Medicine

PHYSIOLOGY OF PREGNANCY

PHYSIOLOGY OF PREGNANCY. PERINATAL CARE OF THE FETUS

 

Pregnancy (latin "graviditas") is the carrying of one or more offspring, known as a fetus or embryo, inside the uterus of a female.

l     The World Health Organization defines normal term for delivery as between 37 weeks and 42 weeks.

 

During pregnancy, the woman undergoes many physiological changes, which are entirely normal, including:

l     Cardiovascular

l     Hematologic

l     Metabolic

l     Renal

l     Respiratory, that become very important in the event of complications.

 

Body Water Metabolism

 

l     Condition of chronic water overload as a result of active Na and water retention

l      Body water increase 6.5Là 8.5L which provoke changes in osmoregulation  

 

Osmoregulation

l     Na retention increases, but serum Na decreases 3-4 mmol/l

l     Plasma osmolarity decreases 10 mOsm/kg

l     Enhanced tubular reabsorption of Na secondary to aldosterone,estrogen and deoxycorticosterone.

 

Cardiovascular Changes

HEART

l                             Displaced to the left and upward

l                             Apex is moved laterally

l                             Apparent cardiomegaly on chest x-ray

l                             Increase in left ventricular end- diastolic dimension

l                             Increase in left ventricular wall mass (mild hypertrophy)

l                             Grade II-III systolic flow murmurs at left lower sternal border

 

Respiratory Changes are progesterone induced:

 

l     Chronic hyperventilation

l     Minute volume increased

l     Tidal volume increased

l     Respiratory rate is unchanged

 

Upper respiratory tract

l     Hyperemia and edema induced by estrogen

l     Nasal stuffiness and epistaxis

l     Mechanical changes  (earlier than mechanical pressure of rising uterus

l     Chest circumference expands 5-7 cm

l     Subcostal angle increases from 68 to 103 degrees

l     Transverse diameter increases 2cm

l     Level of diaphragm rises 4cm but excursion is not impeded

l     Respiratory muscle function is not affected by pregnancy   

 

Hematologic Changes

l     40-50% increase in blood volume beginning at 6 weeks till 30 weeks

l     Both plasma volume and cell mass increase

l     Physiologic anemia of pregnancy nadiring at 30 weeks

l      Increase in erythropoietin and reticulocyte count

 

Iron Metabolism

l     Absorption in the duodenum in the divalent state

l     Trivalent food source must be converted by ferric reductase to divalent form

l     Feàenterocytesàbound transferrinàtransported to liver, spleen, muscle and bone marrowà incorporated into hemoglobin, myoglobin, ferritin or hemosiderin

l     1000mg iron requirement, about 3.5 mg/d of Fe

l     Requirements increase in third trimester

l     Fetus receives Fe through active transport

 

Fe supplementation

l     Fe supplemention usually not needed before 20 weeks

l     30mg of elemental FEà 325 mg ferrous gluconate

l                             Fe supplements  

l                             Ferrous sulfate ( 65mg elemental Fe)

l     Ferrous gluconate (35mg of elemental Fe)

 

Coagulation System

Hypercoaguable state as a result

of increased venous stasis and

vessel wall injury

 

Urinary System

l                             Renal hypertrophy

l                                                     Dilation of renal pelvis/calyces

l                                                     15mm on the right in 3rd trimester

l                                                     5mm on the left

l     Predisposition to pyelonephritis in the presence of assymptomatic bacteriuria

l                             Dilation of ureters to 2 cm

l                             Mechanical compression

l     Progesterone-induced smooth muscle relaxation

 

Stomach and Esophagus

 

l     Gastric production of hidrocloric acid is variable and sometimes exaggrated, especially during the first trimester. More commonly, gastric acidity is reduced.

l     Production of the hormone gastin increases significantly, resulting in increased sthomac volume and decreased stomach pH.

l     Gastric production of mucus may be increased.

l     Esophageal peristalses is deceased, accompanid by gastric reflux because of the slower emptying time and dilatation or relaxation of the cardiac sphincter.

l     Gastric reflux is more prevalent in later pregnancy owing to elevation of the stomach by the enlarged uterus.

 

Gastointestinal changes

Gastrointestinal motility may be reduced during pregnancy due to increased levels of progesterone, which in turn decrease the production of motilin, ahormonal peptide that is known to stimulate smooth muscle in the gut.Transit time of food throughout the gastrointestinal tract may be so much slower that more water than normal is reabsorbed, leading to constipation.

 

Metabolism

l     Weight gain is due not only to the uterus and its contents but also to increase breast tissue, blood and water volume in the form of extravascular and extracellular fluid. Deposition of fat and protein and increased cellular water are added to the maternal stores. The average weight gain during pregnancy is 12,5Kg.

l     During normal prgancy, approximately 1000g of weight gain is attributable to protein. Half of this is found in the fetus and the placenta, with the rest being distribute as uterine contractile protein, breast glandular tissue, plasma protein, and hemoglobin. Plasma albumin levels are decreased and fibrinogen levels increased.

 

Total body fat incresas during pregnancy, but the amount varies with total weight gain. During the second half of pregnancy, plasma lipids increase , but triglycerides, cholesterol and lipoproteins decreasesoon after delivery. The ratio of low density lipoproteins to high density lipoproteins increases during pregnancy

 

STAGES OF PRENATAL DEVELOPMENT

l     Three stages of prenatal development are distinguished.

l     Preembryonic stage lasts the first 2 weeks. Products of conception are called as conceptus.

l     The embryonic stage lasts from the start of the third week until the end of the eight week. From this period conceptus is called embryo.

l     Fetal period starts from the beginning of the ninth week through the full 41 weeks of development. Products of conception are called as fetus.

    Prenatal development ends with labour.

 

Preembryonic Stage includes:

l     fertilization

l     zygote formation

l     division of fertilized ovum

l     morula formatiom

l     formation of free blastocyst, as it travels through the woman’s fallopian tube towards the uterus

l     implantation of the ovum in the uterine wall

l     Primitive chorionic villi formation

l     Initial folding into layers – gastrulation beginning.

 

      Chorion and amnion begin to form during this period also.

 

Formation of free blastocyst

l     Blastomeres form the outer layer of single cells called the trophoblast (Greek for “nourishment of germ”).

      Certain trophoblast cells will develop into a membrane called the chorion, which eventually forms the fetal portion of the placenta, the organ that brings oxygen and nutrients to the fetus and remove wastes from it.

l     A clump of blastomeres inside the blastocyst forms the called as embryoblast.

     These cells will develop into the embryo, amnion plus its supportive extraembryonic membranes.

 

Implantation

l     Attachment of the blastocyst on the 7th day into uterine wall called implantation.

      It is possible thanks to digestive enzymes produced by the trophoblast.

l     The trophoblast (chorion) cells now secrete a hormone, human chorionic gonadotropin (hCG).

l     The cells continue to produce hCG for about 10 weeks. From the 7th day female urine contains hCG to respond positively to an at home pregnancy test.

 

 

GASTRULATION

l     The process of forming the primordial embryo is called gastrulation, and the layers are called germ layers.

l     The outer layer is called ectoderm, inner layer – is the endoderm, middle layer called the mesoderm forms. This three-layered structure is the primordial embryo or gastrula.

l     Ectoderm cells develop into the nervous system, sense organs, the outer skin layers, hair nails, and skin glands.

l     Mesoderm cells develop into bone, muscles, blood, reproductive organs and connective tissue.

l     Endoderm cells eventually form the organs and the linings of the digestive, respiratory, and urinary system. Gastrulation marks the start of morphogenesis.

 

 

EMBRYONIC STAGE

l     Development of the embryo.

l     Formation of supportive structures - include the placenta, umbilical cord, and certain extraembryonic membranes.

l     The placenta is completely developed at 10 – 14 weeks, establishing a vital link between mother and fetus that will last throughout pregnancy.

l     The yolk sac forms early and manufactures  blood cells until the liver takes over at 6 week.

l     The allantois forms the part of the yolk sac; it produces blood cells and eventually forms the umbilical arteries and veins.

l     The amniotic cavity expands with fluid as the yolk sac and allantois shrink.

l     The umbilical cord forms late in this period.

l     During the third week the primitive streak appears, and then, other rudiments of organs form, including the central nervous system, notochord, neural tube, heart, limbs, finger, toes, eyes, ears, and nose.

 

Critical periods of fetal development

l     Implantation

l     Morphogenesis and organogenesis

l     Placentation

 

Conceptus structure in the end of pregnancy

l     Fetus

l     Umbilical cord

l     Placenta

l     Amniotic Fluid

l     Amnion

l     Chorion

l     Decidua

 

Fetal characteristics

Classification

Gestational age (weeks of pregnancy

Weight, gram

Length, cm

Signs of maturity

“Deep pre-term fetus”

12 – 22

25 – 500

9 - 25

Absent

“Fetus pre-term”

22 –36+6days

500 – 2500

35 – 47

Absent

“Fetus in-term”

37 – 41

> 2500

(3200-3500)

> 47

(50-52)

Present

“Fetus post-term”

> 41

> 2500

> 48

Present

 

Signs of fetal maturity

l     Umbilical ring is between pubis and processes xyphoideus

l     Pink skin

l     Well-developed subcutaneous tissue,

l     Presence of lanugo in the shoulders and upper part of the back

l     Length of the hair on the head is above 2 cm

l     Nails are present till the top of the fingers

l     Well-developed ears and nose cartilage

l     Testes are present in the scrotum in the boys and labia major are covered labia minor in the girls

l     Active movements

l     Loud cry of the infant

 

Diameters of the fetal head at term

l     1. The suboccipitobregmatic (9.5 cm, 32cm), which follows from the middle of the large fontanel to the undersurface of the occipital bone.

l     2. The suboccipitofrontalis (10cm,33 cm) – from subocipital fossa to border of the hair.

l     3. The occipitofrontal (12 cm, 34 cm), which follows a line extending from a point just above the root of the nose to the most prominent portion of the occipital bone.

l     4.  The occipitomental (12.5-13 cm, 39-41cm), from the chin to the most prominent portion of the occiput.

l     5.The sublingquobregmatica (9,5 cm, 32 cm).

l     6.  The biparietal (9.5 cm), the greatest transverse diameter of the head, which extends from one parietal boss to the other.

l     7.  The bitemporal (8.0 cm), the greatest distance between the two temporal sutures.

Diameters of the fetal body at term

 

l     Biacromial distance – 12cm, 34-35 cm

l     Bisiliacus distance – 9cm, 27-28 cm

 

Decidua (maternal membrane) - under the influence of progesterone, decidual changes occur in the endometrium of the pregnant uterus.

l     The decidua basalis – is the decidual layer directly beneath the site of implantation.

l     The decidua capsularis  - is the layer overlying the developing ovum and separating it from the rest of the uterine cavity.

l     The decidua vera (parietalis) is the remaining lining of the uterine cavity. The space between the decidua capsularis and decidua vera is obliterated by the fourth month with their fusion.

        The decidua parietalis and the decidua basalis are composed of three layers each: Zona compacta, Zona spongiosa, Zona basalis.

       The compacta and the spongiosa together form the zona functionalis (functional zone).

        The basal zone remains after delivery and gives rise to new endometrium.

 

Amnionic Fluid

Their production begins from the 12 days of gestation. The normal volume of amniotic fluid at the end of pregnancy is 1-1,5 L.

       Functions:

l     Physical protection.

l     Allows the fetus for growth, movement, and development.

l     Epidermal growth factor (EGF) and EGF-like growth factors, such as transforming growth factor-a, are present in amnionic fluid. Thus, ingestion of amnionic fluid into the lung and gastrointestinal tract may promote growth and differentiation of these tissues by “inspiration” and swallowing amnionic fluid.

l     Peptides, such as endothelin-1 also are present in amnionic fluid, and they may be involved in fetal developmemt and surfactant synthesis that becomes increasingly important for fetal pulmonary development.

l     Interleukin, prostaglandines and cytikines synthesis as a result of infection entering.

l     Antibacterial activity and acts to inhibit the growth of potentially pathogenic bacteria.

l     During labour and delivery, the amniotic fluid continues to serve as a protective medium for the fetus, aiding dilatation of the cervix thanks to forebag formation.

 

Placental villi

l     Villi can first be distinguished easily in the human placenta on about the 12th day after fertilization.

l     By about the 17th day, fetal blood vessels are functional and a placental circulation is established.

l     Maternal blood enters the intervillous space from the spiral arteries in fountain-like bursts;  thus, maternal blood (which is propelled totally outside of the maternal vessels) sweeps over and directly bathes the syncytiotrophoblast.

l     The maternal surface of the syncytiotrophoblast consists of a complex microvillous structure; there is continual shedding and reformation of these microvilli during the course of pregnancy.

l     At term, the placenta contains approximately 12 m2 of villous surface area for maternofetal exchange.

 

Placenta at section

l     Normally placenta located in the are of uterine fundus.

l     Placenta consists of fetal and maternal parts.

l     There is a variable number (10 to 38) of slightly elevated convex areas called lobes (or if small, lobules) on the maternal surface. These lobes are separated, albeit incompletely, by grooves of variable depth, the placental septa. The lobes are often called cotyledons.

 

Type of human placentation

The term hemochorioendothelial is derived as follows:

l     hemo refers to maternal blood, which directly bathes the syncytiotrophoblast;

l     chorio is for chorion-placenta, which in turn is separated from fetal blood by the wall of the fetal capillaries (endothelial) that traverse the intravillous space.

l      As the lacunae join, a complicated labyrinth is formed that is partitioned by solid cytotrophoblastic columns. The trophoblast-lined labyrinthine channels and the solid cellular columns form the intervillous space and primary villous stalks, respectively.

 

Principle of feto-maternal circulation

Substances that pass from maternal blood to fetal blood must traverse:

l     (1) syncytiotrophoblast,

l     (2) stroma of the intravillous space,

l     (3) fetal capillary wall.

   Although this histological “barrier” separates the blood in the maternal and fetal circulations, it does not behave in a uniform manner like a simple physical barrier.

 

Placental functions

l     Endocrine

l     Transfer of nutrients

l     Excretory - removal

   of the products of fetal catabolism

l     Barrier

l     Oxygen-transport

 

The anatomical parts of the endocrine system of the placental arm of the fetal–maternal communication system

ACTH from the fetal pituitary gland stimulates fetal adrenal steroidogenesis. Fetal adrenal dehydroepiandrosterone sulfate and 16a-hydroxy-dehydroepiandrosterone sulfate are transported to the placenta and converted to estradiol-17b and estriol, respectively.

           Fetal liver is the major site of production of low-density lipoprotein (LDL) cholesterol, the principal precursor for fetal adrenal steroidogenesis.    

           Cholesterol, derived from LDL in maternal plasma, serves as the precursor for progesterone biosysnthesis in placenta.

 

Placental hormones

1.  Protein hormones of the placenta:

chorionic gonadotropin (cHG)– it is maintain the function of the corpus luteum during early gestation, promote uterine vascular vasodilation and myometrial smooth muscle relaxation, relaxin secretion by the corpus luteum, stimulate thyroid activity, and some more basic forms also stimulate iodine uptake

human lactogen – its actions include lipolisis and an increase in the levels of circulating free fatty acids, thus providing a source  of energy for maternal metabolism and fetal nutrition; and inhibition of both the uptake of glucose and of gluconeogenesis in the mother, thus sparing both glucose and protein (anti-insulin action).

2. Steroid hormones of the placenta:

estrogens;

progesterone.

3. Chorionic adrenocorticotropin and thyrotropin, growth hormone variant, parathyroid hormone-related protein (PTH-rP), calcitonin, and relaxin  – no significant role has been established for this substance in normal human pregnancy.

4. Hypothalamic-like-releasing hormones of the placenta – the role of these hormones cannot be resolve.

5. Inhibin – is produced in cytotrophoblasts and may act to regulate hCG release or secration in the placenta

 

Umbilical Cord

l     Its diameter is 0.8 to 2.0 cm, with an average length of 55 cm and a usual range of 30 to 100 cm. Generally, cord length less than 32 cm is considered abnormally short.

l     Folding and tortuosity of the vessels, which are longer than the cord itself, frequently create false knots.

l     Runs from the fetal umbilicus to the  point of its insertion in the placenta.

l     The single umbilical vein in the cord carries oxygenated and nutrient –containing blood from the placenta to the fetus.

l     Blood is returned to the placenta through the two umbilical arteries.

l     A small amount of connective tissue, within which is  distributed a gelatinous material known as Wharton jelly, supports these structures.

l     The umbilical cord is devoid of nerves and lymphatic.