The cGMP then activates cGMP-dependent kinase or PKG (protein kinase G). Activated PKG promotes vasorelaxation (via a reduction of intracellular calcium levels), alters the expression of genes involved in smooth muscle cell contraction, migration and differentiation, and inhibits platelet activation. Nitric oxide–soluble guanylate cyclase signaling also leads to anti-inflammatory effects.Phosphodiesterase type 5 (PDE5), which is abundant in the pulmonary tissue, hydrolyzes the cyclic bond of cGMP. Consequently, the concentration of cGMP (and thus PKG activity) decreases. Endothelin
Endothelin-1 is a peptide (comprising 21 amino acids) that is produced in endothelial cells. It acts on the endothelin receptors ETA and ETB in various cell types including vascular smooth muscle cells and fibroblasts, leading to vasoconstriction, hypertrophy, proliferation, inflammation, and fibrosis. It also acts on ETB receptors in endothelial cells; this leads to the release of both vasoconstrictors and vasodilators from those cells, and clears endothelin-1 from the system. Prostacyclin (and thromboxane)
Prostacyclin is synthesized from arachidonic acid in endothelial cells. In vascular smooth muscle cells, prostacyclin binds mainly to the prostaglandin I receptor. This sends a signal to increase adenylate cyclase activity, which leads to increased synthesis of cyclic adenosine monophosphate (cAMP). This in turn leads to increased cAMP-dependent protein kinase or PKA (protein kinase A) activity, ultimately promoting vasodilation and inhibiting cell proliferation. Prostacyclin signaling also leads to anti-thrombotic, anti-fibrotic, and anti-inflammatory effects. Levels of cAMP (which mediates most of the biological effects of prostacyclin) are reduced by phosphodiesterases 3 and 4. The vasoconstrictor thromboxane is also synthesized from arachidonic acid.
Fetal-maternal haemorrhage is the loss of fetal blood cells into the maternal circulation. It takes place in normal pregnancies as well as when there are obstetric or trauma related complications to pregnancy. Normally the maternal circulation and the fetal circulation are kept from direct contact with each other, with gas and nutrient exchange taking place across a membrane in the placenta made of two layers, the syncytiotrophoblast and the cytotrophoblast. Fetal-maternal haemorrhage occurs when this membrane ceases to function as a barrier and fetal cells may come in contact with and enter the maternal vessels in the decidua/endometrium. Description
Normal pregnancy
It is estimated that less than 1ml of fetal blood is lost to the maternal circulation during normal labour in around 96% of normal deliveries. The loss of this small amount of blood may however be a sensitising event and stimulate antibody production to the foetal red blood cells, an example of which is Rhesus disease of the newborn. Abnormal pregnancy
Causes of increased foetal-maternal haemorrhage are seen as a result of trauma, placental abruption or may be spontaneous with no cause found. Up to 30ml of foetal-maternal transfusion may take place with no significant signs or symptoms seen in either mother or foetus. Loss in excess of this may result in significant morbidity and mortality to the fetus. Fetal-maternal haemorrhage is one cause of intrauterine death (IUD). Diagnosis
The Kleihauer–Betke test is a blood test used to measure the amount of foetal hemoglobin transferred from a foetus to its mothers bloodstream.