Module 2 Flashcards
Describe the pathogphysiology of preeclampsia
The spiral arteries fail to remodel properly and so remain narrow, resulting in high pressure, poor flow vessels. This promotes clotting within the arteries, restricting blood flow to the placenta. During this time the oxygen tension of the placenta decreases, and when the clot is thrombolysed and flow is restored, oxygen tension increases again, which causes production of oxygen free radicals.
The oxidative stress damages the sycitiotrophoblast layer, causing release of suncytiotrophoblast microparticles into maternal circulation. This leads to endothelial damage and dysfunction, which causes hypertension, proteinuria, oedema, and increased coagulability
What is the standard clinical definition of preeclampsia?
Hypertension (>140/90) with proteinuria (>0.5g protein/ day on 2 or more separate occasions) during or just after pregnancy (just after is very rare)
Which feature of platelets might indicate preeclampsia?
Decreased number
Increased size
What change in maternal T-cells helps promote tolerance?
Increase in Th2 cells instead of Th1
Th2 cells are involved in the antibody-mediated immune response, and most antibodies an’t cross the placenta
This makes pregnant women more susceptible to viruses, which are tackled by Th1 mediated immune responses
What do trophoblasts express to avoid apoptosis by uterine NK cells?
HLA E and G
What do trophoblasts express to kill invading lymphocytes?
Fas ligand
What is fetal inflammatory response syndrome?
It’s defined by a rise in fetal plasma IL-6 in response to infection, and leads to systemic inflammation and a rise in fetal cortisol. this can lead to chronic lung disease, periventricular leukomalacia, and intraventricular haemorrhage
Which cells release progesterone to provide a chemotactic gradient for sperm?
Cumulus granulosa cells
Give three important functions of the zona pellucida
Prevent polyspermy
Enable acrosome reaction
Enable secondary binding events
Which glycoprotein receptor in the zona pellucida induces the acrosome reaction?
ZP3
How is the acrosome reaction initiated?
The sperm’s ZP3 receptors bind to the zona pellucida, triggering opening of T-type calcium channels. Intracellular calcium increases, activating the PLC messenger system which causes further calcium influx through TRPC2. This triggers the acrosome membrane to fuse with the sperm plasma membrane and release its contents.
How is the oocyte activated after the acrosome reaction?
PLC zeta is released from the sperm and activates IP3 signalling pathway in the oocyte. This leads to calcium oscillations from the endoplasmic reticulum, which activate the oocyte
What is the effect of cortical granule release into the perivitelline space?
The granules contain enzymes which cleave ZP glycoproteins (particularly ZP2) and cause cross-linkage of tyrosine rsidues to harden the zona pelludica and prevent polyspermy
How does fertilisation release the oocyte from meiosis II arrest?
The calcium oscillations activate APC (anaphase promoting complex) which degrades cyclin B (forms mature-promoting complex which holds the cell in arrest) and allows progression to anaphase. This is when the second polar body is made
Why is mitochondrial DNA only inherited from the mother?
Because mitochondrial DNA is held within the mitochondria. The paternal mitochondria are lost with the rest of the sperm tail
