Week 3 Flashcards

1
Q

What are the changes in the inflammatory state of the woman throughout the pregnancy? Why?

A

First Trimester: Pro-inflammatory state; promote implantation
Second Trimester: Anti-inflammatory state; fetal growth
Third Trimester: Pro-inflammatory; promote labor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the inflammatory state in the first trimester of pregnancy and how specific immune cells work throughout this period of pregnancy?

A

During the first trimester of pregnancy, there is a pro-inflammatory state. The blastocyst needs to attach to the endometrial wall of the placenta for the fetus to be fully implanted in the placenta. In order for that to happen, dendritic cells secrete factors that remove the mucin layer which normally covers the endometrial wall of the placenta to uncover the molecules to which the blastocyst will bind to. Dendritic cells will also secrete signals which increase the likelihood of implantation. Lastly, immune infiltrates (macrophages, NK cells) will also rush to the site of implantation to promote tolerance of the fetus.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are Th1 cells? What do they do? When are they released in the context of pregnancy?

A

Th1 cells are a subdivision of CD4 T-helper cells which produce pro-inflammatory cytokines. They’re released in the first and third trimesters of pregnancy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are Th2 cells? What do they do? When are they released in the context of pregnancy?

A

Th2 cells are a subdivision of CD4 T-helper cells which produce anti-inflammatory cytokines. They are not released in pregnancy, although the second trimester of pregnancy is said to move toward a Th2 environment because of the suppression of Th1 cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are T-reg cells? What do they do? When are they released in the context of pregnancy?

A

T-reg cells are a subdivision of CD4 T-helper cells which produce anti-inflammatory action and promote immune tolerance. They also suppress the action of Th1 cells. They are released in the second trimester of pregnancy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What type of T helper cell would you expect to see released during infection which could be detrimental to pregnancy?

A

Th1 cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the necessary actions of the following cells during the second trimester of pregnancy and describe their importance in the development of the pregnancy. Macrophages, T-reg, NK?

A

Macrophages: Release anti-inflammatory cytokines to move toward a Th2 environment, and phagocytose any dying cells of trophoblast. This is crucial as it prevents the release paternal antigens which would trigger maternal immune response against the fetus
T-reg: Protect fetus against rejection by promoting immune tolerance, as well as maintain anti-inflammatory (Th2) environment
NK: Recognize non-self-antigens, induce T-reg cells, and interact with macrophages.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What would be the result of a switch from a Th2 to a Th1 environment during the second trimester of pregnancy?

A

It could result in miscarriage or preterm birth.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the pro-inflammatory state required during the third trimester of pregnancy? Why is it necessary?

A

The pro-inflammatory state during the third trimester of pregnancy is necessary to allow labour to occur. The influx of immune cells into the muscular wall of the uterus promotes contractions and separations of the placenta.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are some (non T-helper cell) immune changes that occur during pregnancy?

A

There is a relative decrease in the concentrations of B cells because of pregnancy hormones. There is also a decrease of antibody levels due to hemodilution.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the effect of women’s adapted immune system during pregnancy when catching influenza?

A

While pregnant women are not at an increased risk of infection, they are at risk for more severe disease in the late pregnancy compared to non-pregnant women. More likely to be caused due to anatomical and physiological changes rather than altered immune response.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the fetal consequences of catching maternal influenza?

A
  • Preterm delivery
  • Stillbirth
  • Small for gestational age
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is a way to increase prevention from maternal influenza?

A

Influenza vaccine once pregnant.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

List infections which are associated with being more severe in pregnant women? Why?

A

Listeria: Higher risk of disseminated disease, associated with miscarriage and stillbirth. Placenta is thought to act as a reservoir allowing uncontrolled spread
Hepatitis E: Higher incidence, increased rates of fulminant hepatitis and death. Possibly due to the increased replication of the virus due to estradiol
Malaria: Higher incidence of severe malaria, possibly due to trophism of parasites for placental tissue.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the reason behind women being more prone to catching certain disease/developing worst effects of the disease while pregnant?

A

Two reasons: Adapted immune system throughout pregnancy (not immunosuppression) as well as physiological and anatomical changes of pregnancy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the process of maternal-fetal IgG transfer?

A

The placenta has a layer of specialized cells called syncytotrophoblasts. Maternal IgGs pass through this layer through active transfer into the stroma of the placenta using specialized receptors called FcRn. From the stroma, they are then taken up into the fetal endothelium.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the proportion of fetal IgGs as a proportion of the mother’s at birth?

A

Oftentimes the baby’s IgG concentrations are higher than the mother’s (>100%) due to the maternal-fetal IgG transfer during gestation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why is the transfer of IgGs from the mother to the fetus so important?

A

It provides the baby with protection from certain diseases during the first few months of life while as it creates its own IgGs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why was there a period in which pertussis was occurring at very high rates in infants between 2011 and 2012? What did they do to solve that?

A

Whooping cough was endemic in the infant population between 2011 and 2012 due to many of the mothers having had vaccination for it in their own childhood. Over time, their own IgG concentrations against pertussis faded, which as a result, meant that their own babies were receiving very low, if any IgGs against pertussis through maternal IgG transfer. This left them at risk of catching it in the first weeks of life.
In order to fight this phenomenon, pertussis vaccination in pregnancy started becoming recommended in 2012 in order to get an immune response which creates IgGs against pertussis, and by association, protect the baby through maternal IgG transfer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How many week is human gestation?

A

38 weeks from conception

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the main relaxant and stimulatory hormones of the uterus?

A

Progesterone is the main relaxant while estrogen is the main stimulatory hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

During pregnancy, what hormone is mostly dominating the uterus?

A

Progesterone – keeps the uterus in a relaxed state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does progesterone act as a relaxant during pregnancy?

A

Progesterone hyperpolarizes myometrial cells, making them unable to contract, as well as inhibiting prostaglandin synthesis.

24
Q

How does the hormonal profile of the uterus shift from during pregnancy to during labor?

A

During pregnancy, the hormones dominating the uterus are relaxant hormones – notably progesterone. During labor however, there is a large shift which causes estrogen to rise and progesterone to be lowered.

25
What are prostaglandins? What produces prostaglandins, and what is their role in labor?
Prostaglandins are factors found in the body and in the scope of labor, they are produced by fetal membranes as well as the maternal uterine tissue. There are two main prostaglandins in the scope of labor called PG2-a and PGE-2. These are stimulated by estrogen, and their function is to potentiate the contractions caused by oxytocin in paracrine cells, as well as ripen the cervix in the induction of labor.
26
What is oxytocin and describe its role in labor? Where is it produced?
Oxytocin is a hormone produced around the body and is especially present in the uterus during labor. It is produced by the fetal and maternal posterior pituitary glands. Its function is to stimulate muscle cells to contract as well as to stimulate PGF-2 production.
27
What non-hormonal factors also affect the length of gestation?
``` Uterine distension (e.g. if there are twins, uterus is more stretched and therefore bigger chance for lower gestation period Placental insufficiency ```
28
What is meant by cervical ripening? What factors allow that to happen?
Cervical ripening refers to the process of change that the cervix undergoes prior to delivery as a way to ensure that it is dilated enough to ensure a successful delivery. The cervical ripening is essentially a move from the stiff collagen to the elastic elastin that make up the wall of the cervix. This change in cervical makeup is made through the use of prostaglandins, protases, as well as relaxin.
29
What is the conclusion of labor?
Delivery of the baby and placenta.
30
How many stages does labor have?
3 unequal stages (and one preceding stage)
31
Describe the stage 0 of labor?
Pre-labor occurs 4-5 week before labor. This stage consists of a gradual change in the environment of the uterus, from dominated by progesterone, to gradually being dominated by estrogen. There is also a gradual increase in uterine activity which can lead to Braxton-Hicks contractions. There are also changes to the cervical consistency (collagen  elastin). Lastly, this is the period in which the fetus engages in the pelvic brim.
32
What is the first stage of labor? How long is it usually in first pregnancies?
Dilation stage; 8-14 hours
33
Describe the processes that happen during phase 1 of labor?
Latent phase: Cervical effacement; cervix shortens, as well as dilates to 3-4 cm. Active phase: Cervix fully effaced, and dilates at around 1 cm/hour to reach 10 cm There are also large contractions occurring at shorter and shorter intervals, as well as uterine myocytes progressively shortening through a process called brachystasis.
34
What is brachystasis?
A process which occurs to force the fetus out of the uterus, by which myocytes contract and relax repetitively. However, when the myocytes relax, they don’t get back to their original length, causing a progressive shortening of the muscle cells and therefore a loss of elasticity further pushing down on the baby.
35
What is the second stage of labor? How long does it usually last?
Expulsion stage. 1-5 hours.
36
Describe the processes that happen during phase 2 of labor?
The expulsion stage starts at the full dilation of the cervix to the delivery of the baby. The baby’s head must rotate 90 degrees, and the uterine contractions are aided by pushing from the mother at the time of contractions.
37
What is the third stage of labor? How long does it usually last?
Placental stage. 15 minutes.
38
Describe the processes that happen during phase 3 of labor?
Stage by which the placenta is delivered and marks the end of the labor.
39
Why is synthetic oxytocin often given to mothers after they have delivered the baby?
To cause uterine contraction as a way to deliver the placenta.
40
What triggers the process of labor?
The fetus will, in the days/weeks prior to birth, start producing more and more cortisol through its fetal HPA axis. The heightening cortisol concentrations will in turn cause the maturation of the fetal organs, as well as trigger the initiation of labor.
41
What is a key hormonal difference in the process of labor between humans and other species?
Progesterone levels in humans do not fall before labor whereas they do in other species. The effectiveness of progesterone might fall due to less receptors.
42
If the human fetus cannot convert progesterone to estrogen like other species, how is estrogen produced in the fetus?
The fetus will utilize a precursor – DHEA – either synthesized from the fetal adrenal/liver, or taken directly from the maternal adrenal and turn the DHEA to estrogen.
43
What is the role of placental corticotrophin releasing hormone in labor?
Placental CRH stimulates placental prostaglandin production, which, potentiate uterine contractions initiated by oxytocin. CRH is elevated In women who feel stressed and have predicted preterm labor.
44
What are the effects of the increase of estrogen prior to parturition?
Increases the amount of oxytocin receptors in the myometrium
45
What is Ferguson’s reflex?
Ferguson’s reflex is a positive feedback loop that occurs during labor. This positive feedback loop is initiated with the fetus’ head pushing against the cervix. This initiates the loop which causes two effects. The first one is the activation of prostaglandins, that potentiate the action of oxytocin, and therefore causes stronger contractions. Moreover, the engagement of the fetal head on the cervix also causes more oxytocin release, which in turn causes more contractions. The loop keeps going until the end of delivery.
46
Describe the mechanism by which there are coordinated contractions during the delivery of the baby?
The fundus of the uterus contains pacemaker cells. These cells are joined to non-pacemaker cells using gap junctions. These pacemaker cells undergo spontaneous action potentials, and these action potentials spread to non-pacemaker cells through gap junctions which allows the coordinated movement of the contractions through the uterus.
47
Describe the cellular mechanisms that cause myometrial cell contraction?
Prostaglandins and oxytocin bind to the cell receptor which releases the G-protein. The signal then causes calcium release from the sarcoplasmic reticulum, as well as the opening of ion channels which allow the entry of extracellular calcium into the cell. The massive influx of calcium causes the phosphorylation of myosin and in turn the binding to actin which causes the contraction.
48
How are prostaglandins produced?
Breakdown of arachidonic acid, making COX-1 or COX-2; which is then converted to prostaglandins using PG synthase.
49
How are prostaglandins used pharmacologically?
Dinoprostone, a naturally occurring PGE2 drug, is given to mimic the action of prostaglandins in the cervix, to induce cervical ripening.
50
What causes the release of oxytocin in the scope of labor?
Cervical dilation
51
How is oxytocin used pharmacologically?
Synthetic oxytocin is given to enhance the first stages of labor; used as a way to cause enhanced and increased uterine contractions. It is given through slow IV infusion.
52
What is the role of cortisol in fetal development?
Cortisol works to mature fetal organs. Allows for the development of surfactant after 24 weeks. It allows for the release of glucose stored in the liver when the baby is delivered, as well as helps to excrete waste products like bilirubin. Also has factors in kidney, adrenal, and pancreas maturation.
53
What is fetal distress? What causes it?
Fetal distress is hypoxemia of the fetuses and can be caused by a range of factors such as the following: - Reduced placental perfusion - Detached placenta - Prolapsed umbilical cord Fetus changes to anaerobic respiration which results in acidosis.
54
What are the most common problems for mothers during delivery which may necessitate Caesarian delivery?
- Malpresentation - Cephalopelvic disproportion
55
How is oxytocin used pharmacologically?
Synthetic