Physiology notes about pregnancy and related topics

Physiology

1. Pregnancy
Dr. Sreelekshmy T A
Assistant professor
Department of Physiology

2. Specific learning objectives
•Introduction
•Fertilization and implantation
•Placenta-functions
•Maternal changes during pregnancy
•Pregnancy tests
•Parturition/Labour
•Puerperium
•Fetal circulation

3. Introduction
•Pregnancy occurs when a matured ovum is
fertilized by a sperm.

4. Physiology of pregnancy
1. Transport of gametes-
a.)Transport of ovum

b.)Transport of sperms in the female genital
tract

5. Transport of ovum

Ovum expelled into peritoneum

Fimbria of fallopian tube pickup ovum

Movement of cilia & contractions of smooth muscle
fibers in wall of fallopian tube carries ovum to
ampulla

7. Transport of Sperm
•Many Sperms die in the vagina due its acidic
environment (vaginal pH is 5.5–6).
•Transport of Sperm in the Cervix
•Passage of sperms through cervix is favored
by: Nature of cervical mucous&orientation of
mucous
•Transport of sperm in the uterus due to
sperm’s own motility and uterine
contractions.

8. Transport of Sperms
Motility of sperms depends upon
•PH of the fluid medium-neutral/alkaline PH enhance
motility-alkaline semen neutralizes vaginal acidic fluid.
•Cervical mucus secretions-thin watery during
ovulation.
•Fluid currents- in vagina ,uterus towards exterior Resist
motility
•Temperature-high temp.---short life span(life span in
female genital tract -24-48 hrs at body temperature)
•Hormones-
oxytocin,estrogens,prostaglandins,progesterone-all
favours

9. •Though several millions of sperms are
deposited in the vagina, only few reach the
fallopian tube.
•This is the major reasons that there must be
many millions of motile sperms in the
seminal fluid for fertilization to occur.
•Thus, decreased count and motility of sperms
lead to infertility in males.

10. Capacitation write briefly
•Immediately after ejaculation in female genital
tract , the sperm undergo certain changes
which enable it to fertilize an ovum

11. Capacitation
Ejaculated sperm can fertilize ovum only after
capacitation.

•Cholesterol contents of acrosomal membrane
decreases --become weak---release of enzymes

•Membrane of sperm become–permeable to
calcium ions
-Tail shows increased activity- whiplash movment
-Trigger release of enzymes from acrosome

12. Fertilization-write briefly

•Fertilization is the process of union of sperm
with egg that results in zygote formation.

13. Fertilization

Fertilization takes place in following steps:
1.Fusion of sperm with egg,
2.Acrosome reaction & Sperm penetration
3.Polyspermy block
4.Formation of zygote.

14. 1.Fusion of sperm with egg
•The zona pellucida contains glycoproteins that
serve as receptors for sperm surface proteins.

15. 2. Acrosome Reaction-write briefly
•The binding sperm to the zona pellucida
triggers acrosome reaction in the bound
sperm, which is required for sperm
penetration

16. 2.Acrosome Reaction
i.Change in membrane of sperm head
ii.Increased fluidity of the membrane of the sperm
head.
iii.Increased calcium permeability of the sperm
membrane
iv.Digestion of a part of zona pellucida: role of acrosin
v.Penetration of sperm through perivitalline space
vi.Fusion of sperm head with egg membrane-fertilin.

17. •Acrosin-trypsin like protease –proteolytic
enzyme that digest zona pellucida at the site
of binding
•As zona pellucida gives way –sperm reaches
perivitalline space –space surrounding egg
membrane-reach egg plasma membrane
•Fertilin –Sperm surface protein

18. Sequential events in fertilization

19. 3.Polyspermy Block
•Only one sperm penetrates egg , as soon as
one sperm penetrates ,a series of changes
occur in the egg ,that prevent entry of
additional sperms called polyspermy block.

20. 3.Polyspermy Block
•Two mechanisms of polyspermy block

1.Changes the membrane potential of the egg

2. Inactivation of sperm binding sites on zona
pellucida & Hardening of the entire zona
pellucida

21. •Secretory vesicles located in the periphery of
egg cytoplasm release their contents into
perivitalline space –vesicles contain enzymes
they cause
•Inactivation of sperm binding sites on zona
pellucida
•Hardening of entire zona pellucida

22. 4.Zygote Formation
•Fertilized egg is called zygote
•Fertilized egg completes its second meiotic
division in next few hours.
•As a result of second meiotic division –second
polar body formed &extruded
•Remaining haploid nucleus (23 chromosomes)
transformed to female pronucleus
•On entering egg , sperm head swells ---male
pronucleus formed

23. 4. Zygote Formation
•Both male & female pronuclei migrate to the
center
•DNA of chromosomes replicate and pronuclei
fuses
•Pronuclear membrane break down , cell
;ready to under go mitotic division
•Completes the process of fertilization &
fertilized egg called zygote

25. IMPLANTATION
•Implantation of a fertilized ovum involves
following steps
1.Formation of blastocyst.
2.Transportation of blastocyst in uterine cavity
3.Implantation of blastocyst in the
endometrium
4.Decidual reaction

26. 1. Formation of blastocyst
•Morula (16-cell stage)
•Blastocyst (100-cell stage).
•Trophoblast
•Inner layer (cytotrophoblast)
•Outer layer (syncytiotrophoblast).

29. 2. Transportation of blastocyst in
uterine cavity.
•Assisted by
Ciliary movements
Fluid currents

30. 3. Implantation of blastocyst in the
endometrium.

•Syncytiotrophoblast-release proteolytic
enzymes –digest liquefy the endometrial cells
•The blastocyst then erodes and burrows into
the endometrium
•On dorsal wall of uterus -

33. 4. Decidual reaction
•After implantation-endometrium is called
decidua
•The stroma cells of the endometrium get
enlarged-decidual cells
•Change in stromal cells are called decidual
reaction
• Vacuolated, filled with glycogen and lipids.-
nutrition for embryo

34. Placenta

35. PLACENTA

•Placenta is a temporary organ formed during
pregnancy.
•It is an important link between the mother
and the fetus.
•Disc shaped
•Diameter 15-20cm
•Weight -500gm

36. •Chorionic villi, the functional units of placenta
begins to form at about 12th day from
fertilization

38. •Chorionic villi (fingerlike projections) originate
from trophoblast cells and extend from the
chorion into the endometrium.
•The chorionic villi contain a rich network of
capillaries. Each villus is surrounded by a pool
of maternal blood called placental sinus,
supplied by maternal arterioles.

39. The placental membrane
•The maternal and the fetal blood do not mix
with each other.
•They are separated by a placental membrane,
made up of the layers of the wall of the villus.
From the fetal side
•These are

40. The placental membrane

41. The placental membrane-layers
•Endothelium of fetal blood vessels and its
basement membrane,
• Surrounding mesenchymal tissue (connective
tissue)
• Cytotrophoblast and its basement membrane
•Syncytiotrophoblast

42. Functions of placenta-short essay
•Endocrine function
•Respiratory function
•Nutritive & storage function
•Excretory function
•Immunological function

43. Endocrine Function
The syncytiotrophoblast of the placenta serves
as an endocrine gland.
•Human chorionic gonadotropins (HCG)
• Human chorionic somatomammotropins
(HCS)/HPL
• Human chorionic thyrotropin(hCT)
• Placental progesterone
• Placental oestrogens

44. Human chorionic gonadotropins(HCG)

•Structure-(glycoprotein hormone two
subunits: α and β) Alpha chain similar to
alpha subunit of LH,FSH,TSH
•Binds with LH receptors in the corpus luteum
•Secretion-appears in maternal plasma as early
as 6
th
day after fertilization.( detected by RIA)
Its concentration increases rapidly to reach a
peak in about 10–12 weeks of gestation.

45. Physiological effects of HCG

•Maintenance of corpus luteum of pregnancy
•Stimulates progesterone secretion from corpus
luteum
•Helps in sexual differentiation in male fetus.
•Stimulates maternal thyroid gland function
•Immunosupressive action –maintenance of
pregnancy
•Placental steroidogenesis

46. •Corpus luteum doubles due to the action of
hCG
•Helps in sexual differentiation in male fetus
In male fetus hCG stimulate leydig cells to of
testis to secrete testosterone –male genitalia
is formed & help in descend of testis

47. •HCG is a luteotropic hormone.-
•Its actions are similar to luteinizing hormone
(LH) of anterior pituitary hence also called
second luteotropic hormone.
• It maintains the functions of the corpus
luteum up to 7 weeks after conception until
fetoplacental unit is able to synthesize its own
oestrogen and progesterone.

48. •Clinical importance (application) of HCG is the
presence of HCG in the urine, which forms the
basis of all the pregnancy tests.
• Human chorionic gonadotropin appears in
the urine as early as 14 days after conception

49. Human chorionic somatomammotropin
/Human placental lactogen-
Other names-chorionic growth hormone prolactin
(CGP) or placental growth hormone
•Produced from syncytiotrophoblast
•It promotes growth of mammary gland and
stimulates production of milk.
•It stimulates somatic growth of the fetus
•Decreases insulin sensitivity-increased glucose
availability of fetus.
•It causes maternal lipolysis and releases FFA from
fat tissues.

50. Human chorionic thyrotropin

•Secreted by the placenta has properties quite
similar to that of thyroid stimulating
hormones.
•The physiological role of this substance is not
very clear.

51. Estrogen & Progesterone
•As far as steroid hormone synthesis is
concerned ,placenta is an incomplete organ
•It depends on the precursors mainly from fetal
and maternal sources
•Concept of ‘Fetoplacental unit’

52. Fetoplacental unit- write briefly

53. Fetoplacental unit
•By 12
th
week of development fetus &placenta
function as a single unit –fetoplacental unit
•Important role in steroidogenesis(estrogen
&Progesterone)
•From mother cholesterol enters placenta –
pregnenolone &progesterone formed.
•Part of progesterone reaches the fetal adrenals &
converted into cortisol,corticosterone-rest
escapes to maternal circulation.

54. Fetoplacental unit
•Pregnenolone reaches fetal adrenal &liver
converted to DHEAS,16- OH-DHEAS
•16 –OH-DHEAS is the main source of estriol
(important estrogen during pregnancy.)
Clinical aspect-Urinary estimation of estriol (16
OH DHEAS-principal substrate for estriol )in
mother is used as an index to monitor the
health of fetus.

55. Physiological effects of placental
progesterone
•It helps to preserve the pregnancy by promoting the
growth of endometrium.
•Progesterone has a marked inhibitory effect on the
contractions of uterus.
•It causes development of alveolar system of mother’s
breast
•Progesterone has an immunosuppressive role in
protecting the fetus.
•By acting as a precursor for the corticosteroid synthesis
by the fetal adrenal cortex, it helps in growth and
development of the fetus.

56. Placental estrogens
•It causes growth and development of
maternal reproductive organs
•Estrogen stimulates development of
lactiferous ductal system in mammary glands
•It stimulates hepatic synthesis of thyroxine
binding globulins, steroid-binding globulins
and angiotensinogens.
•It also stimulates renin secretion

57. •Relaxation of pelvic ligaments pubic
symphysis in conjunction with relaxin.
•Just before term ,estrogen to progesterone
ratio increases and uterus is dominated by
oestrogen
•Increases uterine contractility& the
sensitivity of uterus to oxytocin

58. Other placental hormones
A number of other substances which are secreted from
placenta are:
• Corticotropin-releasing hormone (CRH)
• β-endorphins
• α MSH
• Dynorphin A
• Gonadotropin-releasing hormones (GnRH)
• Inhibin
• Leptin
• Prolactin
• Prorenin

59. Respiratory function


•Diffusion of carbon dioxide
•Diffusion of oxygen

60. Respiratory function
•Diffusion of carbon dioxide
•Pco2 of fetal blood is 2-3mmHg higher than
maternal blood-even though gradient is low
CO2 diffuses with ease because
1.Diffusion capacity of Co2 is 20 times more
than O2 through placental membrane

61. •Diffusion of oxygen
Mean Po2 in mother-50mmHg
Po2 in fetal blood in placenta-30mm Hg
Increased oxygen extraction from maternal blood
due to
1.High affinity of HbF for O2
2.Hemoglobin content more in fetus than in
mother
3.Double Bohr effect

62. Bohr effect
•Decreased in O2 affinity of Hb when PH of
blood falls due to increase in PCO2 –Bohr
effect

•Bohr effect on the maternal side

•Opposite of Bohr effect on fetal side

63. Double Bohr effect
Bohr effect on the maternal side & opposite of Bohr
effect on fetal side --- increased extraction of
oxygen from maternal blood.
•PCo2 of maternal blood increases – PH decreases
–ODC shifted to right-increased unloading of O2

•While flowing through placenta ,Pco2 of fetal
blood decreases –PH increases-shift ODC to left-
increased loading of O2

65. Nutritive & storage function

•Substances molecular weight less than 1000
easily pass through placental membrane--
Glucose, amino acids , ascorbic acids, fatty
acids, ketoacids
•Storage of glucose , Na , Ca , iron

66. Excretory function

•Urea

•Uric acid

•Creatinine

67. Immunological function
•Placenta –protect fetus from incompatibility
produced between mother &fetus
•Restrict entry of antigens & toxic materials
from maternal to fetal blood
•Placenta prevents immunological maternal
attacks by destroying T lymphocytes-prevent
rejection of fetal tissue
•Passive immunity

68. PREGNANCY TESTS
•Based on presence of HCG in urine
•Concentration to obtain a positive test-2500
IU/L
•Detected in urine on 14
th
day of conception
Types
•Biological tests-
•Immunological tests-

69. PREGNANCY TESTS
•Biological tests-outdated
Based on the luteinizing activity of HCG
Urine of pregnant women injected into a virgin
animal –ovulation occurs –detected by
hemorrhagic spots-

71. Biological tests-

72. Immunological tests-write briefly

1.Gravindex Test
•Immunological pregnancy tests are based on
the antigenic properties of HCG.
•Requirements
Suspected urine sample of the lady-
Antiserum containing antibodies against HCG-
Latex particles coated with HCG

73. •This test is done in control and test samples of
urine.
•Gravindex antigen-latex particles coated with
HCG
•Gravindex antibodies-Antibodies against HCG is
prepared by injecting urine of pregnant women
containing HCG into rabbits—after 2 weeks blood
from the rabbit is withdrawn ---serum seperated -
---Anti HCG antibodies are prepared

74. Control
Urine without HCG + HCG antiserum
↓
No neutralization
↓
Add HCG coated latex particles-
Gravindex antigen
↓
Visible agglutination
↓
No pregnancy

75. Test
•Urine containing HCG + HCG antiserum
↓
Neutralization of antibody
↓
Add HCG coated latex particle
↓
No visible agglutination
↓
Pregnancy

76. False positive results
•Tumors
Vesicular mole
Choriocarcinoma
Chorioepithelioma
•Proteinuria
Later months of pregnancy- Test become
negative

77. 2)RIA (Radioimmunoassay )
Most sensitive for quantification of antigens or
antibodies.
•Based on competition for a fixed amounts of
specific antibody between a known
radiolabelled antigen & unknown unlabelled
(test) antigen( HCG containing urine or serum)
•Radio active-Iodine 125 is used

79. •Labelled and unlabelled antigen competes for
the limited binding sites on the antibody
•After antigen-antibody reactions ,antigen is
separated into free and bound fractions
&their radioactivity is measured.
•Radio activity of bound form is measured and
from standard curve ,HCG value is determined

81. •Reference curve has to be prepared for
calculation

82. 3.ELISA-Enzyme linked immunosorbent Assay
Requires only very small quantities of test
reagents
•Principal same as that of RIA,except that
enzyme is used instead of a radioactive
substance
•Enzyme act as substrate to produce a color in
a positive test.

84. •Appearance of a red color in test band is
positive for pregnancy diagnosis and a
colorless response as negative result.

85. Other tests
USG:
•Detect pregnancy by 29-35 days of gestation
•Gestational sac by 5weeks
•Foetal pole & cardiac activity by 6 weeks

86. PHYSIOLOGICAL CHANGES IN
MOTHER DURING
PREGNANCY

•Structural changes

•Systemic changes

87. PHYSIOLOGICAL CHANGES IN MOTHER
DURING
PREGNANCY-indu

The normal average duration of pregnancy in
human beings is 280 days (40 weeks) and is
calculated from the first day of the last
menstrual period.

88. Structural changes
Uterus.
•Increase in the size of uterus.

•The enlargement is mainly due to hypertrophy
and to some extent hyperplasia of the
myometrial smooth muscle fibers

89. Structural changes
Ovaries.
•The follicular changes and ovulation do not
occur because FSH and LH of anterior pituitary
are inhibited

90. Structural changes
Cervix.
• Endocervix gets hypertrophied
•Cervical glands increase in number and their
secretions form a plug that closes the cervical
canal .
• Tough cervix becomes soft.

91. Structural changes
Mammary gland
• Size increased due to:
Development of new ducts & alveoli; fat
deposition

• Pigmentation of nipple & areola

92. Systemic changes
HEMATOLOGIC CHANGES -
• Blood volume increases 30% (plasma vol.
more than Red cell volume)-hemodilution
Physiological anaemia of pregnancy
• Moderate leucocytosis, platelet count slight
decrease.
↑in procoagulant activity

93. •HEMATOLOGIC CHANGES – contd.
•Increase in : fibrinogen, factors VII, VIII, IX and
X.
•The hypercoagulability of the blood plays an
significant role of hemostasis at the time of
separation of placenta during delivery.

94. CARDIOVASCULAR SYSTEM CHANGES
•Heart displaced laterally & upwards;
•Cardiac output increases-5-7 L/min

• SBP-N/ ↓
• DBP decreased by 20wks & then inc. to normal

•Regional blood flow increases
•Increased venous pressure

95. CARDIOVASCULAR SYSTEM CHANGES
Increase in cardiac output – due to increases in heart
rate & stroke volume (due to increase in blood volume)

Fall in DBP- due to effect of vasoactive substances-
kinins,Endothelium derived releasing factor,NO

Increase in venous pressure-gravid uterus press on
pelvic veins –increase in venous pressure-increase in
femoral venous pressure –predisposes to piles,varicose
veins,peripheral venous thrombosis

96. Respiratory system-
•Anatomical changes- ↑in Transverse diameter,
↑ subcostal angle both ↑airflow
•Tidal volume↑, pulmonary ventln.↑(High
levels of plasma progesterone during
pregnancy increase the sensitivity of
respiratory neurons to CO2 resulting in
hyperventilation), oxygen consumption
increases

97. •Gas exchange across the alveoli is greatly
enhanced due to a marked increase in the
pulmonary blood flow
Oxygen consumption.
• Oxygen consumption of body increases by
15% to meet the demands of growing fetus
and for the extra work of heart, uterus and
other tissue.

98. RENAL SYSTEM-
•Renal blood flow & GFR increased;
•Glycosuria
•Inc. freq of micturition,
•Proteinuria,
•Excess of water retention(due to decreased
protein concentration and retention of sodium.)

99. •GASTROINTESTINAL SYSTEM CHANGES
Hypochlorhydria,
GIT motility decreases
Morning sickness

100. ENDOCRINE SYSTEM CHANGES
•Ant pituitary- Prolactin, ACTH,TSH --increased;
GH,LH & FSH--- decreased
•Thyroid gland- enlargement; incr. TBG
•Adrenal cortex- GC & MC increased
•Parathyroid – incr. PTH---- help in calcium
absorption from gut decreases excretion –full
fill the increased calcium requirement of
pregnancy

101. Nervous system-
•Psychological changes-craving for particular
food items;
• Alt. in behaviour, emotions
•Mood changes
•Psychosis

102. METABOLIC CHANGES
•The basal metabolic rate-increases
•Protein metabolism-nitrogen retention and positive
nitrogen balance
•Carbohydrate metabolism-Blood glucose level
increases, Ketosis
•Fat metabolism -There occurs an increase in plasma
concentration of cholesterol, phospholipids and
triglycerides.

103. •Mineral metabolism-
•Calcium and phosphorus-mother retains about 50 g
of extra calcium and 30–40 g of phosphorus
•Iron metabolism - Iron requirement increases during
pregnancy and lactation.

104. CHANGES IN THE SKIN
•Hyperpigmentation-chloasma, linea alba(increase
ACTH &alpha-MSH)

105. PARTURITION

106. PARTURITION
•Parturition is the process by which baby is
born.

107. PARTURITION-Stages
3 stages of labour:
•1
st
stage : beginning of painful contractions to
the full dilatation of cervix

•2
nd
stage : full dilatation of cervix to expulsion
of fetus

•3
rd
stage : expulsion of fetus to expulsion of
placenta and membranes

108. CONTROL OF PARTURITION
•Hormonal factors
•Mechanical factors

109. CONTROL OF PARTURITION
HORMONAL FACTORS
•Activation of fetal hypothalamic-pituitary-
adrenal axis.
•Role of altered estrogen–progesterone ratio.
•Role of oxytocin and prostaglandins.