Session 8: Pregnancy Flashcards
Describe Implantation (quick recap)
By the time the blastocyst enters the uterine cavity (4-5 days after fertilisation), the endometrium (simple columnar) is ready to receive it for pregnancy to be established. After a day or so in the uterine cavity, the blastocyst implants into the endometrium.
[*] The syncytiotrophoblast is good at transport
[*] The cytotrophoblast is the stem cell layer – increases size of syncytiotrophoblast and carries out repair.
- Implantation involves interaction between trophoblast cells and the epithelium of the uterus.
- Further embedding of the blastocyst into the endometrium is dependent upon the invasive property of the trophoblasts, which by now has an outer layer called the Syncytiotrophoblast differentiated from the underlying Cytotrophoblast.
What has happened by the 10th day after fertilisation? Describe the early placenta
By the 10th day after fertilisation, the blastocyst is fully embedded within the endometrium.
[*] The uterine gland secretes a large number of secretions/
[*] Implantation is interstitial: uterine epithelium is breached and conceptus implants within stroma.
[*] Placental membrane becomes progressively thinner as the needs of the foetus increase.
[*] Placenta is haemochorial: one layer of trophoblast ultimately separates maternal blood from fetal capillary wall (optimizing transport)
What has happened by the end of Week 2? What happens next?
Initially the chorionic sac and the amniotic sac are separate but as the embryo enlarges and the volume of amniotic fluid increases, this leads to the amniotic sac making more contact with the chorionic sac. The villi recede – become restricted to a zone and become specialised for function
What are the aims of implantation?
[*] Establish the basic unit of exchange
- Primary villi: early, finger-like simple projections of trophoblast
- Secondary villi: invasion of mesenchyme into core (as differentiation occurs)
- Tertiary villi: invasion of mesenchyme core by fetal vessels
[*] Anchor the placenta
- Establishment of outermost cytotrophoblast shell (foetal and maternal tissues are enclosed)
[*] Establish maternal blood flow within the placenta (around chorionic villi to optimise transport)
Describe the histology of implantation
[*] The endometrium is prepared for implantation
Decidualisation
- Pre-Decidual cells
- The decidual reaction provides the balancing force for the invasive force of the trophoblast.
- Stimulated by progesterone
- Without this balancing force, complications such as haemorrhage can occur e.g. in ectopic pregnancy and conditions characterised by excessive invasion (starting to invade myometrium)
- Remodelling of Spiral Arteries (elaboration of spiral arterial blood supply)
- Creation of low resistance vascular bed
- Maintains the high flow required to meet fetal demand, particularly late in gestation
Describe what happens when implantation goes wrong - including ectopic pregnancy, placenta praevia, and incomplete invasion of trophoblast
[*] Ectopic pregnancy
- Implantation at site other than uterine body
- Most commonly fallopian tube
- Can be peritoneal or ovarian
- Can very quickly become a life-threatening emergency
[*] Placenta Praevia
- Implantation in the lower uterine segment
- Can cause haemorrhage in pregnancy
- Requires C-section delivery
[*] Incomplete Invasion of trophoblast
- Placental insufficiency
- Pre-Eclampsia
How may twinning occur at different stages?
Twinning: the degree to which membranes are shared in monozygotic twins can vary
[*] Two morulas and blastocysts => separate implantation sites => 2 amnions and two chorions
[*] One morula => 2 ICMs and bilaminar discs => 2 amnions but a shared chorion
[*] One blastocyst and bilaminar disc => amnion and chorion are both shared => 2 primitive streaks
Describe the development of the placenta
- A good placenta determines a good pregnancy. It represents the interface between the mother and developing child, the structure through which nutrients are supplied from the mother and waste is removed from the embryo/foetus.
- It has a developmental programme in its own right and its structure changes over time in ways that reflect the changes in function required of it.
- Development of the placenta begins soon after fertilisation at compaction, with cells of the outer cell mass destined to develop into the structures that support the embryo/fetus during the pregnancy.
[*] The embryo/fetus is enclosed by the amnion and chorion membranes in a protective sac, and the placenta develops as a specialisation of outer membrane, the chorion.
[*] This specialisation begins as implantation gets underway and takes the form of finger-like projections, called chorionic villi.
[*] These villi are the functional units of the placenta and represent the point of exchange between the maternal and foetal circulations.
[*] In essence, the chorionic villi consist of a vascularised core covered by 2 epithelial layers.
As the placenta matures to meet the increasing demands of the growing fetus, it adapts by decreasing the interhaemal distance. This is achieved by thinning of the trophoblast layer(s), margination of the fetal capillaries of the core of the villi and increasing the surface area for exchange through increased branching of the villus tree.
What happens when development of the placenta goes wrong?
[*] These processes become exaggerated in situations where the demand for transported materials or restriction on the maternal side leads to a deficit.
[*] For example, placentae from pregnancies in women who smoke or live at high altitude have reduced interhaemal distances when compared to “normal”.
[*] Of course, this compensation has a limit and there are circumstances when the placenta’s powers of compensation are exceeded.
[*] Placental defects are among the major risk factors for intrauterine growth restriction, and impaired fetal growth has been linked to long-term adult health problems (Barker hypothesis – the fetal origins of adult disease)
Describe the components of the placenta by the beginning of the 4th month
- A foetal position
- Formed by the chorion frondsum
- Bordered by the chorionic plate
- A maternal portion
- Formed by the decidua basalis
- The decidual plate is most intimately incorporated into the placenta
[*] Between the chorionic and decidual plates are the Intervillous Spaces, which are filled with maternal blood.
What happens to the placenta during the fourth and fifth months?
- During the fourth and fifth months, the decidua forms a number of Decidual Septa, which project into the intervillous spaces but do not reach the chorionic plate. These septa divide the placenta into a number of compartments or Cotyledons.
- As a result of the continuous growth of the fetus and expansion of the uterus, the placenta also enlarges. Throughout pregnancy it covers approximately 15-30% of the internal surface of the uterus.
Describe the placental barrier during first trimester, at term and at parturition
First Trimester Placenta
[*] Placenta established
[*] Placental ‘barrier’ (‘leaky sieve’) to diffusion still relatively thick.
[*] Complete cytotrophoblast layer beneath syncytiotrophoblast
Term Placenta
[*] Surface area for exchange dramatically increased
[*] Placental ‘barrier’ is now thin (transport is now very efficient)
[*] Cytotrophoblast layer beneath syncytiotrophoblast lost (as its only job was to repair syncytiotrophoblast – now no longer continuous)
The placenta is shed at parturition and the massive blood supply to the implantation site is shut down. If the placenta fragments during labour, this can result in retained placenta which impairs shut-down of the utero-placental circulation, and consequently can cause serious post-partum haemorrhage.
Describe the arrangement of fetal blood vessels within the placenta
The umbilical arteries and veins project into tertiary villi, which are bathed in oxygenated maternal blood.
- Two Umbilical Arteries: carries deoxygenated blood from fetus => placenta
- One Umbilical Vein: carries oxygenated blood from placenta => fetus
Cotyledons receive their blood through 80-100 spiral arteries that pierce the decidual plate.
[*] Pressure in these arteries forces oxygenated blood deep into the intervillous spaces and bathes the numerous small villi of the villous tree in oxygenated blood.
[*] As the pressure decreases, blood flows back from chorionic plate towards the decidua, where it enters the endometrial veins.
Describe the factors influencing the passive diffusion of substances across the placenta
Materno-fetal exchange occurs through a variety of means, and involves both simple and facilitated diffusion, active transport and receptor-mediated endocytosis. The combined utero-placental and fetal-placental circulations represent a counter-current supply that ensures that materno-fetal exchange is efficient and simply regulated.
[*] Concentration Gradient: the steeper the gradient, the more diffusion
[*] Barrier to diffusion: placental membrane gradually thins throughout pregnancy as the demand of the fetus increases
[*] Diffusion distance: haemochorial.
The placenta represents a selective barrier to the fetal circulation that regulates access to the fetal circulation and affords considerable protection from harmful agents. However, this barrier is not complete and can be breached either by simple “leakage” or a number of infectious agents may utilise existing transport systems (e.g. HIV), active penetrate (e.g. Treponema) or opportunistically exploit gaps in the epithelium (e.g. Toxoplasma).
List some teratogens and organisms that can cross the placenta
Teratogens can access the fetus via the placenta, giving physiological consequences. Teratogens are particularly damaging during critical stages of development
[*] Thalidomide
[*] Alcohol
[*] Therapeutic drugs particularly anticonvulsants
[*] Drugs of abuse
[*] Maternal smoking
Some pathogens are also able to cross the placenta:
[*] Varicella zoster
[*] Cytomegalovirus
[*] Treponema pallidum
[*] Toxoplasma gondii
[*] Rubella (=> microcephaly, patent ductus arteriosus and cataracts)
In addition to nutrient supply and waste removal, the placenta is responsible for the endocrine support of pregnancy and the provision of passive immunity that affoirds immune protection in the neonatal period.
Things can also go wrong due to unintentional outcomes from physiological processes.
Name molecules that travel across the placenta by simple diffusion, facilitated diffusion and active transport
Simple Diffusion: molecules moving down a concentration gradient
[*] Water
[*] Electrolytes
[*] Urea and uric acid
[*] Gases
Flow-limited, not diffusion-limited (dependent on optimum flow in uteroplacental circulation)
Fetal O2 stores are small – maintenance of adequate flow is essential
At term ~300 ml in maternal lakes
Facilitated Diffusion
[*] Glucose
Active Transport: specific transporters are expressed by the syncytiotrophoblast
[*] Amino acids
[*] Iron
[*] Vitamins
Describe the function of the placenta as a provider of passive maternal immunity to the neonate
Passive Immunity: immunological competence begins to develop late in the first trimester, by which time the fetus makes all of the components of complement.
Fetal immunoglobulins consist almost entirely of maternal immunoglobulin (IgG), which begins to be transported from mother to fetus at approximately 14 weeks. (immunoglobulin class-specific)
[*] The IgG is transported via Receptor Mediated Pinocytosis. This process matures as pregnancy progresses.
[*] Eventually the concentration of IgG in fetal plasma exceeds that of maternal plasma
[*] In this manner, the fetus gains passive immunity against various infectious diseases. Newborns produce their own IgG, but adult levels are not attained until the age of 3.
Describe the maternal Cardiovascular changes that occur during pregnancy
[*] As pregnancy advances, the fetal-placental unit’s increasing need for nutrition is met via maternal vascular-neogenesis. This is accommodated by changes in function of the maternal baro- and volume receptors.
[*] There is also increased blood flow to the growing breasts, kidneys and GI tract (increased metabolism).
[*] Plasma (blood) volume increases (but this increase isn’t matched exactly by increase in Hb => physiological anaemia (not pathological) whilst peripheral vascular resistance often falls during pregnancy.
- Increased volume leads to auscultatory systolic murmurs.
- Diaphragm moves up => displacement of the apex beat, changes on ECG.
- These changes are physiological NOT pathological
[*] Cardiac output increases
[*] Stroke volume increases
[*] Heart rate increases
[*] NB: CO = HR x SV
[*] Systolic BP is never increased in pregnancy (normally) – due to decrease in systematic vascular resistance. This can mask pre-existing hypertension.
Describe the changes in the Respiratory System during pregnancy
[*] Anatomical changes
- Diaphragm is displaced
- AP and transverse diameters of thorax increase.
[*] O2 consumption increases 20%
[*] Decreased functional residual capacity
[*] Vital capacity unchanged (increase in tidal volume is balanced by decrease in functional residual capacity)
[*] Pulmonary function is not impaired by pregnancy but diseases of the respiratory system may be more serious in pregnancy largely due to the increased oxygen requirement of gestation.
[*] The respiratory rate is little changed but tidal volume and oxygen uptake increase appreciably.
[*] Alveolar ventilation rate increased (due to increased tidal volume) but no change in respiratory rate
[*] Respiratory minute volume increased
[*] An increased awareness of the desire to breathe is common in pregnancy (physiological hyperventilation driven by progesterone), and may be interpreted as dyspnoea. The mechanism is felt to be the increase in tidal volume that lowers the pCO2 (so the mother can blow off the extra CO2 the fetus metabolically produces).
[*] This leads to respiratory alkalosis initially, which the kidneys compensate for by producing and reabsorbing less bicarbonate => reduced buffering capacity => greater predisposition to metabolic acidosis.
[*] The increased respiratory effort and the reduction in pCO2 are induced by progesterone acting directly on the respiratory centre and sensitizing chemoreceptors to CO2 changes.
Describe changes in Renal Function (Urinary System)
[*] Increased renal plasma flow, raises the glomerular filtration rate to ~55% of normal (increased secretion of renin, aldosterone and angiotensin II compensate for the expected sodium loss).
- Mechanism unclear but progesterone has been implicated
- Renal plasma flow increases more than GFR up to T3, so you get a decreased filtration fraction up to T3.
[*] Filtration capacity intact
[*] Functional renal reserve decreases as GFR increases (the system is stretched to its capacity).
[*] Urinary system: progesterone relaxes the smooth muscle in the walls of the ureters, which can result in stasis, hydroureter, UTIs and pyelonephritis. Urinary stasis could also lead to obstruction.
- Pyelonephritis can induce pre-term labour.
[*] Note it is important to know normal-for-pregnancy range for urea and creatinine because standard ‘normal’ levels could be an indication for significant renal impairment.
