The Physiology ofThe Physiology of

Pregnancy, Parturition and Pregnancy, Parturition and LactationLactation

M. Djauhari WidjajakusumahM. Djauhari Widjajakusumah

Fakultas Kedokteran Universitas IndonesiaFakultas Kedokteran Universitas Indonesia

The Physiology ofThe Physiology of

Pregnancy, Parturition and Pregnancy, Parturition and LactationLactation

M. Djauhari WidjajakusumahM. Djauhari Widjajakusumah

Fakultas Kedokteran Universitas IndonesiaFakultas Kedokteran Universitas Indonesia

PregnancyPregnancyPregnancyPregnancy

CLEAVAGE CLEAVAGE AND AND

IMPLANTATIIMPLANTATIONON

human Chorionic Gonadotropin (hCG)human Chorionic Gonadotropin (hCG) human Chorionic Gonadotropin (hCG)human Chorionic Gonadotropin (hCG)

• Produced by syncytiotrophoblastProduced by syncytiotrophoblast

• hCG-hCG-αα is identical to is identical to αα subunit LH, FSH and TSH subunit LH, FSH and TSH

• Is primarily luteinizing and luteotropic, little FSH activityIs primarily luteinizing and luteotropic, little FSH activity

• Detected in the urine as early as 14 days after conceptionDetected in the urine as early as 14 days after conception

• Acts on the same receptor as LHActs on the same receptor as LH

• Produced by syncytiotrophoblastProduced by syncytiotrophoblast

• hCG-hCG-αα is identical to is identical to αα subunit LH, FSH and TSH subunit LH, FSH and TSH

• Is primarily luteinizing and luteotropic, little FSH activityIs primarily luteinizing and luteotropic, little FSH activity

• Detected in the urine as early as 14 days after conceptionDetected in the urine as early as 14 days after conception

• Acts on the same receptor as LHActs on the same receptor as LH

Other Placental HormonesOther Placental HormonesOther Placental HormonesOther Placental Hormones

• human Chorionic Somatomammotropin (hCS)human Chorionic Somatomammotropin (hCS)

Produced by syncytiotrophoblast Produced by syncytiotrophoblast Large amount of human placental lactogen / hPL Large amount of human placental lactogen / hPL

(lactogenic activity) (lactogenic activity)

Small amount of chorionic growth hormone-prolactin Small amount of chorionic growth hormone-prolactin /CGP (growth-stimulating activity)/CGP (growth-stimulating activity)

o large quantities in maternal blood, very little reaches large quantities in maternal blood, very little reaches the fetusthe fetus

o functions as “maternal growth hormone of pregnancy”functions as “maternal growth hormone of pregnancy”o hCS levels are proportionate to the size of placenta hCS levels are proportionate to the size of placenta

low hCS levels are sign of placental insufficiency low hCS levels are sign of placental insufficiency

• human Chorionic Somatomammotropin (hCS)human Chorionic Somatomammotropin (hCS)

Produced by syncytiotrophoblast Produced by syncytiotrophoblast Large amount of human placental lactogen / hPL Large amount of human placental lactogen / hPL

(lactogenic activity) (lactogenic activity)

Small amount of chorionic growth hormone-prolactin Small amount of chorionic growth hormone-prolactin /CGP (growth-stimulating activity)/CGP (growth-stimulating activity)

o large quantities in maternal blood, very little reaches large quantities in maternal blood, very little reaches the fetusthe fetus

o functions as “maternal growth hormone of pregnancy”functions as “maternal growth hormone of pregnancy”o hCS levels are proportionate to the size of placenta hCS levels are proportionate to the size of placenta

low hCS levels are sign of placental insufficiency low hCS levels are sign of placental insufficiency

Other Placental HormonesOther Placental HormonesOther Placental HormonesOther Placental Hormones

• RelaxinRelaxin

Produced by placenta, uterus, corpus luteum, Produced by placenta, uterus, corpus luteum, mammary glands, prostate glandmammary glands, prostate gland

Relaxes the pubic symphysis, pelvic jointsRelaxes the pubic symphysis, pelvic joints

Softens and dilates the uterine cervix Softens and dilates the uterine cervix facilitates deliveryfacilitates delivery

• RelaxinRelaxin

Produced by placenta, uterus, corpus luteum, Produced by placenta, uterus, corpus luteum, mammary glands, prostate glandmammary glands, prostate gland

Relaxes the pubic symphysis, pelvic jointsRelaxes the pubic symphysis, pelvic joints

Softens and dilates the uterine cervix Softens and dilates the uterine cervix facilitates deliveryfacilitates delivery

Hormone levels in human maternal Hormone levels in human maternal blood blood

during normal pregnancyduring normal pregnancy

Hormone levels in human maternal Hormone levels in human maternal blood blood

during normal pregnancyduring normal pregnancy

HormoneHormone Time of Peak SecretionTime of Peak Secretion

hCGhCG First trimesterFirst trimester

RelaxinRelaxin First trimesterFirst trimester

hCShCS TermTerm

Estradiol Estradiol TermTerm

Estriol Estriol TermTerm

Progesterone Progesterone TermTerm

Prolactin Prolactin TermTerm

HormoneHormone Time of Peak SecretionTime of Peak Secretion

hCGhCG First trimesterFirst trimester

RelaxinRelaxin First trimesterFirst trimester

hCShCS TermTerm

Estradiol Estradiol TermTerm

Estriol Estriol TermTerm

Progesterone Progesterone TermTerm

Prolactin Prolactin TermTerm

Parturition Parturition Parturition Parturition

ParturitionParturitionParturitionParturition

• Estrogens increase the number of oxytocin receptors in Estrogens increase the number of oxytocin receptors in myometrium > 100 x during pregnancymyometrium > 100 x during pregnancy

• Reaches its peak during early laborReaches its peak during early labor

• Uterine distention late in pregnancy may also increase the Uterine distention late in pregnancy may also increase the number of oxytocin receptorsnumber of oxytocin receptors

• Increased number of oxytocin receptors causes uterus to Increased number of oxytocin receptors causes uterus to respond to normal plasma oxytocin concentration in the early respond to normal plasma oxytocin concentration in the early labor stagelabor stage

• Estrogens increase the number of oxytocin receptors in Estrogens increase the number of oxytocin receptors in myometrium > 100 x during pregnancymyometrium > 100 x during pregnancy

• Reaches its peak during early laborReaches its peak during early labor

• Uterine distention late in pregnancy may also increase the Uterine distention late in pregnancy may also increase the number of oxytocin receptorsnumber of oxytocin receptors

• Increased number of oxytocin receptors causes uterus to Increased number of oxytocin receptors causes uterus to respond to normal plasma oxytocin concentration in the early respond to normal plasma oxytocin concentration in the early labor stagelabor stage

Parturition Parturition Parturition Parturition

Estrogens Estrogens Increased oxytocin receptors Increased oxytocin receptors Uterine distention Uterine distention

Prostaglandin Prostaglandin

Uterine contractionsUterine contractions

Dilatation of cervix and distention of vaginaDilatation of cervix and distention of vagina

Stimuli from cervix and vaginaStimuli from cervix and vagina

Increased secretion of oxytocinIncreased secretion of oxytocin

Estrogens Estrogens Increased oxytocin receptors Increased oxytocin receptors Uterine distention Uterine distention

Prostaglandin Prostaglandin

Uterine contractionsUterine contractions

Dilatation of cervix and distention of vaginaDilatation of cervix and distention of vagina

Stimuli from cervix and vaginaStimuli from cervix and vagina

Increased secretion of oxytocinIncreased secretion of oxytocin

Parturition Parturition Parturition Parturition

Oxytocin increases unterine contractions in two ways:Oxytocin increases unterine contractions in two ways:

1.1. Acts directly on myometrium, uterine smooth muscles Acts directly on myometrium, uterine smooth muscles contractcontract

2.2. Stimulates prostaglandins formation in the decidua. Stimulates prostaglandins formation in the decidua. Prostaglandins enhance the oxytocin-induced contractionsProstaglandins enhance the oxytocin-induced contractions

Spinal reflexes and voluntary contractions of abdominal Spinal reflexes and voluntary contractions of abdominal muscles also aid in deliverymuscles also aid in delivery

Oxytocin increases unterine contractions in two ways:Oxytocin increases unterine contractions in two ways:

1.1. Acts directly on myometrium, uterine smooth muscles Acts directly on myometrium, uterine smooth muscles contractcontract

2.2. Stimulates prostaglandins formation in the decidua. Stimulates prostaglandins formation in the decidua. Prostaglandins enhance the oxytocin-induced contractionsProstaglandins enhance the oxytocin-induced contractions

Spinal reflexes and voluntary contractions of abdominal Spinal reflexes and voluntary contractions of abdominal muscles also aid in deliverymuscles also aid in delivery

STAGES OF STAGES OF LABORLABOR

Mammary Gland and Mammary Gland and LactationLactation

Mammary Gland and Mammary Gland and LactationLactation

Development of The BreastsDevelopment of The BreastsDevelopment of The BreastsDevelopment of The Breasts

• Estrogens are primarily responsible for proliferation of mammary ductsEstrogens are primarily responsible for proliferation of mammary ducts

• Progesterone are primarily responsible for the development of the Progesterone are primarily responsible for the development of the lobuleslobules

• Prolactin in humans may also be needed for mammary glands Prolactin in humans may also be needed for mammary glands development at pubertydevelopment at puberty

• Increased prolactin levels, and high levels of estrogens and Increased prolactin levels, and high levels of estrogens and progesterone (and possibly hCG) cause full breast lobulo-alveolar progesterone (and possibly hCG) cause full breast lobulo-alveolar development during pregnancydevelopment during pregnancy

• Cortisol, insulin, and growth hormone are necessary for mammary Cortisol, insulin, and growth hormone are necessary for mammary developmentdevelopment

• Estrogens are primarily responsible for proliferation of mammary ductsEstrogens are primarily responsible for proliferation of mammary ducts

• Progesterone are primarily responsible for the development of the Progesterone are primarily responsible for the development of the lobuleslobules

• Prolactin in humans may also be needed for mammary glands Prolactin in humans may also be needed for mammary glands development at pubertydevelopment at puberty

• Increased prolactin levels, and high levels of estrogens and Increased prolactin levels, and high levels of estrogens and progesterone (and possibly hCG) cause full breast lobulo-alveolar progesterone (and possibly hCG) cause full breast lobulo-alveolar development during pregnancydevelopment during pregnancy

• Cortisol, insulin, and growth hormone are necessary for mammary Cortisol, insulin, and growth hormone are necessary for mammary developmentdevelopment

MAMMARY MAMMARY GLANDGLAND

MAMMARY GLANDMAMMARY GLAND

Lactation – Secretion and Ejection of Lactation – Secretion and Ejection of MilkMilk

Lactation – Secretion and Ejection of Lactation – Secretion and Ejection of MilkMilk

• Prolactin causes formation and secretion of milk in estrogen- and Prolactin causes formation and secretion of milk in estrogen- and progesterone-primed breastsprogesterone-primed breasts

• Oxytocin causes contraction of myoepithelial cells, leads to milk Oxytocin causes contraction of myoepithelial cells, leads to milk ejection through the nippleejection through the nipple

• Estrogens increase the number of oxytocin receptors on myoepithelial Estrogens increase the number of oxytocin receptors on myoepithelial cells cells

• Estrogens (and possibly also progesterone) antagonize the milk Estrogens (and possibly also progesterone) antagonize the milk production effect of prolactinproduction effect of prolactin

• After parturition, abrupt decline of estrogens and progesterone initiates After parturition, abrupt decline of estrogens and progesterone initiates lactation – in humans takes 1-3 days for the milk to “come in” lactation – in humans takes 1-3 days for the milk to “come in”

• Prolactin causes formation and secretion of milk in estrogen- and Prolactin causes formation and secretion of milk in estrogen- and progesterone-primed breastsprogesterone-primed breasts

• Oxytocin causes contraction of myoepithelial cells, leads to milk Oxytocin causes contraction of myoepithelial cells, leads to milk ejection through the nippleejection through the nipple

• Estrogens increase the number of oxytocin receptors on myoepithelial Estrogens increase the number of oxytocin receptors on myoepithelial cells cells

• Estrogens (and possibly also progesterone) antagonize the milk Estrogens (and possibly also progesterone) antagonize the milk production effect of prolactinproduction effect of prolactin

• After parturition, abrupt decline of estrogens and progesterone initiates After parturition, abrupt decline of estrogens and progesterone initiates lactation – in humans takes 1-3 days for the milk to “come in” lactation – in humans takes 1-3 days for the milk to “come in”

Prolactin – Synthesis and ControlProlactin – Synthesis and ControlProlactin – Synthesis and ControlProlactin – Synthesis and Control

• Produced by the lactotrophs cells of the anterior pituitary gland Produced by the lactotrophs cells of the anterior pituitary gland

• Under stimulatory control of thyroid releasing hormone (TRH)Under stimulatory control of thyroid releasing hormone (TRH)

• Increased release at night Increased release at night

• In females - increased release during pubertyIn females - increased release during puberty

• Prolactin levels are high during pregnancy - oestrogen causes an Prolactin levels are high during pregnancy - oestrogen causes an increase in numbers of lactotrophs increase in numbers of lactotrophs

• During lactation, suckling of the breast results in an increased release of During lactation, suckling of the breast results in an increased release of prolactin ( decreased PIH, increased PRH)prolactin ( decreased PIH, increased PRH)

• Response to suckling declines with time post-partum, may well remain Response to suckling declines with time post-partum, may well remain above normal for 18 months or more if suckling frequency is maintained above normal for 18 months or more if suckling frequency is maintained at a high level basal levelsat a high level basal levels

• Produced by the lactotrophs cells of the anterior pituitary gland Produced by the lactotrophs cells of the anterior pituitary gland

• Under stimulatory control of thyroid releasing hormone (TRH)Under stimulatory control of thyroid releasing hormone (TRH)

• Increased release at night Increased release at night

• In females - increased release during pubertyIn females - increased release during puberty

• Prolactin levels are high during pregnancy - oestrogen causes an Prolactin levels are high during pregnancy - oestrogen causes an increase in numbers of lactotrophs increase in numbers of lactotrophs

• During lactation, suckling of the breast results in an increased release of During lactation, suckling of the breast results in an increased release of prolactin ( decreased PIH, increased PRH)prolactin ( decreased PIH, increased PRH)

• Response to suckling declines with time post-partum, may well remain Response to suckling declines with time post-partum, may well remain above normal for 18 months or more if suckling frequency is maintained above normal for 18 months or more if suckling frequency is maintained at a high level basal levelsat a high level basal levels

Prolactin LevelsProlactin Levels

• High during pregnancy, drifts down to its normal level after the baby is High during pregnancy, drifts down to its normal level after the baby is bornborn

• By the end of the first week after birth, prolactin is down to 50 percent of By the end of the first week after birth, prolactin is down to 50 percent of its normal level, after three or four months, it is the same as it was before its normal level, after three or four months, it is the same as it was before pregnancypregnancy

• Every time the baby suckles, there is a new burst of prolactin telling the Every time the baby suckles, there is a new burst of prolactin telling the body to make milk and a burst of oxytocin telling it to eject the milkbody to make milk and a burst of oxytocin telling it to eject the milk

• The more the mother nurses the baby, the more milk the body will The more the mother nurses the baby, the more milk the body will produce; suckling is simply the message to the body to make more of it. produce; suckling is simply the message to the body to make more of it.

• High during pregnancy, drifts down to its normal level after the baby is High during pregnancy, drifts down to its normal level after the baby is bornborn

• By the end of the first week after birth, prolactin is down to 50 percent of By the end of the first week after birth, prolactin is down to 50 percent of its normal level, after three or four months, it is the same as it was before its normal level, after three or four months, it is the same as it was before pregnancypregnancy

• Every time the baby suckles, there is a new burst of prolactin telling the Every time the baby suckles, there is a new burst of prolactin telling the body to make milk and a burst of oxytocin telling it to eject the milkbody to make milk and a burst of oxytocin telling it to eject the milk

• The more the mother nurses the baby, the more milk the body will The more the mother nurses the baby, the more milk the body will produce; suckling is simply the message to the body to make more of it. produce; suckling is simply the message to the body to make more of it.

Contraceptive effect of high levels of Contraceptive effect of high levels of prolactinprolactin

In non breast-feeding womenIn non breast-feeding women

FSH levels quickly return to normal menstrual cycle FSH levels quickly return to normal menstrual cycle levels within a week or two post-partum; having the levels within a week or two post-partum; having the 11stst menstrual period menstrual period ++ 6 weeks after delivery 6 weeks after delivery

In non breast-feeding womenIn non breast-feeding women

FSH levels quickly return to normal menstrual cycle FSH levels quickly return to normal menstrual cycle levels within a week or two post-partum; having the levels within a week or two post-partum; having the 11stst menstrual period menstrual period ++ 6 weeks after delivery 6 weeks after delivery

Contraceptive effect of high levels of Contraceptive effect of high levels of prolactinprolactin

• In breast-feeding womenIn breast-feeding women

During lactational amenorrhoea (25-30 weeks) FSH levels During lactational amenorrhoea (25-30 weeks) FSH levels appear to be inadequate for ovarian functionappear to be inadequate for ovarian function

LH levels are very low immediately postpartum, by 15 to 20 LH levels are very low immediately postpartum, by 15 to 20 days increase significantly and remain throughout lactation days increase significantly and remain throughout lactation on the lower side of normalon the lower side of normal

Prolactin inhibits normal pulsatile secretion of GnRH, Prolactin inhibits normal pulsatile secretion of GnRH, inhibits GnRH action on pituitary, antagonize inhibits GnRH action on pituitary, antagonize gonadotropin action on ovaries, no midcycle LH surge gonadotropin action on ovaries, no midcycle LH surge anovulation anovulation

Prolactin inhibits the ovary Prolactin inhibits the ovary estrogen deficient estrogen deficient

• In breast-feeding womenIn breast-feeding women

During lactational amenorrhoea (25-30 weeks) FSH levels During lactational amenorrhoea (25-30 weeks) FSH levels appear to be inadequate for ovarian functionappear to be inadequate for ovarian function

LH levels are very low immediately postpartum, by 15 to 20 LH levels are very low immediately postpartum, by 15 to 20 days increase significantly and remain throughout lactation days increase significantly and remain throughout lactation on the lower side of normalon the lower side of normal

Prolactin inhibits normal pulsatile secretion of GnRH, Prolactin inhibits normal pulsatile secretion of GnRH, inhibits GnRH action on pituitary, antagonize inhibits GnRH action on pituitary, antagonize gonadotropin action on ovaries, no midcycle LH surge gonadotropin action on ovaries, no midcycle LH surge anovulation anovulation

Prolactin inhibits the ovary Prolactin inhibits the ovary estrogen deficient estrogen deficient

Newborn Baby Body-weight LossNewborn Baby Body-weight Loss

• Newborns are nourished from their mother's milk or from a Newborns are nourished from their mother's milk or from a bottle because they can only swallow liquids. bottle because they can only swallow liquids.

• Since newborns can only digest about 30 milliliters of mother's Since newborns can only digest about 30 milliliters of mother's milk or formula at a time, they must be fed often, usually about milk or formula at a time, they must be fed often, usually about every 4 hours. every 4 hours.

• They can lose as much as 10% of their body weights in the first They can lose as much as 10% of their body weights in the first few days after birth because they need more food than they can few days after birth because they need more food than they can consume. At about the tenth day of life, the newborn regains consume. At about the tenth day of life, the newborn regains the lost weight and starts to gain about 28 grams per day.the lost weight and starts to gain about 28 grams per day.

• Newborns are nourished from their mother's milk or from a Newborns are nourished from their mother's milk or from a bottle because they can only swallow liquids. bottle because they can only swallow liquids.

• Since newborns can only digest about 30 milliliters of mother's Since newborns can only digest about 30 milliliters of mother's milk or formula at a time, they must be fed often, usually about milk or formula at a time, they must be fed often, usually about every 4 hours. every 4 hours.

• They can lose as much as 10% of their body weights in the first They can lose as much as 10% of their body weights in the first few days after birth because they need more food than they can few days after birth because they need more food than they can consume. At about the tenth day of life, the newborn regains consume. At about the tenth day of life, the newborn regains the lost weight and starts to gain about 28 grams per day.the lost weight and starts to gain about 28 grams per day.

Thank youThank you