal reddish hue)
y Production of clear/ slight whitish vaginal secretion (prior to menarche)
y Change in uterine size, shape
y Change in ovarian size

Stages of Breast Development (Girls)
Stage Description
1 Preadolescent (only papilla elevated)
2 Breast bud, papilla elevated
Small breast mound present
Areola diameter is enlarged
3 Enlargement of breast mound
Palpable glandular tissue
No separation of their contours
4 Areola, papilla project to form 2 mould (above breast level)
5 Adult breast
Only papilla projects


Stages of Pubic Hair Development (Girls)
Stage Description
1 Preadolescent (no pubic hair)
2 Slight growth of fine pubic hair
3 Hair darker, coiled, denser
4 Adult-type hair (area covered is less than adult area)
5 Adult-type hair (with triangular-shaped distribution)


Pubertal Stage (Tanner)



Endocrine Changes


Hormones & Puberty
Hypothalamus stimulates pituitary gland
y GH causes growth spurt
y Ovaries, testes release gonadotrophins (sex hormones)
Male testosterone
Female estrogen, progesterone


Hypothalamus-Pituitary-Gonadal Axis
Fetal (1-2 years) Prepubertal Puberty
GnRH pulse
generator
Active
Frequency
Amplitude
Reactivating
LH, FSH
Sex Steroids - Girls E2
Sex Steroids - Boys E2 (until birth)
T


Ovulation, Menarche
Last stage of HPG development onset of +ve feedback (ovulation, menarche)
Estrogen (after mid puberty) stimulate, suppress gonadotropin secretion
GnRH

Stimulate ovary to produce estrogen

LH (mid cycle)

Ovulation
90% of menstrual cycles anovulatory in 1
st
year after menarche
4-5 years after menarche, <20% anovulatory cycles

Menstrual Cycle, Uterine Endometrial Responses



Adrenarche
Stage of maturation of adrenal cortex
Adrenal androgens (dehydroepiandrosterone, DHEA sulphate)
Starts around
y Girls 6-7 y/o
y Boys 7-8 y/o
y Continued rise in secretion (of adrenal androgens) until late puberty
Functions
y Promote pubic hair growth
y Promote axillary hair growth
Age at adrenarche does not significantly influence age at gonadarche

Mechanisms of Puberty
Gonadostat Hypothesis
Hypothalamic Maturation
Hypothesis
-ve feedback regulation of
gonadotropins operate at
threshold
(sensitive to low steroid levels)
Maturation of hypothalamus
GnRH is driving force for puberty
At puberty, threshold
(less sensitive)
LH, FSH levels
Puberty involves a change in set point
(but not driving force for puberty)

Timing of Puberty
Genetic/ Environment
Genetic Environment
50% variation of timing of puberty
Association mother, daughters
Body fat (weight)
Delay puberty vegetarian diet
( protein, plant fiber)
Physical activity
Exercise (delay puberty)
Amplified by body fat mass
Physical illness
Chronic illness (delay puberty)
Environmental chemical/ drugs
Pharmaceutical sex steroids (early puberty)
Polychlorinated biphenyls (PCBs) (bind, trigger ER)
Stress, Social Factors
Stress (early puberty)
Wartime (nutrition) (delay puberty)

Abnormalities of Puberty
Delayed Puberty Precocious Puberty
Girl 13 y/o
Boy 14 y/o
No signs of pubertal development (falls > 2.5SD below mean)
Appearance of secondary sexual development
(>2.5 SD below mean at onset of puberty)
y Girls <6-7 y/o
y Boys < 9 y/o
Sex
Boys Girls
Genital stage (Tanner) 1 after 13.7 yrs
(childlike phallus, testicular V < 1.5ml)
Breast stage (Tanner) 1 after 13.4 yrs
(no glandular tissue)
Pubic hair stage 1 (>14.1 yrs)
Failure to menstruate before 16 y/o
> 5 yrs from initiation to completion
of genital growth
> 5 yrs from initiation of breast
growth to menarche
Sexual maturity ratings lag in
expected durations
(genital, pubic hair stages)
Sexual maturity ratings lag in
expected durations
(breast, pubic hair stages)

Types
True Precocious Puberty Pseudoprecocious Puberty
Sex glands (ovaries, testes) mature Outward appearance becomes more
adult Childs outward appearance becomes
more adult Sex glands remain immature
Pubic hair grows
Childs body shape changes
2-5X more common in girls
(than boys)

Causes
Physiological hypogonadotrophic hypogonadism
(constitutional delay of growth, puberty)
Malabsorption celiac/ inflammatory bowel disease
Underweight dieting, anorexia nervosa, over-exercise
Chronic illness asthma, malignancy, -thallasaemia major, cranial trauma/
tumor/ irradiation
Congenital deficiency (rare)
y Kallmanns syndrome
y Prader-Willi syndrome
Hypergonadotrophic hypogonadism (ovaries do not respond)
y Turner syndrome (XO)
y Ovarian damage irradiation, chemotherapy
y Autoimmune addisons, vitiligo, hypothyroid
y Rare CAH - 17hydroxylase deficiency
(21 hydroxylase causes virilisation/ salt wasting at birth)
Gonadotrophin
Gonadotrophin-dependent
(true/ central)
Gonadotrophin-independent
Idiopathic
Family history
Overweight/ obese
74% of girls
Intra-cranial lesions
y Tumours
y Hydrocephalus
y CNS malformations
y Irradiation
y Trauma
Gonadotrophin secreting tumours
CAH
Sex steroid secreting tumours
y Adrenal, ovarian
y Peutz-Jeghers syndrome
McCune-Albright syndrome
y Irregular areas of skin
pigmentation
y Polyostotic fibrous dysplasia
y Ovarian functional cysts
(due to autonomous ovarian
activation)
(absent nocturnal pulses)
Gonadotropin secreting ovarian/
adrenal tumours
Estrogen ingestion

Classification
Hypogonadotropic hypogonadism Hypergonadotropic hypogonadism
CNS disorders tumours
Isolated gonadotropin deficiency
Kallmans syndrome
Gonadotropin deficiency
(with normal sense of smell)
Multiple pituitary hormonal def.

Prader-Willi syndrome
Laurence-Moon
Bardet-biedl syndrome
Chronic disease
Weight
Anorexia nervosa
Physical activity
Hypothyroidism
Male
Klinefelter syndrome
Other primary testicular failure
Cryptorchism
Female
Turner syndrome
Other primary ovarian failure

Pseudo-Turner syndrome
Noonan syndrome
XX, XY gonadal dysgenesis

Classifcation
Central (complete/ true) precocious puberty
y Constitutional
y Idiopathic
y CNS disorders
y Following androgen exposure
Incomplete precocious puberty
y Male gonadotrphin secreting tumours, excessive androgen production,
premature leydig cell maturation
y Female ovarian cysts, estrogen secreting neoplasm
y Both sexes severe hypothyroidism, McCune-Albright syndrome
Sexual precocity due to gonadotrphin/ sex steroid exposure
Variation in pubertal development
y Premature thelarche
y Premature menarche
y Premature pubarche
y Adolescent gynaecomastia


Drugs & Pregnancy

Definition
Teratogens
Drug/ substances that cause physical abnormalities in offspring of pregnant
mothers given that substance
Teratogenic risk
Dysmorphogenesis (major structural abnormalities)
When organs forming, drugs cause big structural abnormalities

Substances
Drugs (thalidomide phocomelia)
Alcohol
y Abortion
y Fetal death
y Physical & mental development affected
y Birth weight
y Alcohol fetal syndrome (CNS, facial growth development affected)
Caffeine
Smoking
y Birth weight
y Growth effect intellectual, behavioural
y Pregnancy complications (mother)

FDA Pregnancy Risk Classification
Category A Category B Category C Category D Category X
Fail to show risk to fetus
Possibility appears remote

Have not demonstrated fetal
risk (animal study)
No confirmed in controlled
studies
Revealed adverse effects on
fetus (teratogenic/
embryocidal effects)
Given if benefit > risk to fetus
+ve evidence of fetal risk
Given if benefit > risk
(life threatening situation)

Fetal abnormalities
Evidence of fetal risk
Contraindicated in pregnancy

Folic acid Chlorphennamine
Ampicillin
Erythromycin
Methyldopa
Ceftriaxone
Amoxicillin
Chloramphenicol
Gentamicin
Aspirin
Prednisolone
Co-trimoxazole
Losartan
Omeprazole
ACE Inhibitor
Carbamazepine
Chlorpropamide
Iodine
Diazepam
Valproic acid
Methotrexate
Phenytoin
Other aminoglycosides
Aspirin (full dose 3
rd
trimester)
Prednisolone (3
rd
trimester)
Co-trimoxazole (near term)
Losartan (2
nd
, 3
rd
trimester)
Aminopterine
Diethylstilbestrol
Danazol
Estrogens
Etretinate
Isotretinoin
Warfarin
Vaccines (MMR, varicella)
Atorvastatin

Factors Affecting Drug Effects on Fetus
Molecular size
Molecular size (< 600) pass placenta easily
Molecular size (> 15000) pass placenta with difficulty
y Heparin
y Insulin
y Thyroxin
Lipid solubility
Lipophilic drugs pass placenta easily (pass cell membrane easily)
(eg. Thiopental)
Protein binding
Causes transfer to be slow
Cross placenta easily
Molecular size
Non-protein bound
Non-ionized
Liphophilic

Pharmacokinetic
Most drugs crosses placenta, expose fetus to its effects
Usually fetal blood concentration 50-100% of maternal concentration
Drug eliminated by mother (on behalf of fetus)
Time of fetus exposure to drug
1
st
3 weeks cause spontaneous abortion
3
rd
10
th
week gross malformations
11
th
week birth smaller malformations, growth retardation, withdrawal syn.


Teratogenic Drugs
Warfarin (anticoagulant)
Crosses placenta (not used in pregnancy)
Cause congenital malformation (given in early pregnancy)
y CNS
y Ophthalmic abnormalities
y IUGR
Causes placental, fetal bleeding (given in late pregnancy)
Fetal warfarin syndrome
Heparin (alternative to warfarin to be given)( molecule)
Thalidomide
Phocomelia
Retinoids
Vitamin A analogue (etretinate, isotretinoin)
Used for skin conditions serious acne, psoriasis
Congenital abnormalities CNS, craniofacial, heart
Cytotoxics (1
st
trimester)
Congenital malformations
Spontaneous abortion
Fetal death
Chromosomal abnormalities
Hormones (estrogen, androgen)
Stilboestrol (synthetic estrogen)
y Abortion
y Vaginal ca (teens, 20s)
Genitourinary, other abnormalities (eg. CVS, skeletal)
Tetracycline
Tooth (yellow) discoloration of teeth
Enamel hypoplasia
Impair fetal bone growth (tetracycline concentrated at teeth, bones)
Anti-Epileptics (sodium valproate, pheyntoin)
Congenital malformations
y Craniofacial abnormalities
y Congenital heart problems
y Neural tube defect
Fetal death
IUGR
Valproic acid neural tube defect, skeletal system, cranial abnormalities
Phenytoin (Dilantin) congenital abnormalities (fetal hydantoin syndrome)
Carbamazepine
Phenobarbitone withdrawal syndrome

Drugs Producing Fetal Abnormalities
Oral hypoglycemics/ Oral diabetic drugs
Can pass placenta
Prolonged newborn hypoglycaemia
Stimulate fetal insulin secretion
Insulin molecule, cannot pass placenta
Opiates
Withdrawal symptoms

Drugs Causing Adverse Effects if Near Delivery
Opiates, Barbiturates (CNS depressants)
Withdrawal syndrome
CNS depression
Addicted baby
Premature delivery
IUGR
Perinatal mortality
Chloramphenicol
Grey Baby Syndrome (CVS collapse)
Aspirin
Excess bleeding in mother during delivery
Bleeding in neonate
Premature closure patent ductus arteriosus
Sulphonamide
Kernicterus (remove bilirubin from plasma protein)


Supplements During Pregnancy
Iron
Meat, liver, fish
Ferrous sulphate, ferrous fumarate
Side effect constipation, dark stools
Folic acid, Vitamin B12
Meat, green vegetables
For blood forming cells, proper growth of other cell types
Neural tube defect in fetus/ newborn
Calcium
Fetal bone, teeth formation

Infections During Puerperium

Definition (Puerperal Sepsis)
ICD-10
Temperature > 38C (100.4F)
Maintained over 24h
Recurring during end of 1
st
to end of 10
th
day after childbirth/ abortion
WHO
Infection of genital tract
Any time between onset of rupture of membranes/ labor
To 42
nd
day postpartum
Fever and
y Pelvic pain
y Abnormal vaginal discharge
y Abnormal odor of discharge
y Delay in rate of size of uterus

Causes of Puerperal Infections
Endometritis (endomyometritis, endomyoparametritis)
Wound infection
Mastitis
Urinary tract infection
Septic thrombophlebitis

Predisposing Factors
Home births, unhygienic conditions
Socioeconomic status
Poor nutrition
Primiparity
Anaemia
Prolonged rupture of membranes
Prolonged labour
Multiple vaginal examinations in labor (>5)
Cesarean section
Obstetrical manoeuvres
Operative, traumatic delivery
Retention of placental fragments within uterus
Postpartum haemorrhage
Cesarean section
Postpartum endometritis (greatest risk 20-30x relative risk than vaginal)
Due to
y Tissue necrosis
y Postoperative serosanguinous fluid collection
y Bacteria in
Surgically traumatized tissue
Myometrial blood vessels
Peritoneal cavity



Microbiology
Aerobes Anaerobes Miscellaneous
Gram +ve
-hemolytic streptococcus
Staphylococcus epidermis
Staphylococcus aureus
Gram ve
Escherichia coli
Enterobacteriaceae
y Klebsiella pneumonia
y Enterobacter
y Citrobacter
Pseudomonas aeruginosa
Proteus mirabilis
Haemophilus influenza
Gram variable
Gardenerella vaginalis
Peptococcus sp.
Peptostreptococcus sp.
Bacteroides
y Fragilis
y Bivis
y Disiens
Clostridium ramosum
(rarely Cl. perfringens)
Fusobacterium
Chlamydia trachomatis
Mycoplasma hominis
Uroplasma urealyticum
Majority of cases of endometritis
Polymicrobial aerobic, anaerobic organisms

Signs & Symptoms
Fever, chills
Flank pain, dysuria, frequency of urinary tract infections
Erythema, drainage from surgical incision/ episiotomy site
Respiratory symptoms
y Cough
y Pleuritic chest pain
y Dyspnea
Abdominal pain
Foul-smelling lochia
Breast engorgement (mastitis)

Sites of Puerperal Infection Differential Diagnosis
Sites Differential Diagnosis of Pyrexia
Endometrium Endometritis
Parametritis
Pelvis Pelvic abscess
Lungs Respiratory infections
Urinary tract Urinary tract infections
Wound Cesarean section
Episiotomy
Vaginal/ cervical thrombophlebitis
Veins Septic thrombophlebitis
Breasts Mastitis
Other Venous catheters
Endocarditis
Systemic infections (hepatitis)

Specific Infections

Wound Infection
Cesarean section
Factors determining the rate Risk Factors
Length of labour
Duration of internal monitoring
No. of vaginal examinations
Antibiotic prophylaxis use
Chorioamnionitis
Obesity
Prolonged surgical time
Blood loss (at surgery)
Examination of wound
Erythema
Swelling
Tenderness
Discharge

Pelvic Abscess
Persistent spiking fever (despite antibiotic coverage)
US/ CT fluid, gas collections (shaggy walls, fluid in cul-de-sac)
Treatment surgical drainage

Episiotomy Infection
Confined to skin, subcutaneous tissue (limited by Campers fascia)
Perineal pain, hip pain, erythema, swelling
Pelvic examination hematomas, abscess
Treatment
Sitz bath (if no abscess/ extension)
Exploration of episiotomy
Drainage, debridgement

Thrombophlebitis
Cesarean section (more common than vaginal delivery)
Hypercoagulable state (ascent of infection)
(spread from myometrium to pelvic, ovarian veins)
Injury to intima of pelvic vein, caused by
y Uterine infection
y Bacteremia
y Endotoxins
y Trauma of delivery
y Surgery
Virchows triad hypercoagulable state, blood flow, venous stasis
Signs & symptoms
y Flank, lower abdominal pain non-colicky, constant
(rope/ sausage-shape mass)
y Pain variable intensity, radiate to groin/ upper abdomen
Paralytic ileus may occur
y Pulmonary embolus
Diagnosis
y Poor antibiotic response
y Mass palpable on pelvic examination
y CT/ MRI of pelvis
y +ve response to trial of anticoagulation therapy (heparin)
Treatment heparin, antibiotics (broad-spectrum)

Mastitis
Causes
Staphylococcus aureus
Streptococci Group A, B
Haemophilus
Clinical Findings
Fever
Breast tenderness (localized)
Erythema
Gram stain
Polymorphonuclear cells
Causative organism
Differentiate from late engorgement (caused by milk stasis)
Cause inflammation of breast
Not associated with fever, cracked nipples
Does not require antibiotic therapy
Treatment
Ice-packs
Analgesia
Breast support
Penicillinase-resistant antibiotic
Treatment (breast abscess)
Incision
Drainage
Continue breast feeding (unless abscess formed)



Urinary Tract Infection (UTI)
Signs & symptoms
Urinary frequency
Dysuria
Fever
Diagnosis
Clinical findings
Urine specimen > 10
5
colony forming U/mL
GIT organisms
May experience reinfection even with appropriate treatment (rectal reservoir)
Causes
Most common (gram ve rods) Less Common
Escherichia coli
Proteus mirabilis
Klebsiella pneumonia
Enterococci
Gardnerella vaginalis
Ureaplasma ureolyticum
Group B Streptococcus
Staphylococcus saprophyticus

Urinary stasis, Ureterovesical reflux
Bladder volume
Bladder tone
Ureteral tone
Urinary progestins, estrogens
Ability of lower urinary tract to resist invading bacteria
Bacteriuria in postpartum
Asymptomatic
Urethral catheterization (risk factor)
Treatment antibiotic (3-day course) (in uncomplicated cases)
Complications
Acute pyelonephritis (during puerperium)
Maternal sepsis
Diagnosis
Bacteriuria
Fever, chills, nausea, vomiting, flank pain
Frequency, dysuria

Maternal Mortality

Definition
Death of women
y While pregnant
y Within 42d of termination of pregnancy
Irrespective of duration, site of pregnancy
Not from accidental, incidental causes
Death
Direct Death Indirect Death
Obstetrics complications pregnancy
Labour, puerperium
Interventions
Omissions
Incorrect treatment
Pre-existing disease
Condition arising during pregnancy
Aggravated by physiological
changes in pregnancy


Causes of Maternal Death
Associated medical condition (respiratory, heart, HIV)
Postpartum haemorrhage
Hypertensive disorder in pregnancy (chronic, pre-eclampsia, gestational HPT)
Obstetric embolism (amniotic fluid, thromboembolism)
Obstetric trauma
Puerperal sepsis
Antepartum haemorrhage (placenta praevia, placental abrution, uterine rupt.)
Abortion (septicaemia from miscarriage, shock due to miscarriage)
Ectopic pregnancy
Associated with anaesthesia

Perinatal Mortality

Definition
Death occurring in perinatal period
y Period after 22 weeks
y Weighing 500g
y Crown-heel length 25cm
Death occurring between birth and 1
st
7 days of life
Live Birth
Complete expulsion, extraction from its mother of a baby
Irrespective of gestational age
Shows signs of life
y Breathing
y Beating of the heart
y Pulsation of umbilical cord
y Definite movement of voluntary muscles
Still Birth
Birth of a baby, from 24 completed weeks of gestation
No signs of life after birth
Macerated Stillbirth
Death of fetus 500g (or of gestational age of 22 weeks if weight unknown)
Present of peeling of skin
Fresh Stillbirth
Death of fetus 500g (or of gestational age of 22 weeks if weight unknown)
Absent of peeling of skin
Neonatal Death
Death in a live birth, weight 500g
Early Neonatal Death Late Neonatal Death
< 7 completed days of each 7-27 completed days of each




Causes of Perinatal Mortality
Lethal congenital malformation (LCM)
y Neural tube defect
y Cyanotic heart disease
y Hydrops fetalis
y Congenital malformation
Asphyxial condition (fresh, stillbirth, neonatal death)
y Meconium aspiration syndrome
y Birth trauma
Immaturity (neonatal only)
Infection (neonatal only)

Perinatal Death Risk Factors
Height short mothers
Parity - 4
th
pregnancy
Age - <20y/o, >30y/o pregnant ladies
Socio-economic conditions underprivileged classes

Preventing Perinatal Death
Smoking, alcohol
Vaccination rubella
Immunize all primaparae with anti-D immunoglobulin
Knowledge

Anatomy of Pelvis

Pelvis
False Pelvis True Pelvis
Pelvis major (greater pelvis) Pelvis minor (lesser pelvis)
Boundaries
Anterior Abdominal wall
Posterolateral Iliac fossae
Posterior L5-S1 vertebrae
Contents
Abdominal viscera
y Ileum
y Sigmoid colon
Contents
Pelvic viscera
y Urinary bladder
y erminal parts of ureters
y Reproductive organs
y Rectum


Apertures of True Pelvis
Pelvic Inlet Pelvic Outlet
Bounded by
Superior margin of pubic symphysis
Posterior border of pubic crest
Iliopectineal line
Anterior border of ala of sacrum
Sacral promontory
Bounded by
Inferior margin of pubic symphysis
Inferior rami of pubis, ischial tuberosity
Sacrotuberous ligaments
Tip of coccyx
Measurement
AP 12cm
Transverse 13cm
Measurement
AP 12.5cm
Transverse 11cm



Pelvic Floor


Levator Ani Muscle
Contraction of levator ani muscles raise entire pelvic floor
Functions
Control of urination, defecation (relaxation allow urinary, defecation)
Support for viscera (eg. uterus, bladder)
Direct fetal head toward birth canal at parturition



Differences - Male, Female Pelvis


Male

Female

Normal Pelvic Variants


Pelvic Changes during Pregnancy
During late pregnancy, pelvic joints, ligaments relax
Pelvic movements
Relaxation caused by sex hormones, relaxin
Pelvic diameter during childbirth

Fetal Skull

Anatomy


Facial Skeleton of Term Fetus
Facial skeleton is relatively small
Smallness of face due to
y Rudimental development of maxillae, mandible, paranasal sinuses
y Absence of erupted teeth
y Small size of nasal cavities
Nose lies entirely between orbits
Orbits appears relatively larger

Characteristics of Fetal Skull
Mastoid process is absent
Stylomastoid foramen is exposed on lateral surface of skull
Styloid process has not fused with temporal bone
Glabella, superciliary arches are not developed
Cranial base is relatively short, narrow
Paranasal sinuses are rudimentary, absent
External acoustic meatus is short, straight, cartilaginous
Ossification is incomplete



Sutures




Fontanelles

Anterior Fontanelle Posterior Fontanelle
Diamond, rhomboid in shape Triangular in shape

Drugs Affect|ng Uter|ne Contract|on Lactat|on

Uter|ne St|mu|ants ( Uter|ne Contract|||ty)
Cxytoc|n (IV IM) Lrgometr|ne (Cra| IV IM) rostag|and|ns (asser|nes 1ab|ets Ie||y)
SecreLed ln posLerlor plLulLary
ke|ease by st|mu|| (CxyLocln AuP)
ColLus
arLurlLlon
Suckllng
PyperLonlc sallne lnfuslon
WaLer deprlvaLlon
Pemorrhage
aln apprehenslon aL dlfferenL proporLlon
(depend on naLure of sLlmull)

8eleased durlng labour
(noL obllgaLory for lnlLlaLlng parLurlLlon)
lorce of uLerlne conLracLlons
lrequency of uLerlne conLracLlons
8elaxaLlon ln beLween conLracLlons
8asal Lone ( uoses)
Lower segmenL of uLerus noL conLracLed
Cnly resLrlcLed Lo
O lundus of uLerus
O 8ody of uLerus
Lffects on Uterus
uopamlne adrenerglc recepLors agonlsLs
lorce frequency duraLlon of uLerlne conLracLlon
Dose
Moderate n|gh
ConLracLlon superlmpose
on a Lonlc conLracLlon
SusLalned Lonlc
conLracLlon
Cravld uLerus more senslLlve
SLlmulaLe lower segmenL conLracLlon as well
CL1 CL2 CL3 acL on uLerus
SenslLlvlLy wlLh progresslon of pregnancy

Cs produced by feLus lnlLlaLe labour
Cl2 presenL ln maLernal blood aL Lerm
Cs presenL ln amounL ln semen
Cs sofLen cervlx
nSAlus delay lnlLlaLlon slow progresslon of labour
MCA
AcLs on CproLeln couple oxyLocln recepLor
uepolarlzaLlon of muscle flbre lnflux of Ca2+
uLerlne muscle conLracLlons

LsLrogen senslLlze uLerus Lo oxyLocln
8elaLlvely noL senslLlve Lo oxyLocln
(nonpregnanL uLerus/ earlypregnancy uLerus)
System|c Lffects
CVS kena|
ulrecL vasodllaLaLlon
8
8eflex Lachycardla
llushlng
AuP llke acLlon ( dose)
urlne ouLpuL
ulmonary edema ( lv)

System|c Lffects
CvS weaker vasoconsLrlcLor
CnS acLs on recepLors (no effecL aL LherapeuLlc dose)
Cl1 dose perlsLalsls movemenL of guL
System|c Lffects (IV Cra|)
SysLemlc adverse effecLs
CvS
8esplraLory
Cl1
8enal
Induct|on of Labour
Ind|cat|on Contra|nd|cat|ons
osLLerm
1oxaemla of pregnancy
uM
Cu
lacenLa praevla
leLal dlsLress
revlous uLerlne scar
Mode slow lv lnfuslon (dose ad[usLed severlLy)
8enef|ts Adverse Lffects
ShorL 11/2 Strong uter|ne contract
MaLernal feLal sofL Llssue
ln[ury
uLerlne rupLure
leLal asphyxla (deaLh)
n2C |ntox|cat|on
(ADn ||ke act|on)
1oxaemla of pregnancy
8enal lmpalrmenL
ulmonary edema
Cardlac fallure
ConLrollable lnLenslLy
AcLlon can be LermlnaLed
8elaxaLlon bLw conLracLlon
(malnLaln feLal C2)
Lower uLerlne segmenL noL
conLracLed (feLal descenL
noL compromlsed)

C||n|ca| Uses
revenL LreaL P
SynLomeLrlne (ergomeLrlne + oxyLocln)
osL LSCS lnsLrumenLal dellverles (prevenL uLerlne aLony)
Lncourage normal lnvoluLlon
O MulLlpara women
O Women wlLh slow lnvoluLlon
C||n|ca| Uses
AborLlon
O 1
sL
LrlmesLer aborLlon lnLravaglnal CL2 CL1
Pelps sofLen cervlx
Mlnlmlze Lrauma durlng dllaLaLlon of cervlx
O lrequenLly used ln
Mlssed aborLlon
Molar pregnancy
2
nd
LrlmesLer aborLlon
SofLen cervlx lmprove senslLlvlLy of uLerus Lo oxyLocln
O CompllcaLlon lncompleLe aborLlon
lnducLlon/ augmenLaLlon of labour
Cervlcal prlmlng
osL parLum haemorrhage

Adverse Lffects
nausea vomlLlng 8 chesL paln dlzzlness headache
Mllk producLlon ( dose)
Should avold ln
O vascular dlseases hyperLenslon Loxaemla
O resenL of sepsls gangrene
O Llver kldney dlseases
ConLralndlcaLed ln pregnancy
Uter|ne Inert|a
lndlcaLlon
O When uLerlne conLracLlon ls feeble ( sLrengLh)
O Labour ls noL progresslng
CxyLocln uLerlne conLracLlon

ost artum naemorrhage Cesarean Sect|on
LrgomeLrlne (frequenLly used)
CxyLocln (lv/ lM) can be used
O 8apld onseL of acLlon
O aLlenL wlLh hyperLenslon (ergomeLrlne conLralndlc)
uose causes
O 8asal Lone
O uuraLlon of uLerlne conLracLlon
O SusLalned Lonlc conLracLlon
Adverse effecLs P2C reLenLlon
Cxytoc|n Cha||enge 1est (8lsky LesL)
lndlcaLlon deLermlne uLeroplacenLal adequacy

1oco|yt|cs
2 agon|sts 8lLodrln SalbuLamol 1erbuLallne lsoxuprlne
MCA AcL on 2 recepLors cAM producLlon relax uLerlne muscle
Ind|cat|on remaLure labour (wlLh lnLacL membrane)
Adverse Lffects nausea vomlLlng headache palplLaLlons nervousness resLlessness
emoLlonal upseL hypoLenslon lefL venLrlcular fallure pulmonary edema

Cther Drugs that Inh|b|t Uter|ne Contract|on
Calclum channel blocker (eg nlfedlplne)
rosLaglandln synLheLase lnhlblLors (eg LndomeLhacln)
volaLlle agenLs (eg PaloLhane)
SLerolds (eg rogesLerone)
CxyLocln anLagonlsL (eg ALoslban)


Lactat|on Inh|b|t|on Suppress|on
Nonhormona| normona|
Avold breasL nlpple sLlmulaLlon
SupporL breasL ln approprlaLe brasslere
rolacLln Lo nonpregnanL level (414d)
Lngorged breasL paraceLamol (analgeslcs)
LsLrogen +/ LesLosLerone
(anLagonlsL effecLs of prolacLln)
Dopam|ne (D2) agon|st
Cabergollne
ramlpexol
8oplnlrol
8romocrlpLlne (noL allowed anymore)


Drug St|mu|at|on of Lactat|on
SLlmulaLe prolacLlon secreLlon block dopamlnerglc recepLors (procalnamldes)
O MeLoclopramlde (oral)
O Sulplrlde (oral)
SupllmenLlng leL down reflex by oxyLocln nasal spray
8reasL volume no slgnlflcanL adverse effecLs

Gestational Trophoblastic Diseases (GTD)

Definition
Spectrum of abnormalities of trophoblasts associated with pregnancy
Secrete hCG (human chorionic gonadotrophins)
Can be cured with preservation of reproductive function (even malignant)



Epidemiology
Poor nutrition
y Socioeconomic
y Dietary intake of carotin, folic acid
Maternal age <20y/o, >40 y/o (due to defective fertilization)

Hydatidiform Mole
Complete Partial
Contains no fetal tissue Fetal tissue is often present
46, XX (90%) | 46, XY (10%)
Paternal chromosome fertilize empty egg
Duplication of paternal chromosome (adrogenesis)
Grape like tissues packing up uterine cavity
No fetus
Both maternal, paternal origin (69,XXX)| (69,XXY)
Mechanisms
y Haploid egg being fertilized by 2 sperms
y Abnormal diploid sperm fertilize the haploid egg
Smaller vesicles in uterus
May have abnormal fetus
Uterine enlargement larger than expected for gestational age
Caused by excessive trophoblastic growth, retained blood
Pre-eclampsia
Severe hyperemesis gravidarum
Uterus may correspond to date
Do not have same clinical features as those with complete mole
Signs, symptoms consistent with an incomplete, missed abortion
y Vaginal bleeding
y Absence of fetal heart tones
-hCG > 100,000 mIU/mL
Ultrasound
Snowstorm pattern (represent hydropic chorionic villi)
Intrauterine mass contain many small cysts
Histology
Edematous placental villi
Hyperplasia of trophoblasts
No fetal blood vessels
-hCG < 100,000 mIU/mL
Morphology
Fetal tissue present
Chorionic villi contain vessels with fetal RBC (within mesenchyme of villi)
Hydropic (edematous) villi
Trophoblastic proliferation present (but minimal)
Villous scalloping
Trophoblastic inclusions (within mesenchyme of villi)
Homozygous (80%) Heterozygous (20%)

Two identical paternal chromosome
Derived from duplication of paternal
haploid chromosomes
Always female (46YY never observed)
All chromosomes are paternal origin
(due to dispermy)
Male/ female



True (hydatidiform) mole
Enlarged uterus
Thinned out (uterine muscle)
Inside packed with molar tissue
No invasion on wall of uterus
Grape-like


Partial mole
Villi
Normal placental tissue
Clinical Features
Abnormal vaginal bleeding in early pregnancy
Lower abdominal pain
y Toxaemia (before 24w of gestation)
y Hyperemesis gravidarum
y Uterus large for date
y Enlargement of ovary (Theca lutein ovarian cyst)
y Absent of fetal heart tones, fetal parts
y Expulsion of swollen villi
y Trophoblastic embolization (RDs)
Clinical Features
Signs, symptoms of incomplete, missed abortion
Diagnosis by histologic review of curettings



Prognosis
Uterine invasion (15% of patient of complete mole)
Metastasis (4% of complete mole)
Persistent tumour (4% of partial mole)

Follow Up
Monitored for potential development of malignant sequalae
(by serial determination of -hCG)
Risk of GTT with
Large uterus
HCG level
Lutein cyst
History of molar pregnancy
Age > 40y/o
HCG follow up is weekly until ve results (then monthly up to 1 year)
Pelvic examination every 2 weeks until normal (then every 3 months)
Oral contraceptive for 1 year

Placental Site Trophoblastic Tumour
Rare
Consists of groups of mononucleated, multinucleated trophoblastic cell
Cells are human placental lactogen (HPL) +ve > than HCG
Present with chronic vaginal bleeding after delivery
Hysterectomy (treatment)

Invasive Mole
Hydatidiform mole invade uterine myometrium
Metastasize to extrauterine tissues
Biologic behaviour
Invasive mole villus may invade myometrium, blood vessels
Spread locally
Invade myometrium
Penetrate uterine wall
Spread to broad ligament, abdominal cavity
Clinical Manifestations
Irregular vaginal bleeding
Uterine subinvolution
Theca lutein cysts does not disappear after emptying uterus
Abdominal pain
Metastatic focus manifestation


Gestational Choriocarcinoma
Highly malignant tumour
Metastasize (through blood circulation)
Damage tissues, organs
Cause bleeding, severe necrosis
50% gestational choriocarcinoma result from hydatidiform mole
(generally occurs over 1 year after emptying mole)
y cases after molar pregnancy
y cases after normal pregnancy
y cases after abortion, ectopic pregnancy
Common metastatic site
Lung (most common)
Vagina
Brain
Liver
Clinical Manifestations
Vaginal bleeding
Pain
Uterine enlargement
Mass

Pathology
Gross Histology
Large mass in uterus
Diameter 2-10cm
Massive necrosis
Hemorrhagic
Cancer embolus
y Paarauterine veins
y Ovarian
Luteinizing cyst
(formed in ovaries)
Cytotrophoblastic, syntrophoblastic cells invade
myometrium, vessels

Severe necrosis, hemorrhage
Few viable cancer cells



FIGO Classification
Stage Details
I Confined to corpus
II Metastasis outside uterus to vagina, pelvic structure
III Metastasis on lungs
IV Distant metastasis

Management
Chemotherapy
Surgery

Differential Diagnosis of Bleeding in Early Pregnancy
Abortion (different type)
Ectopic pregnancy
Molar pregnancy
Partial mole
Choriocarcinoma
Blood diseases
Local causes

Ectopic Pregnancy

Ectopic Pregnancy
Pregnancy outside uterus
Commonest site ovary

Risk Factors
Pelvic inflammatory disease (PID)
Endometriosis
History of prior ectopic pregnancy
History of tubal surgery, conception after tubal ligation
Clinical Features
Pregnancy symptoms
Depending on site RIF, LIF
Emergency
Acute tenderness
Shock (if ruptures)


Normal Labour

Definition
Spontaneous regular painful uterine contractions
Effacement, dilatation of cervix
Descent of head in a vertex presentation
Expulsion of fetus, placenta

Terminology
Lie
Relationship of long axis of fetus to long axis of uterus
Longitudinal, oblique, transverse

Longitudinal

Transverse

Longitudinal
Presentation
Pole of fetus that presents at pelvic brim
Cephalic, vertex, face, brow, podalic, shoulder
Malpresentation other than vertex
Position
Relationship which some selected part (denominator) of fetus bears to the
maternal pelvis
Vertex occiput
Face chin (mentum)
Breech sacrum
Positions LOA, ROA, ROP, LOP, LOT, ROT

Attitude
Relation of different parts of fetus to one another
Station
Level of presenting part in relation to ischial spine
0 station (zero station) top of head at level of maternal ischial spines
Engagement
Engaged (completely engaged) widest portion of fetal head has entered
pelvic inlet




Pelvic Floor
Formed by 2 levator ani muscles, with their fascia
As a musculofascia gutter during 2
nd
stage of labour


Perineum
Perineal body
Condensation of fibrous, muscular tissue lying between vagina, anus
Received attachments of
y Bulbo-carvenous muscle (posterior ends)
y Superficial, deep transverse perineal muscles (medial ends)
y External anal sphincter (anterior fibre)


Pelvis
Pelvic Brim (Inlet of Pelvis) Pelvic Mid-Cavity Pelvic Outlet
Inlet of pelvis
Rounded/ oval transversely
No undue projection of sacral promontory

AP diameter 11cm
Transverse diameter 13.5cm
Angle of inlet 60% to horizontal in erect position
Boundaries
Front symphysis pubis (middle)
Sides pubic bone, obturator fascia, ischial bone
Posterior junction of 2
nd
, 3
rd
sections of sacrum

Rounded
Transverse, AP diameter are similar 12cm
No great projection on ischial spines
Smooth sacral curve
Boundaries
Front - symphysis pubis (lower margin)
Sides
y Descending ramus of pubic bone
y Ischial tuberosity
y Sacrotuberous ligament
Posterior sacrum (last piece)

AP diameter 13.5cm
Transverse diameter 11cm


Fetal Skull
Made up of vault, face, base

Degrees of Moulding



Fetal Attitude



Fetal Diameter


Uterus


Onset of Labour
Regular contractions bringing about progressive cervical change

Stages of Labour
1
st
Stage (Dilatation) 2
nd
Stage (Expulsion of Fetus) 3
rd
Stage (Placenta)
From diagnosis of labour to full dilatation of cervix Lasts from full dilatation of cervix to fetus is born Lasts from birth of child until placenta, membranes
are delivered
Uterus retracted firmly to compress uterine blood
sinuses
In a normally shaped pelvis, position of occiput is
y Transverse diameter (75%)
y Oblique (14%)
y Direct anterior (3%)
y Posterior diameter (8%)
Active phase starts when 3-4cm
Cervix becomes fully effaced

Should not last more than
y 2h (in primid)
y 1h (in multipara)
Use of epidural may influence
length, management of 2
nd
stage
Placenta is usually delivered within a few minutes of
birth of the baby
Should last < 30mins (if >30 mins, abnormal)
Cavity of uterus becomes smaller
Uterine contractions expel placenta
(upper segment lower segment vaginal vault)
Retraction of uterus compress uterine sinuses
Uterus felt as hard round ball
(top of uterus just below umbilicus)
Generally <500ml blood loss
Latent Phase
Lasts 3-8h (shorter in multiparous women)
Passive Phase
No maternal urge to push
Fetal head still relatively high in pelvis
Signs of Placental Separation
Lengthening of cord
Gush of blood from vagina
Uterus rises, contracts in abdomen
Uterus becomes hard, globular
Active Phase
Time between end of latent phase & full dilatation
Variable in length
Lasting 2-6h
Dilatation rate 1.0cm/hr (in normal labour)
Fetus does not move downwards to any great degree
Bag of membrane may remain intact
(until nearly end of 1
st
stage)
Active Phase
Maternal urge to push (because fetal head is low)
Active Management of 3
rd
Stage
Post Partum Haemorrhage
Oxytocic drug (syntocinon/ syntometrine)
Early cord clamping
Control cord traction (CCT)(when contraction felt)
(Uterine inversion if CCT with absent of contraction)
Completion of 3
rd
Stage
Inspect placenta
y Missing cotyledon
y Succenturiate lobe
Vulva inspected tear, lacerations

Position of Vertex on Onset of Labour


Cervix Taken Up, Dilated During Labour

Duration of Labour


Uterus



Mechanism of Labour (Vertex presentation, Gynaecoid pelvis)
Engagement
Head enters pelvis in transverse position
Engagement occur in majority of nulliparous prior to labour
(but not for majority of multiparous)
If >2/5
th
of fetal head palpable head is not yet engaged

Head Transverse diameter (Occiput to left (LOT))
Descent
1
st
stage, 2
nd
stage of labour descent of fetus is 2 to uterine contraction
Flexion
Minimize presenting diameter of fetal head
Internal rotation
If head is well flexed
Rotate anteriorly sagittal suture lies in the AP diameter of pelvic outlet
(widest diameter)

Extension
Crowning of head
Minimize soft-tissue trauma (utilize smallest diameters of head for birth)

Restitution
Occiput is directly anterior (when head is delivering)

Rotation of head to natural position
(relative to shoulders, as soon as it is (head) completely born)
External Rotation
Shoulders have to rotate into the direct AP plane

Delivery of Shoulders, Fetal body
Shoulders will be in AP position
Anterior shoulder under symphysis pubis (delivers first)
Posterior shoulder delivers subsequently


Mechanism of Labour (cont.)


Episiotomy
Surgical incision of perineum - diameter of vulva outlet (during childbirth)
Associated with
y Unsatisfactory anatomical results
y Blood loss
y Perineal pain
y Dyspareunia
Techniques midline, mediolateral
Indications
y Fetal distress
y Short perineum
y Shoulder dystocia
y Fetal malposition (eg. occipito-posterior)
y Instrumental, breech delivery
y Previous pelvic floor surgery

Pathophysiology of Onset of Labour
Myometrial function
Efface, dilate cervix - drive fetus through birth canal
3 properties
y Remain quiescent (during pregnancy, suppress contraction until time)
y Adequate periods of relaxation between contractions during labour
y Capacity for retraction
Hormonal factors
Progesterone maintain uterine quiescence
y Suppress prostaglandin (PG) production
y Inhibit communication between myometrial cells
y Prevent oxytocin release
Prior to labour
y Progesterone receptors
y Estrogen
Oxytocin + PG cause
y Ca2+ influx into myometrial cells
Cervix
Proteolytic activity, collagen turnover
Dermatan sulphate (H2O content of cervix) cause ripening of cervix
(cervical softening)

Biological Control of Labour
Trigger for parturition (comes from fetus)

Maturing fetal brain release corticotrophin
(from fetal pituitary gland)

Fetal adrenal gland release cortisol, dehydroepiandrosterone sulphate

Cortisol cause change in composition of amniotic fluid
Provoke release of PGE2 from amnion

Provoke release of PGF2 (from decidua)
Exciting myometrial contractions

Fetal Assessment in Labour
Observation of colour of liquor
y Fresh meconium staining
y Heavy bleeding
Intermittent auscultation of fetal heart
y Pinard stethoscope
y Hand-held Doppler ultrasound
Continuous external fetal monitoring (EFM) using cardiotocography
Fetal scalp blood sampling (FBS)

Obstetric Analgesia & Anaesthesia

Pain Pathway during Labour


Pain
1
st
Stage of Labour 2
nd
Stage of Labour
Uterine contraction
Cervical dilatation
Perineal stretching
Somatic nerves
Pudendal nerve
Posterior cutaneous nerve of thigh
Ilioinguinal nerve S2,3,4
Pathways
Sympathetic pathway T10-L1
Referred pain to cutaneous T10-L1
Lumbosacral plexus L5S1
Sites of pain
Early 1
st
stage T11-T12
Late 1
st
stage T10-L1
Backache
Sites of pain
Perineal region
Sacral region

Stress Response to Pain in Labour
CVS
Maternal CO ( stroke volume, heart rate)
Greatest increase in CO immediately after delivery
y Venous return
y Relief of venocaval compression
y Autotransfusion (resulting from uterine involution)
Respiratory
Hyperventilation (due to pain in labour)
Maternal hypocarbia
Respiratory alkalosis
Compensatory metabolic acidosis
O2-dissociation curve shift to left - O2 transfer to tissue
(compromised by O2 consumption associated with labour)
Hormonal
Release of -endorphine, ACTH from anterior pituitary (due to pain, anxiety)
Adrenaline, Noradrenaline (from adrenal medulla)
(lead to progressive rise in peripheral resistance, cardiac output)
Activation
Sympathetic Activity Autonomic Nervous System
Incoordinate uterine action
Prolonged labour
Abnormal fetal heart-rate patterns
Delays gastric emptying
Intestinal peristalsis
Metabolic
Maternal Fetal
Glucagon, GH, Renin, ADH
Insulin, testosterone
Maternal catecholamines secreted
(cause fetal acidosis)


Ideal Labour Analgesia
Maternal, fetal safety
Ease of administration
Consistent, predictable, rapid onset
Maternal composure, control during 1
st
, 2
nd
stages of labour
Analgesia through all stages of labour
Devoid of motor blockade, enable ambulation, various birthing positions
Preserve stimulus for expulsive efforts during 2
nd
stage of labour
Retain maternal expulsive efforts
Facilitate delivery of supplemental analgesia (without additional invasiveness)
Facilitate delivery of analgesia for surgery (avoid need for general anaesthesia)



Systemic Medication
Benzodiazepines
Benefits Adverse Effects
Anxiolytics
Adjuvant to narcotics
Premedicant to LSCS
Preeclampsia, eclampsia
Hypotonia
Lethargy
Feeding
Hypothermia
Beat to beat variability of fetal heart
Maternal sedation (minimal fetal respiratory depression)
Crosses placenta
No adverse effects on acid-base, clinical status
Opioids (Pethidine, Morphine, Fentanyl, Remifentanil)
Adverse Effects
Maternal Fetal
Drowsy, sleepy
Nausea, vomiting
Suppress cough reflex
Respiratory depression
Antidote Naloxone (at birth)

NSAIDs
Paracetamol
Mefenamic acids
Cox 2 Inhibitors Celecoxib, Valdecoxib
Indications
y Perineal pain after delivery
y Post-caeserean section
y Contraction pain post delivery
Some amount secreted via breast milk (not significant level in baby)
Inhalation Agents (Nitrous oxide, ENTONOX NO:O = 50:50)
Pain relief in 1
st
, 2
nd
stages of labour
Not Associated With Benefits
Uterine tone
Strength of contractions
Responsiveness to oxytocins
Neonatal acid-base status
Respiration
Oxygenation
Apgar scores
Neurobehaviour score
Self administered
Rapid onset, offset
No accumulation in mother
No effects on uterine contraction
No effect on oxytocics responsiveness
No change in
y Neonatal acid-base status
y Respiration
y Oxygenation
y Apgar scores
y Neurobehaviour score


Alleviation of Labour Pain
1
st
Stage 2
nd
Stage
Lumbar epidural
Intrathecal block
Bilateral paracervical blocks
Bilateral lumbar sympathetic blocks at L2
Bilateral paravertebral blocks (T10-L1)
Low epidural
Caudal
Spinal saddle block
Bilateral pudendal nerve blocks

Labour Epidural
Indications Contraindications
Maternal request, distress
Induction of labour
Breech presentation
Twins, multiple pregnancy
Occipito-posterior position
PIH+/- proteinuria
Prematurity
IUGR, fetus small for gestational age
Previous caesarean section
Induction of labour
Forcep delivery
Absolute
Sepsis
Bacterimia
Skin infection at injection site
Severe hypovolaemia
Coagulopathy
Therapeutic anticoagulation
Patient refusal
Relative
Peripheral neuropathy
Mini dose heparin
Psychoses
Aspirin, antiplatelet drugs
Demylinating CNS disease
Idiopathic hypertrophic subaortic
stenosis
Aortic stenosis
Psychological, emotional instability
Uncooperative patient


Continuous Epidural Infusion
Advantages Complications
Fluctuations in pain relief level
Amount of motor blockade
Hypotensive episodes
Not required to repeat test dosing
(frequent monitoring)
Overdose, high blockade
Segmental blockade
Subarachnoid catheter migration
Intravascular migration
Complications
Hypotension
Inadequate analgesia
Intravascular Injection
Unintentional dural puncture
High block
Catheter misplaced into subarachnoid space
Urinary retention
Back pain
Maternal fever
Progress of labour

Regional Anaesthesia
Advantages Disadvantages
Awake patient
y Improved maternal-child bond
y Husband friendly
Avoid problems of GA
y Airway, aspiration risk
y Multiple drug administration
Provide effective post OP analgesia
( Thromboembolic phenomena)
Sympathetic blockade
(with hypotension)
Incomplete, patchy block
Limited duration in spinal epidural
Complications
Inadvertent intravascular injection
Dural puncture

Spinal Anaesthesia
Advantages Complications
Simplicity with definite end-point
Minimal drug usage
Rapid onset
Reability
Dense motor, sensory block
Hypotension
Excessive spread, high spinal anaest.
Post-dural puncture headache
Incomplete anaesthesia
Nerve injury (rare with spinal below L2)
Infection

General Anaesthesia
Advantages Disadvantages
Shorter induction time
Lower failure rate
Better CVS control
Full control of respiratory functions
Rapid control of convulsion
No patient cooperation required
Difficult airway management
Risk of regurgitation
(pulmonary aspiration)
Awareness
GA related problems
y PONV
y Hangover effect
y Lack post OP analgesia
Stress response during induction
(emergence)

Breast Pathology

Anatomy

Terminal Ductal Lobular Unit (TDLU)


Fibrocystic Disease of Breast
Benign proliferative breast disease
20-45 y/o (very common)
Lumpy breast
Pain in lumps during menses
Bilateral (often)
Lumps non discrete
Affects TDLU


Fibrocystic ds of breast
Cystic change
Epithelial proliferation
Fibrosis

Fibroadenoma
20-35 y/o (very common)
Mobile lump (breast mouse)

Fibroadenoma
Single
Sharply demarcated
Mobile lump (breast mouse)

Fibroadenoma
Proliferation of stroma
Proliferation of ductular structure



Phyllodes Tumours
Biphasic (difficult to distinguish from fibroadenoma clinically)
Suspect if
> 40 y/o
> 4cm
History of recent growth
Problems
Local recurrence after excision
Malignant transformation with metastatic potential (rarely)


Phyllodes Tumours
Cellular stroma
Slit-like spaces
(lined by ductal epithelial cells)

Benign Fibrocystic Changes

Benign Fibrocystic Changes
Cysts

Benign Fibrocystic Changes
Cysts
Calcium
Apocrine metaplasia

Radial Sclerosing Lesions


Benign Intraductal Papilloma


Benign Tumours Intraductal Papilloma




Breast Carcinoma

Symptoms
Any new lump
Nipple discharge (bloody, dark, occurs without squeezing nipple)
Nipple drawing inward, pointing in a new direction
BSE


Risk Factors
Female (1% Male)
Aging
Relative (mother, sister on maternal, paternal sides)
Menstrual history early onset, late menopause
Child birth
y > 30 y/o
y Having a 1
st
living child at late age
y Never given birth to a living child
Having few pregnancies
Family member colon, uterine, ovarian cancer
Exogenous estrogen
y Hormone replacement therapy (HRT) (long term use)
y Oral contraceptives (start at young age)
Radiation exposure
Breast disease
y Atypical hyperplasia
y Intraductal carcinoma in situ
y Intralobular carcinoma in situ
y Previous breast cancer (whether or not spread to surrounding tissues)
Obesity
Diet fat, alcohol
Genetics
y BRCA-1
y BRCA-2
y P53, Rb-1
y Her-2/neu, c-erB2, c-myc
Exercise
2 Alcoholic drinks/ day
Weight excessively after 18y/o



Distribution of Breast Cancer
Left breast ( common)
50% - Upper outer quadrant
20% - Central/ subareolar
10% - Remaining quadrants
4% - Bilateral

Staging of Breast Cancer (TNM)
Stage I Stage II Stage III
Size 2.0cm Size 2-5cm Size >5cm (T3)
No nodal involvement (N0) Ipsilateral axillary l/n (N1) Ipsilateral axillary l/n fixed
to each other, other
structures (N2)
Involve ipsilateral internal
mammary nodes (N3)
No metastases (M0) No metastases (M0)
Inflammatory carcinoma
(T4d)

Classification (WHO)
In-situ
Invasive
y Invasive ductal ca NOS
y Invasive lobular ca
Type
y Medullary ca
y Colloid ca
y Mucinous
y Tubular ca
y Adenoid cystic ca
y Pagets disease
y Apocrine ca
y Invasive papillary ca


Malignancy
In Situ Invasive
Ductal Carcinoma in Situ (DCIS)



DCIS


Classic Lobular Ductal
Bilateral multifocal Often Often
ER PR Receptor + +ve
E cadherin -ve +ve
Metastatic pattern GI
Meningitis
Peritoneum
Ovary

Invade diffusely
(with little fibrosis)
Often

Lobular Carcinoma in Situ (LCIS)



LCIS



Morphology

Breast Carcinoma
Retracted overlying skin
Irregular tumour mass

Infiltrative Ductal Ca
Infiltrating tumour cells
Desmoplastic reaction

Infiltrating Lobular Carcinoma

Spread
Direct
Lymphatics
(Axillary l/n)
Blood
Skin
Nipple
Pectoralis muscle
Chest wall
Low (proximal) axillary l/n
Medium (middle) axillary l/n
High (distal) axillary l/n
Supraclavicular l/n
Bones
Lungs
Liver

Sentinel Node
Metastasis follow a pathway of drainage
Sentinel node is 1
st
node which received carcinoma cells




Predictive & Prognostic Factors of Breast Carcinoma (Category 1)
TNM Staging
Histologic type
Histologic grade
y Tubular formation
y Nuclear pleomorphism
y Mitotic count
Hormone receptor status (ER/ PR)
C-erbB2 (Her 2-neu)
ER/ PR Predictive Factors
ER+, PR+ has the best response
Reporting
y Should be done on primary tumours
y May be done on nodes (metastatic sites) if primary sites not available
(20-30% of ER+ primary has ER- metastasis)
y Include controls (normal breast epithelium)
y % of + nuclei
Conversion of hormone status
y ER+ ER- (29% often <1 yr)
y ER- ER+ (33% beyond 3yr)

Normal

Carcinoma

HER2 (c-erbB-2) over expression
Human epidermal growh factor receptor 2
Overexpressed in
y Infiltrating carcinoma (20-30%)
y DCIS (60%)
No expression in
y Normal epithelium
y Hyperplastic epithelium
y Dysplastic epithelium
Carcinoma with Her2+
y Sensitive to anthracyclines
y Less responsive to tamoxifen
Her2 not modified by pre-chemotherapy (stable during metastasis process)

Screening
Mammography
y 60% +ve mammograms are palpable lesions
y Detects microcalcification in breast carcinoma (50-60%)
Detects microcalcification in benign (<20%)
Breast Self Examination (BSE)



Contraception

Fertility Awareness Methods

Calendar Method (Rhythm Method)
Based on assumption that menstrual cycle relatively constant
Pregnancy rate 40/100 women years
Rule
Record length of 6 cycles
Estimate
Beginning of Fertile Period End of Fertile Period
Substracting 20d from length of
shortest cycle
Substracting 10d from length of
longest cycle



Cervical Mucus Method (Billing Method)
During follicular phase, cervical mucus appear like raw egg white (fertile)
Final day of fertile mucous most likely ovulation occur
Abstinence from start until 3d after peak day
Appearance of infertile mucus scanty, viscous (end of fertile period)
Failure rate 22/100 women years


Symptothermal Method
Basal body temperature recorded before getting out of bed
Progesterone secretion associated with 0.5C
Prior to ovulation, temperature is below normal body temperature
Abstinence until night of 3
rd
day of a shift in temperature


Personal Fertility Monitoring (PERSONA)
Measure levels of LH, estrogen-3-glucoronide (early morning urine)
Red light intercourse should be avoided
Need to be programmed for 3 months
Need to be programmed after post-coital contraception
Failure rate 6/100 women years (with perfect use)


Minor Clinical Indicators
Ovulation pain (Mittelschmerz)
Mid cycle show of blood
Onset of breast symptoms
Skin, mood changes

Lactational Amenorrhoea Method
Breast feeding amenorrhoiec during 1
st
6 months (after giving birth)
2% of still getting pregnant



Oral Contraceptive Pills

Combined Oral Contraceptive Pills (COCP)
Preparation
Ethynil estradiol
Progesterone levonorgestrel, desogestrel, gestodene, norgestimate
MOA
Suppress ovulation
y Prevent ovarian follicular maturation
y Interrupt estrogen-mediated +ve feedback prevent LH surge
Thicken cervical mucus ( permeability of sperm)
Alteration of endometrium ( implantation likelihood)

Advantages/ Disadvantages
Advantages Disadvantages
High efficacy (0.1-3/100 WY failure)
Reversible
Not related to intercourse
Menstrual blood flow (IDA)
Dysmenorrhoea
( prostaglandin - contraction)
Predictability of menses
PMS
Breast disease (benign)
Ovarian cyst (functional)
Ectopic pregnancy
Ovarian, endometrial cancer
Thromboembolic disease
y Venous thrombosis
y Myocardial infarction
y Stroke
Breast cancer
Cervical cancer
Liver adenoma, carcinoma
Cholestasis
Gallstones


Progestogen-Only Pills (POP)
Uses
Suitable For Contraindication
VTE
Migraine
Older women
Smoke
Hypertension
Valvular heart disease
Diabetes mellitus
Pregnancy
Vaginal bleeding (undiagnosed)
Severe arterial disease
Liver adenoma

MOA
Thicken cervical mucus ( permeability of sperm)
Receptivity of endometrium to implantation
Ovulation
Fallopian tube motility

Advantages/ Disadvantages
Advantages Disadvantages
High efficacy (0.3-5/100 WY failure)
Effective when used correctly
Well tolerated
No estrogen side effects
Reversible
Efficacy with age, if >70kg
Do not affect FSH, estradiol levels
(associated with menopause)
Strict adherence
Pattern of bleeding unpredictable
Ovarian follicular cysts
Ectopic pregnancy



Injectable Contraception

Preparations
Depo-Provera Noristerat
Depot medroxyprogesterone acetate Norethisterone enantate
Deep IM injection
Every 3 months +/- 2 weeks
Failure rate 0.25-0.5/100 WY
Every 8 weeks +/- 2 weeks
Less effect on bleeding pattern
0.4-2.0/100 WY



MOA
Inhibition of ovulation
Effect on endometrial, cervical mucus

Benefits/ Risks
Benefit Side Effects/ Risks
Those forgot to take pills (travellers)
Estrogen contraindicated patients
Sickling crises (sickle cell disease)
Seizures (epileptic women)
No effect on ovarian, endometrial ca
No association with stroke, MI, VTE
( HDL)
Irregular frequent vaginal bleeding
Amenorrhoea
Weight
Headache, dizziness
Breast tenderness
Mood changes
Delay in return to normal fertility


Implants

Implanon
Etonorgestrel (active metabolite of desogestrel)
Single rod implant, biodegradable
Effective for 3 years (lower for overweight women)
MOA
Inhibit ovulation (prevent LH surge)
Affect cervical mucus thickening, endometrium

Benefits/ Risks
Benefits Side Effects
Failure rate < 0.1/100 WY
Independence of user compliance
Rapid return to fertility
Efficacy not affected by antibiotics
Menstrual disturbances
Alopecia, emotional lability
Depressive symptoms, dysmenorrhea
Headache, acne, breast pain


Norplant
6 capsules labelled for 5 years usage
Failure rate 0.2-1/100 WY



Intrauterine Contraceptive Devices (IUD)

Copper IUCD
Licensed for 5 years (Multiload Cu 375)
Complications
Expulsion (occur in 1
st
year, especially 1
st
3 months)
Perforation
Pelvic infection (PID)
Menstrual loss
Abdominal pain, dysmenorrhoea
Pregnancy (remove as soon as diagnosed - miscarriages)


Gynefix
Licensed for 5 years
Inserted by those who have received appropriate training
Similar efficacy to Cu T 380 ( expulsion rate)


LNG-IUS (Mirena)
Long-acting, rapidly reversible
Frame is radio-opaque (barium sulphate)
Licensed for contraception for 5 years
MOA
Endometrial glandular, stromal atrophy (decidualization effect)
Change in cervical mucus (prevent ascent of spermatozoa)

Advantages/ Disadvantages
Advantages Disadvantages
Rapid return to fertility
Management of menorrhagia
( Menstrual blood loss)
Dysmenorrhoea
Ectopic pregnancy
Endometrial hyperplasia management
Protection against STD
y Thickening of cervical mucus
y Inactivation of endometrium
y Bleeding
Cost effectiveness
Difficulty insertion (nulliparous)
Irregular bleeding
Amenorrhoea
Functional ovarian cysts
Progestogenic side effects
y Edema
y Headache
y Breast tenderness
y Acne
Expulsion



Barrier Method

Condom (Male)
Failure rate 2-15/100 WY
Advantages/ Disadvantages
Advantages (Polyurethane) Disadvantages
Baggier, less restrictive around
glands (more sensation)
Lack of sensitivity around
glands of penis
Not affected by fat soluble products
(baby oils cause breakage)

Reasons for Condom Failure
Put on after genital contact
Not completely unrolled onto penis
Slippage (when penis withdrawn from vagina, during sexual intercourse)
Breakage
Oil-based lubricants (inc. lipsticks) (latex condom break)
Mechanical damage (eg. fingernails)
Concurrent use of vaginal preparations of drugs


Female Condom (Femidom)
Lines the vagina
1 size
Design for single use, expensive
Failure rate 5-20/100 WY


Diaphragm
Thin, latex rubber hemisphere
Use with spermicidal ( effectiveness)
Causes of failure
Poor motivation
Incorrect insertion
Displacement during sexual intercourse
Failure rate
4-8/100 WY (with spermicidal)
10-18/100 WY (without spermicidal)


Cervical Cap (FEMCAP)
Nonallergic silicone rubber
Stop sperm from entering cervix
Failure rate 8-20/100 WY


Spermicide
Kills sperms
Unscented, clear, unflavoured, non-staining, lubricative
Nonoxynol-9


Contraceptive Patches/ Ring

Ortho-Evra / Evra
Transdermal patch upper outer arm, buttocks, abdomen, thigh
Patch change day day of application
Applied once weekly for 3 consecutive week, followed by a patch-free week

Advantages/ Disadvantages
Advantages Disadvantages
Continuous, sustained release of drug
Avoids peaks, trough drug levels
Longer, multiday dosing interval
Avoid 1
st
pass hepatic metabolism
Avoid enzymatic degradation by GIT
Compliance ( frequent dosing)
Alternative to oral route
Stop with patch removal
Dose delivery unaffected by vomiting
Nausea
Vomiting
Application site reaction
Breast discomfort, engorgement, pain
Headache
Emotional lability


Nuva Ring
Flexible plastic release low dose progestin, estrogen 3 weeks
Insertion of ring into vagina (3 week period), then remove 1 week(menstrual)
Advantages
Once-a-month self-administered use (convenience, ease, privacy)
Lower estrogen exposure (than COCP, ortho evra)
Side effects nausea, breast discomfort
Irregular bleeding (despite lower estrogen dose)



Sterilization

Bilateral Tubal Ligation (BTL)
Advantages Disadvantages
99% effective
Various approach
Difficult to reverse (permanent)
Ectopic pregnancy (33% chance)
Risk to anaesthetic, surgical complications
More difficult than vasectomy
Cost


Vasectomy
Advised to use contraception until azoospermia is confirmed
Failure rate 1/2000 (compared to 1/200 in BTL)
Not associated with
y Testicular cancer
y Heart disease
Develop antisperm antibodies (75% of men)



Drugs That Modify Fertility

Enhance Fertility
Female Male
Prolactine producing adenoma
Dopamine agonist
y Bromocriptin
y Pergolide
y Cabergoline
Anovulation
GnRH agonist (short acting pulsatile)
y Gonadorelin
y Leuprolide
SERMs clomiphene citrate
FSH, LH
y Urofollitropin
y Follitropin
Poor sperm production
Anti-estrogen
y Clomiphene
y Tamoxifen
Androgen (mestrolone)
Hypogonadism
GnRH agonist (short acting, pulsatile)

Dopamine Agonist
Bromocriptin
Pergolide
Cabergoline
MOA
Inhibit prolactin release
Adverse Effects
Nausea
Postural hypotension
Contraindication
Hypersensitivity to ergots

SERMs (Selective Estrogen Receptor Modulators)
Tamoxifen Raloxifene Clomiphene
Breast cancer Osteoporosis
(treatment, prevention)
Induce ovulation
Adverse Effects
Hot flashes
Libido
Endometrial cancer
Adverse Effects
Hot flashes
DVT
Adverse Effects
Ovary size
Hot flashes
Nausea, vomiting
Twin pregnancy
Estrogen antagonist
Breast tissue
Partial agonist
Endometrium
Bone
Estrogen partial agonist
Bone
Antagonist
Breast
Endometrium
Estrogen antagonist
Hypothalamus
Partial agonist
Ovary

GnRH Agonist
Pulsatile mimic natural secretary pattern
(Stimulate FSH, LH release )(stimulate ovulation)
Gonadoreline
Goserelin
Adverse Effects
y Nausea
y Abdominal discomfort
y Headache
y Flushing
y Local pain
y Thromboplebitis
Continuous administration, long acting
( Gonadotropin, Sexual hormones)
Goserelin
Histrelin
Leuprolide
Nafareline
Clinical Uses
y Prostate cancer
y Endometriosis
y Precocious puberty
y Male contraception
Adverse Effects
y Hot flushes
y Osteoporosis
y Sexual dysfunction

FSH, LH
HMG FSH, LH (prepared from urine of post-menopausal women)
HCG LH-like properties (prepared from urine of pregnant women)
Adverse Effects
Allergic reaction
Ovarian hyperstimulation (abdominal discomfort)
Multiple gestation



Contraception
Prevention of
Production of spermatozoa
Delivery of spermatozoa into female genital tract
Follicular growth, ovulation
Oocyte passage through fallopian tube
Fertilization
Implantation


Types of Contraceptions
Female Male
Natural
Abstinence
Rhythm methods
Breast feeding
Mechanical
Female condom
Diaphragm
IUCD
Drugs
Oral contraceptive COCP, POP
Long acting progestins
(depot, subdermal, implant)
Surgery
BTL
Natural
Abstinence
Coitus interruptus
Mechanical (Barrier)
Male condom
Drugs
GnRH analog
Gossypol
Surgery
Vasectomy


Combined OCP
Taken for 21 days followed by a 7-day break allow withdrawal bleeding
(mimic normal mensus)
Continuously eg. 3 cycles
Drug content
Estrogen Progestogen (Progestin)
Ethinyl estradiol
Microgynon
Mestranol
Levanogestrel
Norethistrone
Norgestrel
Types of Preparation
Monophasic constant dose
Biphasic, Triphasic
Dose High, Medium, Low
Hormones That Control Ovulation (-ve Feedback Mechanisms)

Estrogens & Progestogens
Estrogen Progestogen
Strongly suppress FSH
(prevent follicle development)
Thicken cervical mucous
(sperm cannot pass through)
Suppress LH release
(prevent ovulation)
Inhibit endometrial development
(prevent implantation)
Weakly inhibit implantation Weakly suppress FSH
(prevent follicular development) Not advisable to be used alone
(combine with progesterone) Weakly suppress LH
(prevent ovulation)

Benefit
Highly effective (99-100%) (require regular consumption)
Regular withdrawal bleeding
Improves gynaecological problems
y Dysmenorrhoea
y Irregular menses
y Endometriosis
Blood loss during menses
Ovarian, endometrial cancer risk
Adverse Effects
Estrogen Progestogen
Thromboembolic risk
(IHD, MI, Stroke, DVT, PE)
Breast, cervical cancer
Hepatoadenoma
(benign liver tumour)
Headache
Nausea, vomiting
Weight
Acne
Minor adverse effects
Break-through bleeding
Weight
Headache, migraine
Acne
Dry eyes
Loss of libido (androgen inhibition)
Skin pigmentation
Vaginal infection
Vaginal secretion

Contraindication
Hypertension
Diabetes
Stroke
IHD
Smoking (35 y/o)
Thromboembolism
Impaired liver function
Breast cancer/ estrogen dependent tumour
Pregnancy/ suspected pregnancy
Undiagnosed vaginal bleeding
Breast feeding
Severe migraine
Drug Interactions
Antituberculosis antibiotic (Rifampicin)
Antiepileptic (Phenytoin, Phenobarbitone)

Progestogen Only Pills (POP)
Norethindrone (0.35mg)
Daily (no off-day)
Efficacy 97-98%
Suitable for breast feeding women
Effects
Prevent follicular maturation
Inhibit ovulation
Changes in cervical mucosa, cervical secretion, endometrium
Adverse Effects
Irregular bleeding (frequent 25% of users)

Long Acting Progestogens
IM 3 month injection (depot medroxyprogesterone acetate)
Effects
Inhibit ovulation
Change in endometrium, cervical mucosa, secretion
Adverse Effects
Prolong amenorrhoea
Temporary infertility after discontinuation
Progestine Implant (eg. L-norgestrel)
Multiple capsules implanted under skin (subdermal implant)
Irregular bleeding
Last for 3 years (can be removed earlier)

Intrauterine System (IUS)
Eg. Mirena
Plastic IUD no copper
Release progestogen to act locally
Bleeding
Prevent systemic adverse effects of progesterone
Effective 99.9%

Post Coital Contraceptives
Dose Estrogen alone/ combination with progestin (COCP, PC4) or POP
Not for regular use
Effective 97-99%
Effects
Motility of Fallopian tube
Prevent fertilization, implantation
Associated with
Nausea, vomiting
Headache
Dizziness
Abdominal, leg cramps


Males Hormones Negative Feedback Mechanism


Androgen
Effects
Inhibits sperm production
Sperm count to 3x10
6
/ml (oligospermia)
Inhibits FSH, LH productions
Adverse Effects
Acne
Weight
Oily skin
Libido

GnRH Agonist
Dose/ Extra-long-acting products
Effects
Sensitivity of anterior pituitary to GnRH
GnRH receptors in pituitary (down regulation)
Adverse Effects
Headache
Nausea
Libido

Gossypol
Cottonseed derivative
Effects
Destroys elements of seminiferous tubules
(Does not alter endocrine function of testis)
Adverse Effects
Hypokalaemia


Natural Family Planning

Life-span for sperms 3-4 days (may reach up to 7 days for very fertile couple)
Life span for ovum +/- 12 hours


Intrauterine Infections

STORCH
Syphilis
Toxoplasmosis
Others
Rubella
Cytomegalovirus
Herpes
Hepatitis B
Human Immunodeficiency Virus (HIV)
Human Papilloma Virus (HPV)
Human Parvovirus
Hepatitis C



Syphilis
Treponema pallidum
Transmission
Mother-to-child (during fetal development)(vertical transmission)
Birththrough placenta
Congenital Syphilis (CS)
Early CS Late CS
Diagnosed during 1
st
2 years of life
Includes stillbirths
Present after 2 years of life
Manifest near puberty
Asymptomatic at birth
Early-stage symptoms
Irritability
Failure to thrive
Fever (non-specific)
Rash
Lesions mouth, anus, genitalia
Affects bones, teeths, CNS
Watery nasal discharge
Saddle nose (deformity cartilage)
Bone lesion humerus
Hutchingson teeth
Saber shins
Blindness
Deafness

Investigations
VDRL (Venereal Diseases Research Laboratory)
RPR (Rapid Plasma Reagin)
TPHA (T. pallidum haemagglutination assay)
TPPA (T. pallidum particle agglutination assay)
FTA-ABS (Fluorescent treponemal antibody absorption test)
Treatment
Penicillin

Toxoplasmosis
Toxoplasma gondii
Transmission
Congenital Toxoplasmosis (infection transmitted to fetus during pregnancy)
Immunodeficiency AIDS (infection, reinfection of toxoplasmosis)
Mother Infected in Pregnancy
Earlier Later
Risk of infection of fetus
Severe disease
Risk of infection of fetus
Severe disease (subclinical)

Severity of Infection
Subclinical Overt
Late onset symptoms
(chorioretinitis)
No symptoms at all
Abortion
Classical Triad
Chorioretinitis
Intracranial calcification
Hydrocephalus

Investigations
Serological diagnosis
Serological screening (detect asymptomatic infections)
Serological tests IgG, IgM
Amniocentesis PCR technique
y PCR +ve fetus had infection, should be treated
y PCR ve fetus not yet infected, mother receive ATT
Ultrasound hydrocephalus, intracranial calcifications


Congenital Rubella Syndrome
Togavirus (genus Rubivirus)
Transmission
Infect and replicate in placenta
Major Manifestation
Tissue destruction
Scarring
Congenital Rubella Syndrome (CRS)
Abortions
Miscarriages
Stillbirths
Severe birth defects
Signs & Symptoms
Children Adults
Few, no constitutional symptoms Fever ( grade) (1-5d prodrome)
Headache
Malaise
Mild coryza
Conjunctivitis
Eyes
y Cataracts
y Glaucoma
y Retinitis
Heart
y Patent ductus arteriosus (PDA)
y Pulmonary artery stenosis
CNS
y Mental retardation
y Motor retardation
y Small head (microcephaly) from failed brain development
y Encephalitis
y Meningitis
Others
y Deafness
y Platelet
y Enlarged liver, spleen
y Abnormal muscle tone
y Bone disease
Investigations
Isolation of rubella virus
Rubella-specific IgM , IgG


Cytomegalovirus (CMV)
Epidemiology
Primary maternal infection 1-4% of susceptible women
Reactivation 10% of seropositive pregnant women
Transmission rate
40% after primary infection
0.2-1.8% after recurrent infection
Transmission
Urine
Saliva
Genital secretions
Transplacental
Infect placental tissue, amniotic fluid (swallowed by fetus)
Genital secretions during labour, breast milk (perinatal)
Signs & Symptoms
Petechiae
Jaundice
Microcephaly
Small size for gestational age
Investigations
Complement fixation (peak viral titers 4-7 weeks after infection)
Antigen testing
Virus isolation
Liver Function Test (LFT)
y Bilirubin
y Hepatocellular enzymes
FBP
y Thrombocytopenia
y CSF protein

CMV
Enlarged cell
Viral inclusion bodies

CMV
Owls eye
Treatment
Ganciclovir
Foscarinet


Herpes Simplex
Epidemiology
Most cases acquired during labour, delivery
Caused by HSV type 2
Risk Factors
Active genital lesion (during delivery)
Primary infection (greater risk than with recurrence)
History of genital herpes in mother, partner
Delivery through infected birth canal, LSCS
6h after rupture of membrane
Instrumental assisted delivery
Signs & Symptoms
Vesicular skin lesion
Keratoconjunctivitis, chorioretinitis
Encephalitis
Disseminated disease



Day 1

Day 17
Investigations
Isolation of virus (maternal, fetal skin lesion)
Direct immunoflourescent assay (DFA)
Serology (less useful difficult distinguish acute, past infection)
PCR of cervical fluid (detect asymptomatic women)

Hepatitis B
Immunization
HBIG (Hep B immune globulin)
Hep B vaccine

HIV
Zidovudin ( transmission rate)
Postpartum breastfeeding can transfer maternal infection to infant
Avoid obstetric intervention that breach fetal skin
Fetal scalp electrode application
Forcep delivery

Human Papiloma Virus
Causes
Genital warts
Condylomata acuminate
Laryngeal papiloma (LP) (in children) (vocal cord, epiglottis)
Cause malignant transformation of cervical cells
Cervical intraepithelial neoplasia
Cervical cancer
Transmission
Birth canal
Placenta
Investigations
Cervical scraping
Biopsy, scraping of lesions
PCR (from biopsy, scraping)
Treatment
Trichloroacetic acid in 70% ethanol

Human Parvovirus
Parvovirus B19
Causes
Erythema infectiosum (children)
Aplastic crisis (haemolytic anaemia patients)
Fetal hydrop
Fetal death

Hepatitis C
Seen in women HIV +ve
Transmission risk - maternal Hep C viral load

Pelvic Inflammatory Disease (PID)

Definition
Result of ascending infection (from endocervix) causing
y Endometritis
y Salpingitis
y Parametritis
y Oophoritis
y Tubo-ovarian abscess

Sequelae of PID
Infertility
Ectopic pregnancy
Chronic pelvic pain

Organisms
Neisseria gonorrhoea
Chlamydia trachomatis
Gardnerella vaginalis
Mycoplasma genitalium
Actinomyces israelli (IUCD)
Anaerobes

Risks
Young age (<25 y/o)
Multiple sexual partners
Past history of STI (patient, partner)
Recent sexual partner
Termination of pregnancy
IUCD insertion
Hysterosalphingography
Postpartum endometritis

Clinical Features
Lower abdominal pain
Abnormal vaginal discharge
Fever >38C
Abnormal vaginal bleeding (IMB, PCB)
Deep dyspareunia
Cervical motion tenderness (on bimanual vaginal examination)
Adnexal tenderness (on bimanual vaginal examination)



Differential Diagnosis
Ectopic pregnancy
Acute appendicitis
Endometriosis
UTI
Complication of ovarian cyst (rupture, torsion)
Irritable bowel syndrome

Investigations
Endocervical swab gonorrhoea, chlamydia
Ultrasound - identify inflamed, dilated tubes, tubo-ovarian abscess
ESR/ CRP
UPT Test exclude pregnancy

Management
Antibiotic treatment
Analgesia (pain relief)
Exclude pregnancy
Refer to sexual health clinic (genitourinary medicine)
Treatment of sexual partner
Advise to avoid sexual intercourse (until both full treated)
Offer full STI, HIV screening

Treatment
Ceftriaxone
Doxycycline
Metronidazole
Azithromycin
Followed up at 72h to check for improvement

Normal & Abnormal Puerperium

Definition
Time from delivery of placenta through 1
st
few weeks after delivery
Duration 6 weeks
Changes of pregnancy, labour, delivery have resolved
Body reverted to nonpregnant state

Physiology
Uterus
Pregnant uterus 1000g
Uterus (6w following delivery) 50-100g
Immediately postpartum, fundus palpable at level of umbilicus
Contraction of myometrium (hemostasis)
y Contraction of arterial smooth muscle
y Compression of vessels
Lochia rubra, serosa, alba
Cervix
Revert to nonpregnant state (never terutn to nulliparous state)
External os closes finger cannot be easily introduced
Vagina
Regress (not completely return to prepregnant size)
Rugae of vagina begin to reappear in women not breastfeeding
Perineum
Stretched, traumatized, torn, cut during process of labour, delivery
Muscle tone may/ may not return to normal
Abdominal Wall
Remains soft, poorly toned (for few weeks)
Return to prepregnant state (depends on maternal exercise)
Ovaries
Breastfeeding longer period of amenorrhoea, anovulation ( Prolactin)
May ovulate as early as 27d after delivery (if does not breastfeed)
Breasts
Lactogenesis initially trigged by delivery of placenta
( estrogen, progesterone)
Colostrum released during 1
st
2-4d after delivery

Postpartum Haemorrhage
Definition
Excessive blood loss during, after 3
rd
stage of labour
Average blood loss
y Vaginal delivery 500mL
y Cesarean delivery 1000mL
Postpartum Haemorrhage
Early PPH Late PPH
Occurring within 1
st
24h
after delivery
Occurs 1-2weeks after delivery
May occur up to 6w postpartum

Etiology
Early PPH Late PPH
Uterine atony
Retained prod. of conception
Uterine rupture
Uterine inversion
Placenta accrete
Lower genital tract laceration
Coagulopathy
Hematoma
Retained products of conception
Infection
Subinvolution of placental site
Coagulopathy
Factors predisposing to uterine atony
Overdistension of uterus 2 to Use of uterine-relaxing agents
Multiple gestations
Polyhydramnios
Macrosomia
Rapid, prolonged labour
Grand multiparity
Oxytocin administration
Intra-amniotic infection
Terbutaline
Magnesium sulphate
Halogenated anesthetics
Nitroglycerin
Lower genital tract laceration
Obstertical trauma operative vaginal deliveries forces, vacuum extraction
Macrosomnia
Precipitous delivery
Episiotomy
Treatment
Oxygen delivery
Bimanual massage
Removal of any blood clots from uterus
Emptying of bladder
Oxytocin infusion (routine administration)
Manual removal, uterine curettage (if retained products of conception noted)
Uterine packing
Foley catheter with a large bulb
Uterine artery embolization



Infection - Endometritis
Definition
Ascending polymicrobial infection
Causative agent normal vaginal flora, enteric bacteria
y Aerobic gram ve bacilli
y Anaerobic gram ve bacilli
y Aerobic streptococci
y Anaerobic gram +ve cocci
Etiology
Common
y Escherichia coli
y Klebsiella pneumonia
y Proteus sp.
Duration After Postpartum
1-2 days 3-4 days > 7 days Cesarean
Group A
streptococci
Enteric (E. Coli) Chlamydia
trachomatis
Anaerobic gram
ve bacilli
(Bacteroides)
Anaerobic

Risk Factors
Cesarean delivery
Young age
Socioeconomic status
Prolonged labour
Prolonged rupture of membranes
Multiple vaginal examinations
Placement of intrauterine catheter
Preexisting infection, colonization of lower genital tract
Twin delivery
Manual removal of placenta
Signs & Symptoms
Fever, chills
Lower abdominal pain
Lochia (malodorous)
Vaginal bleeding
Anorexia
Malaise
Investigations
FBC
Urinalysis
Urine culture
Blood culture
Treatment
Gentamicin
Clindamycin
Ampicillin
Vancomycin

Infection UTI
Definition
Bacterial inflammation of bladder, urethra
>10
5
colony-forming units (clean catch urine)
>10
4
colony-forming units (catheterized specimen)
Etiology
Cesarean, forceps, vacuum delivery
Tocolysis
Induction of labour
Maternal renal disease
Preeclampsia, eclampsia
Epidural anaesthesia
Bladder catheterization
Length of hospital stay
Previous UTI during pregnancy
Causative Agents
E. coli
Staphylococcus saprophyticus
E faecalis
Proteus
K pneumonia
Signs & Symptoms
Frequency
Urgency
Dysuria
Hematuria
Suprapubic, lower abdominal pain
Investigations
Urinalysis
Urine culture (clean catch, catheter)
FBC
Treatment
Trimetroprim, Sulfamethoxazole
Ciprofloxacin
Norfloxacin


Infection Mastitis
Definition
Inflammation of mammary gland
Etiology
Milk stasis, cracked nipples (influx of skin flora)
Associated with
Primiparity
Incomplete emptying of breast
Improper nursing technique
Causative organism
Staphylococcus aureus
Staphylococcus epidermidis
S saprophyticus
Streptococcus viridians
E coli
Signs & Symptoms
Fever, chills
Myalgias
Erythema
Warmth
Swelling
Breast tenderness
Treatment
Moist heat, massage, fluids, rest
Proper positioning of infant during nursing
Nursing, manual expression of milk
Analgesics
Dicloxacillin
Cephalexin
Erythromycin, clindamycin, vancomycin (if resistant to penicillin)

Infection Wound Infection
Definition
Infections of perineum developing at site of episiotomy, laceration
Infection of abdominal incision after caesarean birth
Erythema, induration, warmth, tenderness, purulent drainage
Etiology
Perineal Infections Abdominal Wound Infections
Infected lochia
Fecal contamination of wound
Poor hygiene
Diabetes
Hypertension
Obesity
Treatment with corticosteroids
Immunosuppression
Anaemia
Development of hematoma
Chorioamnionitis
Prolonged labour
Prolonged rupture of membranes
Prolonged operating time
Abdominal twin delivery
Excessive blood loss

Signs & Symptoms
Perineal Infections Abdominal Wound Infections
Pain
Malodorous discharge
Vulvar edema
Endometritis
Fever (persistent)

Treatment
Perineal Infections Abdominal Wound Infections
NSAIDs
Local anaesthetic spray
Sitz bath
Drainage, inspection of fascia



Septic Pelvic Thrombophlebitis
Definition
Venous inflammation with thrombus formation
Associated with fever (unresponsive to antibiotic)
Etiology
Bacterial infection of endometrium

Seeds organisms into venous circulation

Damage vascular endothelium
Results in thrombus formation
Risk Factors
Socioeconomic status
Cesarean birth
Prolonged rupture of membranes
Excessive blood loss
Signs & Symptoms (ovarian vein thrombosis)
Lower abdominal pain (with/ without radiation flank, groin, upper abdomen)
Nausea, vomiting
Bloating
Fever >38C
Resting tachycardia
Investigations
Urinalysis
Urine culture
FBC
CT scan, MRI
Treatment
Anticoagulation IV heparin
Gentamicin
Clindamycin
Cephalosporin (2
nd
, 3
rd
generation)
Imipenem
Cilastin
Ampicillin
Sulbactam

Postpartum Thyroiditis (PPT)
Definition
Transient destructive lymphcytic thyroiditis (1
st
year after delivery)
Etiology
Autoimmune disorder
2 Phases
Thyrotoxicosis Hypothyroidism
Occurs 1-4 months postpartum
Self-limited
Stored hormone
(result of disruption of thyroid gland)
Occurs 4-8 months postpartum
Risk Factors
+ve Antithyroid test finding
History of PPT
Family, personal history of thyroid, autoimmune disorders
Signs & Symptoms
Thyrotoxicosis Hypothyroid
Fatigue
Palpitations
Heat intolerance
Tremulousness
Nervousness
Emotional lability
Fatigue
Dry skin
Coarse hair
Cold intolerance
Depression
Memory, concentration impairment
Tachycardia
Mild exophthalmos
Painless goiter
Treatment
Thyrotoxicosis Phase Hypothyroid Phase
Beta-blocker propranolol Thyroxine (T4) replacement



Psychiatric Disorders
Definition
Postpartum blues
y Transient disorder (lasts hours to weeks)
y Characterized by bouts of crying, sadness
Postpartum Depression (PPD)
y Prolonged affective disorder (lasts weeks to months)
Postpartum Psychosis
y 1
st
postpartum year
Etiology
Multifactorial
Stress of peripartum period
Responsibilities of child rearing
Endorphins of labour, Estrogen, progesterone after delivery
Tryptophan
Risk Factors
Undesired pregnancy
Feeling unloved by mate
Age < 20 y/o
Unmarried status
Medical indigence
Self esteem
Dissatisfaction with extent of education
Economic problems housing, income
Poor relationship husband, boyfriend
Being part of a family with 6 siblings
Limited parental support child, adult
Past, present emotional problems
Signs & Symptoms
Postpartum Blues PPD Postpartum Psychosis
Bouts of sadness
Crying
Anxiety
Irritation
Restlessness
Mood lability
Headache
Confusion
Forgetfulness
Insomnia
Insomnia
Lethargy
Libido
Appetite
Pessimism
Incapacity for love
Feelings of inadequacy
Ambivalence
-ve feelings to infant
Inability to cope
Schizophrenia
Manic depression

Treatment
Postpartum Blues PPD Postpartum Psychosis
Education Supportive care
SSRIs
Electroconvulsive
Psychiatrist



Cervical Neoplasia

Malaysian National Cancer Registry (2003-2005)
Cervical cancer is 10.6% of total female cancers
Age standardized rate 16.1/100,000
y Chinese ASR 23.2/100,000
y Indians ASR 16.4/100,000
y Malays ASR 8.7/100,000
Peak incidence 60-69 y/o

Cervix Uteri (Peninsular Malaysia 2003-2005)


Anatomy, Histology


Transformation zone
(abrupt transition)
(cervical cancer)
Endocervix Ectocervix Vagina
Columnar cells Squamous cells
Non-keratinized
Squamous cells
Keratinized


Risk for Cervical Cancer
Indulge in sexual activity at early age
Many sex partners, spouse have many sex partners
Sexual intercourse with men who had early age at 1
st
sexual intercourse
Sexual intercourse with males who had wives/ sex partners died of cervical ca
STDs, sexual intercourse with male who have STD
Smoke, spouse who smoke

Genital HPV Types & Outcomes (Human Papillomavirus)
HPV Type Clinical Findings Cancer Potential
6, 11 Genital warts
Low grade lesions
Recurrent respiratory papillomatosis (RRP)
Negligible
40, 42, 43,
44, 54, 61,
70, 72, 81,
CP6108
Low grade lesions Negligible
16, 18, 31,
33, 35, 39,
45, 51, 52,
56, 58, 59,
68, 73, 82
Low grade lesions
High grade lesions
Cancer
High



Pathogenesis
Transformational zone cells
Sexual intercourse
Squamous metaplasia

HPV exposure
(E6, E7)

Infected basal cells

Productive infection Integrated HPV Persistent infection

Activate oncogenes
N-myc, C-myc
Inactivation of tumour
suppressor genes
(cofactors)
P53
Rb

Invasive cancer

HPV acts as initiator of oncogenesis
Needs interaction with somatic, environmental factor to cause cancer
Cofactors
Smoking
Immune status
Dietary habits
Socioeconomic status
Hormones
Individual susceptibility
Viral load
Genital infections


Steps in HPV Induced Cervical Cancer


Terminology
Metaplasia
Dysplasia mild, moderate, severe
Neoplasia CIN I, CIN II, CIN III
LSIL CIN I, HPV infection
HSIL CIN II, CIN III
Carcinoma in situ (CIS)
Cancer/ carcinoma
CIN Cervical intraepithelial neoplasia
LGIL Low grade intraepithelial lesion
HGIL High grade intraepithelial lesion
CIN III = CIS


Histology

Normal

Metaplasia

Koilocytes (metaplastic squamous)
Nuclei immature
Large
Perinuclear halo
Dense cytoplasm

Dysplasia (CIN III)

CIN I 1/3
CIN II 2/3
CIN III whole thickness

< 5 mm microinvasion
> 5 mm cervical cancer
Normal


HPV


CIN II


CIN III

CIS with microinvasion


Morphology

Ulcerative(Endophytic growth)
Irregular ulcer
Margin everted
Raised

Cancerous Cervix (Exophytic growth)
Cauliflower-like growth
Fungating growth
Necrotizing, haemorrhage
Friable

Normal Cervix

Abnormal Cervix (precursor lesion)
Persistent HPV infection

Clinical Features
Asymptomatic CIN changes (3
rd
decade)
Cancer peak 5
th
decade
Irregular vaginal bleeding
Leucorrhea
Dysparenea
Dysuria
Symptoms of local spread

Classification
Gross Histology
Exophytic (fungating)
Endophytic/ ulcerative
Infiltrative
Large cell non-keratinising (65%)
Large cell keratinising (25%)
Small undifferentiated squamous cell
Adenocarcinoma

Cervical cancer

Squamous cell carcinoma
Large cells
Abundant pink cytoplasm
Contain keratin
Nuclear vesicular
Extracellular keratin pearls
Lymphocytes

Cervical cancer

Adenocarcinoma
Long, tubular gland
Tall columnar cells
Nuclear : Cytoplasm ratio
Vesicular nucleoli
Mucin secretion


Spread
Direct
Uterus, bladder, ureters, rectum, vagina
Lymphatics
1
st
Station 2
nd
Station
Paracervical lymph node
Hypogastric lymph node
Obturator lymph node
External iliac lymph node
Sacral lymph node
Common iliac node
Aortic lymph node
Inguinal lymph node
Blood
Lungs, liver, BM

FIGO Classification
0 Carcinoma in situ (CIN III)
I Confined to cervix
II Extend beyond cervix, upper 1/3 vagina
III Extend to pelvic wall, lower 1/3 vagina
IV Extend beyond true pelvis, distant metastasis

Prognosis depend on
Clinical stage
Nodal status
Tumour size
Depth of invasion
Parametrial involvement
Endometrial extension
Blood vessel invasion
Microscopic grading, type
Cell proliferative indices angiogenesis

5 Year Survival Rate
0 100%
I 80-90%
II 75%
III 35%
IV 10-15%

HPV Vaccination
Gardasil (HPV 6, 11, 16, 18)
Cervarix (HPV 16, 18)
Indication
Young girls before onset of sexual intercourse


Pap Smear
Site of sampling transformation zone
When not to take samples
During menses
Few days before menses
Advantages
Detect treatable precursor lesions (dysplasia/ CIS, CIN, SIL)
Not suitable for screening adenocarcinoma (common uterine carcinoma)
Reduction in cervical cancer
10 years done once 30%
5 years done once 80%
3 years done once 90%
2 years done once 91%
1 year done once 93%
Recommended
3 year once
Ideally
Adequate sampling
Optimum timing
Optimum preservation


Wooden Ayer Spatula


Cytobrush

Cbstetr|cs n|story 1ak|ng
at|ent Ident|f|cat|on
name
Age years old
LLhnlc
Sex lemale
CccupaLlon
Address
uaLe of admlsslon
uaLe of clerklng
lnformanL
Cravlda
ara
AborLlon
LM resenL as CA
8Luu (8evlsed Luu) (u/S) resenL as CC
Luu LM + 7d 3mLh + 1yr
CA CounL from LM
resenL as weeks days
1 mLh 4w + 2d
2 mLh 8w + 3d
3 mLh 12w + 1w
Ch|ef Comp|a|n (complaln + duraLlon)
n|story of resent|ng I||ness (nCI)
ls paLlenL ln labour?
Showblood sLalned mucus passed v | Leaklng llquor | ConLracLlon paln (regular)
lf sympLoms presenL leLal movemenL | WhaL ls done ln hosplLal?
n|story of resented regnancy (nC)
SuspecL pregnancy Why? Mlssed perlod
Culckenlng
Abdomlnal dlsLenLlon
When?
Conflrm pregnancy When?
Where?
Who?
8ooklng When? (8ed Card)
(1sL anLenaLal checkup) Where?
PelghL cm
WelghL kg
8 mmPg
lundal helghL cm
8lood group (8h)
Pb
urlne glucose
urlne proLeln
vu8L 8eacLlve/ non8eacLlve
SubsequenL ALLend all AnC follow schedule?
anLenaLal checkup (AnC) MonLhly Llll 28w
lorLnlghLly Llll 36w
Weekly Llll dellvery
normal parameLers? WelghL galn
8
uLerlne slze
Pb
urlne glucose proLeln
ulLrasound done? When?
1114w for correcL daLlng AbnormallLles? (sLaLe)
2024w Lo deLecL congenlLal abnormallLles
Culckenlng When?
(1sL feLal movemenL) lnLenslLy lrequency?
rlmagravlda 1820w (3mLh)
MulLlgravlda 1618w (4mLh)
Slgns SympLoms nausea vomlLlng
of regnancy 8reasL dlscomforL/ engorgemenL
lrequency
ConsLlpaLlon
Ankle edema
8ackache
lmmunlzaLlon AnLlLeLanus Loxold (A11)
PepaLlLls 8 (3x)
8ubella (usually ln school)
ast Cbstetr|c n|story (Cn) (noL requlred lf prlmlgravlda)
MarlLal sLaLus When marrled?
Marrled aL age?
1sL marrled? 1he only marrled?
Consangulneous marrled?
no of chlldren boys glrls
lor Lach regnancy (14 chlldren)
Age
Sex
Where dellver?
When? lull Lerm? CC lf preLerm?
MeLhod of dellvery
8lrLh welghL (normal 334kg)
CompllcaLlons (anLeparLum lnLraparLum posLparLum)
8reasLfeed Llll? (normal 2yr lf early/ boLLle feedlng why?)
lf all dellverles are normal summarlze no A l Cx (aL end of presenLaLlon of CP)
AborLlon CC?
(how many?) Why?
Slgns sympLoms before aborLlon
ullaLaLlon cureLLage (uC) done?
uC lncompleLe aborLlon | no uC compleLe aborLlon
lor Lach regnancy (lf 3 chlldren)
Any unevenLful dellverles? l1Svu wlLh no Cx
Age of eldesL chlld
Age of youngesL chlld
8lrLh welghL (range)
8reasLfeedlng
MenLlon abnormal dellverles separaLely
Spaclng Cood ( 2 years aparL)
Abnormal ( 6 years)
Why? ConLracepLlon? SubferLlllLy?
ConLracepLlve MeLhod CC/ ln[ecLlon/ lmplanLaLlon
(?es? no?) luuC
Condom
CLhers
Menstrua| n|story
Menarche (1sL mensLrual) years old normal 916 y/o
MensLrual cycle 8egular/ lrregular
Cycle normal 2133d
llow normal 28d
Peavy flow normal 1sL3rd day
ad used (volume) normal 30ml
ast Gynaeco|ogy n|story
roblems uysmenorrhoea (palnful)
Menorrhagla (prolonged lncreased 80ml)
lnLermensLrual bleedlng
osLcolLal bleedlng
uyspareunla (palnful colLal)
ap smear Pow many Llmes?
When was lasL one?
8esulL normal?
ast Med|ca| Surg|ca| n|story
PlsLory of Chronlc lllness PyperLenslon
uM
PearL dlsease
AsLhma
18
Any surgery?
Iam||y n|story
ersona| Soc|a| n|story
LducaLlon level
Pusbands age occupaLlon lncome
Pouse condlLlon
Pow frequenL husband vlslL?
Who Lake care of chlldren durlng admlsslon?
Pow does she conLacL her chlldren?
Smoke/ Alcohol? (paLlenL husband)
Drug n|story
lron
lolaLe
vlLamln 812 C
CvercounLer drugs
1radlLlonal med
Allergy
D|etary
AdulL dleL
Allergy
lf dlabeLlc deLalls requlred dlshes for every meals
Summary
Age Cravlda ara CA Chlef Complaln
System|c kev|ew
8esplraLory SC8
nlghL sweaL
lever
Cough
PaemopLysls
CvS PyperLenslon
Ankle swelllng
ChesL paln
alplLaLlon
MusculoskeleLal Muscle paln [olnL paln
ueformlLy
Muscle wasLlng
CnS LCC
aralysls
1remor
urowslness
Peadache
Cl1 LCW
LCA
Abdomlnal paln
aln ln swallowlng
vomlLlng
nausea
PemaLemesls
ularrhoea
ConsLlpaLlon
Lndocrlne Swelllng ln neck
ulabeLes melllLus
Ovarian Tumours

Normal Histology


Classification
Surface Epithelial
Cell
Germ Cell Sex Cord-Stroma
Metastasis to
ovary
70% frequency 20% frequency 10% frequency 5% frequency
> 20 y/o 0-25 y/o All ages Varies
Serous tumor
Mucinous tumor
Endometriod tm.
Clear cell tumor
Brenner tumor
Cystadenofibroma
Teratoma
Dysgerminoma
Endodermal sinus
(yolk sac tumor)
Choriocarcinoma
Fibroma
Granulosa-Theca
cell tumor
Sertoli-Leydig cell
tumor


Etiology
Risk Risk
Nulliparity
Early menarche
Late menopause
Estimated no. of years of ovulation
Unmarried, married with low parity
Family history BRCA 1, BRCA 2
Genetic mutations sporadic
(HER2/ NEU, K-RAS, p53)
Oral contraceptive
Age at 1
st
birth

Incessant Ovulation Theory
Ovulation rupture surface epithelium

Repair by proliferation (DNA synthesis)

Successive bouts of trauma (rupture)
Repair induce genetic instability

Mutation risk

Epithelial tumours

Clinical Features
Asymptomatic
y Until well advanced
y Found accidentally during investigation of unrelated problems, check up
Abdominal swelling (when tumour is large)
Pain (from torsion, rupture, haemorrhage, infection)
Pressure effect (constipation, urinary incontinence, frequency)
Menstrual disturbances
Hormonal effects (sex cord tumour estrogen effect)
Abnormal cervical smear
Constitutional symptoms for cancer
y Appetite
y Weight
y Cachexia



Approach
History Physical Examination
Gynaecology history
LMP
Menstrual cycle
Previous pregnancies
Contraception
Drug, family history
Systemic review metastatic tumour
Lymph node palpation
Abdominal examination
Bimanual palpation
(nodules in pouch of Douglas)
(tenderness)

Investigations
Ultrasound
X-ray
y Chest (metastasis)
y Abdomen (calcification benign teratoma)
CT-PET scan (assist staging)
Blood test
y Infection (WBC)
y Platelet (haemorrhage)
Hormonal level estrogen
y Physiological follicular cyst
y Sex cord stromal tumour
CA-125 (serous, endometroid carcinoma)
-fetoprotein (endodermal sinus (yolk sac) tumour)
Inhibin (granulose cell tumour)
-HCG (dysgerminoma)

FIGO Staging (Laparotomy)
1. Growth limited to ovaries
2. Growth involving 1 ovaries with pelvic extension
3. Growth involving 1 ovaries with peritoneal implants outside pelvis
+ve retroperitoneal/ inguinal lymph node
Superficial liver metastasis = stage 3
4. Growth involving 1 ovaries with distance metastasis
If pleural effusion, +ve cytology = stage 4
Parenchymal liver metastasis = stage 4

Management
Surgery Chemotherapy
Primary therapy (Diagnose, treat)
y Total abdominal hysterectomy &
bilateral salpingo-oophorectomy
y Omentectomy
y Conservative primary surgery
(unilateral salpingo-
oophorectomy)
Adjuvant therapy
Indication
Stage Ic and above
Type
y Clear cell carcinoma
y Serous papillary
cystadenocarcinoma
Type of drug
Epithelial Non-Epithelial
Carboplatin BEP
Bleomycin
Etoposide
Cisplatin
Cisplatin
Paclitaxel

Young, nulliparous women with stage
Ia disease
No synchronous endometrial tumour

Benign Ovarian Tumour

Epidemiology
Young women Older women
Germ cell tumour Surface epithelial cell tumour

Pathology
Physiological cyst
Follicular cyst
Luteal cyst
Benign surface epithelial tumour
Serous cystadenoma
Mucinous cystadenoma
Endometroid cystadenoma
Brenner tumour
Clear cell tumour
Benign germ cell tumour
Dermoid cyst (mature cystic teratoma)
Mature solid teratoma
Benign sex cord stromal tumour
Sex cord stromal tumour
Granulosa cell tumour
Theca cell tumour
Fibroma
Sertoli-Leydig cell tumour

Mature Teratoma (Dermoid Cyst)
Unilateral (80%)
Enlarged (< 10cm in diameter)


No stratification
No stromal invasion




Other Benign Surface Epithelial Tumours
Endometroid
Tumor
Clear cell/
Mesonephroid
Tumor
Brenner/
Transitional
Epithelial Tumor
Cystadeno-
fibroma
Tubular glands
formation
Cystic neoplasm
Polypod masses
Protrude in cyst
Solid nests of
transitional
(urothelium) like
cells
Resemble lining
of urinary tract
Proliferation of
fibrous stroma
Multinodular
tumor
Chocolate
(fill linings of
cystic spaces)
Clear cytoplasm
Small
Multilocular
Simple papillary
processes
Encased in dense
fibrous stroma

Other Benign Tumours




Serous Cystadenoma, Mucinous Cystadenoma
Serous Cystadenoma Mucinous Cystadenoma




Malignant Ovarian Tumour

Serous Carcinoma (Serous Cystadenocarcinoma) , Mucinous Carcinoma (Mucinous Cystadenocarcinoma)
Serous Carcinoma (Serous Cystadenocarcinoma) Mucinous Carcinoma (Mucinous Cystadenocarcinoma)
Most common (40% of all malignant ovarian tumours)
45 65 y/o
Secrete serous fluid
10% of all malignant ovarian tumours
Middle adult life (rare - before puberty, after menopause)
Secrete mucinous fluid

Serous Cystadenocarcinoma
Bilateral (usually)
Solid (haemorrhage, necrosis), cystic (large cysts divided by septa multilocular)
Nodular irregularities (papillary projections)

Mucinous Cystadenocarcinoma
Unilateral (usually)
Larger, Multilocular
Thin-walled cysts with a smooth external surface
Mucinous fluid (sticky, gelatinous fluid, rich in glycoproteins)
Papillation
Serosal penetration (invasion)
Solidified areas


Other Malignant Tumours
Endometroid Carcinoma Clear Cell Carcinoma (mesonephroid) Brenner Tumour Immature Teratoma
Resemble endometrial carcinoma
Cystic
Unilocular
Turbid brown fluid
Resemble endometrial epithelial lining
(tubular glands)
Least common Uncommon (only some is malignant) Rare
Coexist with other germ cell
(eg. Choriocarcinoma)
Prepubertal adolescent, young women
18 y/o (mean age)
Clear cell pattern
(abundant clear cytoplasm)
Tubulo-cystic pattern
Hob-nail appearance
Solid
Unilateral
Transitional-like epithelium
(resemble urinary tract)
Resemble fetus/ embryo tissue
(rather than adult)
Gross
Solid
Smooth external surface
Areas of haemorrhage, necrosis
Hair
Cartilage
Grumous material
Histology
Immature tissues
(cartilage, bone, glands)
Immature neuroepithelium

Pathology of Uterus

Pathology
Endometrium Myometrium
Epithelium
Stroma (benign, malignant)
Leiomyoma
Leiomyosarcoma
Adenomyosis
Adenomyoma

Normal Endometrium
Proliferative Phase Secretory Phase
Tall columnar epithelium
Frequent mitotic activity
Tubular glands
Cellular stroma
Tortuous glands
Cuboidal cells
Subnuclear vacoulation
Edematous stroma



Stimulation
Estrogen Progesterone
Stimulate gland (labile cells) Stimulate stroma (stable cells)

Atypia
Nuclear : Cytoplasmic ratio
Hyperchromatism of nucleus
Mitotic activity
Lose polarity

Signs & Symptoms
Abnormal uterine bleeding
Massive per vaginal bleeding
Size of uterus
If menopause, obese likely carcinoma
If perimenopause hyperplasia
If young fibroid, stromal tumour


Menstrual Disorders (DUB Dysfunctional Uterine Bleeding)
Anovulatory cycle (Prolonged estrogen stimulation)
y Causes Endocrine disorder (eg. Diabetes Mellitus)
y Primary ovarian disease
y Generalized metabolic disturbance
(eg. Severe obesity, malnutrition)
Inadequate luteal phase
OCP induced endometrial changes

Endometrial Hyperplasia
Occur after/ around menopause
Cause
Estrogen (abnormal)
Absent progestational activity
Endometrial cancer risk
Risk parallel to degree of atypia
Hyperplasia without atypia 2% risk
Hyperplasia with atypia 23% risk

Pathology
Simple Hyperplasia
without atypia
Complex Hyperplasia
(adenomatous
hyperplasia)
Atypical Hyperplasia
(adenomatous
hyperplasia with
atypia)
Cystic/mild
hyperplasia
Stoma cellular
Mitosis scanty
Rarely progress to ca
Loss of polarity
Complex glands
Altered N:C ratio
Mitoses

Morphology

Normal

Cystic Glandular Hyperplasia

Adenomatous Hyperplasia
without atypia

Adenomatous Hyperplasia
with atypia

Endometrial Hyperplasia
Thickened endometrium

Endometrial Hyperplasia
Cystic glandular hyperplasia

Endometrial Hyperplasia with atypia
Back-to-back configuration
Intraluminal papillary infolding into gland
Tall, columnar, basophilic


Endometrial Carcinoma
Uncommon < 40 y/o
Risk factors
Obesity
Diabetes
Hypertension
Infertility
Single, nulliparous
History of anovulatory cycles
Breast cancer

Endometrial carcinoma
Fungating, friable
Infiltrating myometrium
Size of uterus

Endometrial carcinoma (Invade myometrium)
Endometrial gland (labile cells)
Atypical
Infiltrative
Investigations
Pap smear (not helpful)
Ultrasound vaginal, abdominal
Endometrial curettage
Pippelle sampling

Endometrial Stromal Tumour
Types
Benign Malignant
Endometrial stromal nodule Endometrial stromal sarcoma
Mean age 30 y/o Mean age 60 y/o
Very rare
Histopathology diagnosis
Abnormal uterine bleeding

Endometrial Stromal Tumour


Leiomyoma
Most common benign tumours of uterus

Leiomyoma
Non-encapsulated
Whorl appearance

Leiomyoma

Leiomyosarcoma

Adenomyosis

Adenomyosis

Adenomyosis

Physiology of Menopause

Staging System

Not applied in
Cigarette smokers
BMI < 18, BMI > 30
Heavy aerobic exercise
Chronic menstrual cycle irregularity
Hysterectomy
Abnormal uterine (fibroids), ovarian (endometrioma) anatomy

Definition
Menopause
After 12 months of amenorrhoea
FMP (retrospective diagnosis)
Near complete but natural ovarian hormone secretion
Perimenopause (Climacteric)
Around the menopause
Begin same time as MT (menopausal transition) (stage -2)
Ends 12 months after FMP

Age at Menopause
51 y/o (median age at natural menopause)
Experience menopause
Earlier Later
Africans
African-Americans
Hispanics of Mexican
Caucasian
Japanese
Malaysian


Etiologic Factors for Early Menopause
Race, ethnicity (Latin America > Japanese, Europe, North America)
Parity (nulliparous > multiparous)
No prior OCP use
Socioeconomic status
y Education, unemployed
y Marital status single > married
Familial, genetic factors
Environmental toxins
y Smoking
y Chemotherapy
y Irradiation
y Galactose consumption
BMI > 30, physical activity
Depression, anxiety
Surgical trauma to ovarian blood supply oophorectomy, hysterectomy

Physiological Basis of Menopause
Oocyte depletion in ovary
Reproductive aging
Steady loss of occytes atresia, ovulation
Does not necessarily occur at constant rate
Relatively wide age range
45-55 y/o
Variation number of follicles at birth, rate of occyte loss




Hormone Level Changes




Hormonal Changes in Menopausal Transition (MT)
Ovarian Inhibin Factor

FSH

E2 production (early stage of MT)

E2 (several years of final menstrual period)
Favour greater output of FSH (in absence of any changes in E2 production)
Inhibin B (early MT)
Inhibin A (luteal phase)
Activin A (MT stage)



Symptoms of Menopausal Transition (MT)
Irregular cycle
Vasomotor symptoms Hot flashes
Breast tenderness
Insomnia
Migraines
Premenstrual dysphoria (sadness)
Genital atrophic symptoms
Sexual function problems

Hot Flashes
Frequent in stages -1 and +1
Transient periods of intense heat upper arms, face
Flushing of skin, profuse sweating
Accompanied with
y Chills
y Palpitations
y Anxiety
Causes
Changes in core body temperature
Changes in endogenous hormone levels
Estrogen

Downward shift of temperature set point occurs intermittently

Misperception that body is warmer than it should be

Body disperses heat

Warm sensation

Estrogen

LH pulses

Vasodilatory effects
Consequences
Sleep disturbances
Fatigue
Irritability
Forgetfulness
Acute physical discomfort
-ve effects on work

Atrophy of Estrogen Dependent Tissues
Breast sags
Vagina thin, atrophic
Vulva thin, atrophic
Trigone of bladder atrophies
General skin atrophy
Pelvic floor support

Genital Changes
Vaginal atrophy, dryness
Vascularity
Estrogen - glycogen of vaginal epithelial - lactobacilli - pH
(overgrowth of coliforms, streptococci)
Associated symptoms
y Itching
y Burning
y Discomfort
y Vaginal bleeding
Uterine prolapse
Cardinal, uterosacral ligaments lose tonicity (support the uterus)
Cystocele, rectocele
Elastic tissue around vagina
Urethra support

Lower Urinary Tract Changes
Estrogen receptors located on urethra, bladder trigone
After menopause, urethra become thinner
(due to regression of squamous epithelial layer)
Dysuria (thinned urethra)
Frequency (atrophic trigonitis)
Stress incontinence (less sphincter tone)
Urge incontinence (atrophic trigonitis)


Psychological Changes
Depression
Tiredness
Irritability
Energy
Memory
Concentration
Libido
Anxiety

Skin, Joint Symptoms
Thin, dry skin
Brittle nails
Loss of hair
Aches, pains
Due to
Loss of tissue collagen
30% of skin collagen is lost within 5 years

Long Term Problems
Osteoporosis
Coronary heart disease
Alzheimer disease
Osteoporosis
Bone mass - Fractures
Fracture of spine, hip, wrist
Osteoclast, osteoblast cells estrogen receptors (promote bone remodelling)
Factors Bone Loss
Nutrition alcohol, caffeine, Ca2+/ vitamin D
Body weight thin
Lifestyle inactivity, smoking, bed rest
Genetic family history, female, race
Sex hormone status premature menopause, postmenopausal
Diseases Cushings syndrome, Hyperthyroidism, Diabetes mellitus
Drugs steroids, thyroxine
Estrogen protection against osteoporosis
Sensitivity of bone to PTH (without change amount of circulatory PTH)
Calcitonin
Ca2+ absorption in intestine
Coronary Heart Disease
Estrogen protection against cardiovascular disease
y LDL
y HDL
Direct protective effect of estrogen upon arterial wall
y atherosclerotic plaques
y Direct vasodilatation effects
Alzheimer Disease
Estrogen

Synapses, neuronal growth

-amyloid in Alzheimer

Action of Ca2+ Regulatory Hormones
Bone Kidney GIT
PTH Bone resorption
(Ca2+, PO4-)
Ca2+, PO4-
reabsorption
No direct effect
Vitamin D Bone resorption
(PTH presence)
Ca2+, PO4-
reabsorption
Ca2+, PO4-
reabsorption
Calcitonin Bone resorption Ca2+, PO4-
reabsorption
No direct effect