Gestational hypertension

Introduction Pregnancy-induced hypertension syndrome (pregnancy-induced hypertension) is a common disease that seriously affects maternal and child safety. Increasing prenatal care and treatment can significantly reduce maternal mortality caused by pregnancy-induced hypertension. Among the 7 485 maternal deaths in selected areas in China from 1984 to 1988, the top 5 major causes of death were obstetric hemorrhage, heart disease, pregnancy-induced hypertension, amniotic fluid embolism, and puerperal infection. Prevention and treatment of pregnancy-induced hypertension is extremely important.

Cause

The exact cause of pregnancy-induced hypertension has not yet been fully understood. Therefore, effective preventive measures are still lacking. It is always an important issue in the field of obstetrics. The development of basic medicine has promoted the deepening of research in this area. And made promising progress. Many scholars at home and abroad have conducted many observations, researches and explorations, and put forward various theories such as immunology, uterus-placental ischemia theory, genetic theory, vasoactive substance imbalance, coagulation system and fibrinolysis system imbalance. The theory, lack of calcium and other, but only can explain some of the mechanisms, it is believed that pregnancy-induced hypertension is the result of a combination of multiple factors.

Immunology

Pregnancy is a complex physiological process. From an immunological point of view, similar to an organ transplant, an embryo with a parental allogeneic antigen is a graft to the mother, which is recognized by the maternal immune system and produces an immune response. However, in terms of its outcome, unlike organ transplantation, the mother has a protective immune response to the fetus until the fetus is delivered. It is conceivable that once the balance between the mother and the fetus is out of balance, the allogeneic embryonic antigen will be rejected and cause clinical pathological pregnancy, such as abortion, infertility, pregnancy-induced hypertension, premature delivery, low birth weight and the like.

2. Placental or trophoblastic ischemia theory

(1) Expression of trophoblastic adhesion molecules and pregnancy-induced hypertension: The growth of fetal-placenta depends mainly on the differentiation of cytotrophoblast (CTB) and the construction of uterine placental vascular network. CTB can form syncytiotrophoblasts and mesenchymal trophoblasts (ie, extravillous trophoblasts). CTB differentiates into free villi and fixed villi during early pregnancy. The former is directly immersed in the interstitial space, and carries out nutrient and gas exchange with the maternal blood. The latter proliferates and breaks through the basal layer of the endometrium, and becomes a mesenchymal trophoblast infiltrating the aponeurosis, muscle layer and blood vessels. In early pregnancy, the vascular infiltration only reaches the aponeurosis layer, and in the second trimester, the infiltration reaches 1/3 of the superficial muscle layer. During the late pregnancy, the trophoblast cells are dispersed in the local aponeurosis, muscle layer and vascular area. Interstitial trophoblasts gradually replace vascular endothelial cells along the spiral arterioles, deep into the blood vessel wall, degrade vascular smooth muscle and elastic fibers, expand the vascular lumen, reduce blood flow resistance, and increase blood flow. This process is called revascularization. The biological behavior of CTIS adhesion and adhesion to the surface of the aponeurosis, retrograde metastasis along the vascular endothelium and interstitial infiltration of the decidua is related to its cell adhesion molecule (CAM) phenotype (CAM is a widespread distribution). Glycoprotein on the cell surface and extracellular matrix.

It is divided into four major families: the integrin family, the calmodulin family, the selectin family, and the immunoglobulin superfamily). For example, the infiltrating cell surface expresses integrin 1, 5, and 1, while the adhesion-type integrin phenotype is 6 and 4. During the whole embryo implantation and placenta formation process, the phenotype of trophoblastic adhesion molecules will be converted accordingly. Once the phenotypic transition is impeded, it can lead to impaired trophoblast infiltration and shallow implantation. There is a significant obstacle to the CTB adhesion phenotype conversion pattern in placenta of patients with pregnancy induced hypertension. Integrin 64, 6v6 and E-calmodulin have high expression levels; however, they lack expression of v3, 11, VE-calmodulin, vascular adhesion molecules and platelet adhesion molecules; thus, the adhesion phenotype cannot be completed, and the epithelial surface cannot be obtained. Type fitting forms a vascular endothelium phenotype and obtains an infiltrating phenotype, which leads to obstruction of CTB differentiation and infiltration, and can not infiltrate the decidua, muscular layer and spiral arterioles, resulting in poor growth of placental vascular network, resulting in placental shallow implantation and placental ischemia. Pathological changes in hypoxia.

The exact mechanism by which CTB regulates the expression of CAM is not fully understood. In vitro culture CTB infiltration experimental model suggests that hypoxic tension can inhibit CTB in vitro infiltration by regulating the CTB adhesion phenotype. Pijnenbong et al found that CTB in patients with PIH has its own inherent defects, making it unable to express integrin molecules with glass mucin and fibronectin as ligands. Irving et al believe that the regulation of CTB expression of CAM is mainly affected by some cell growth factors in the autocrine and paracrine processes of CTB. Such as epidermal growth factor, insulin-like growth factor, transforming growth factor and the like. In addition, some inflammatory cytokines such as TNF-, IL-1, IL-1 can also affect CTB expression of CAM.

(2) vascular endothelial growth factor and pregnancy-induced hypertension: vascular endothelial growth factor (VEGF) is a secretory glycosylated polypeptide factor with strong pro-angiogenic growth and increased microvascular permeability. A specific endothelial cell mitogen is an important factor in the formation of physiological angiogenesis in humans. The placenta is an organ filled with vascular networks, and VEGF plays an important role in the development of placental blood vessels.

Experiments have shown that VEGF plays a role in all stages of pregnancy. In early pregnancy, VEGF is associated with placental neovascularization and trophoblast differentiation and infiltration. During middle and late pregnancy, there may be a role in reducing blood flow resistance, improving local vascular permeability, and enhancing substance exchange. The VEGF of human placenta is mainly distributed in cytotrophoblasts, syncytiotrophoblast cells, vascular endothelial cells and villous mesenchymal cells. VEGF is mainly secreted by syncytiotrophoblasts in the placenta, which can affect the formation of placental vascular network and the differentiation and infiltration of trophoblast cells. Zhang Wei and Liu Xia confirmed that during pregnancy-induced hypertension, VEGF secretion and placental vascular density in placental villus trophoblasts were significantly reduced, and were closely related to the severity of the disease. The main role of VEGF is to promote angiogenesis and improve blood supply. In the process of angiogenesis, there is often a synergistic effect of multiple angiogenic factors, but only VEGF acts specifically on endothelial cells. The placenta is an organ filled with vascular networks, and VEGF plays an important role in the development of placental blood vessels and fetal growth. Down-regulation of VEGF expression may cause changes in placental vascular construction, decreased placental vascular area, and affect blood supply to the placenta. Decreased VEGF levels indicate that it affects the differentiation and proliferation of trophoblasts, causing trophoblastic invasion and dysfunction, thereby affecting the physiological changes of the spiral arterioles, leading to the occurrence of pregnancy-induced hypertension.

(3) Placental growth factor and pregnancy-induced hypertension: placental growth factor (PLGF) is one of the members of the VEGF family. It is mainly expressed in placental tissue, and three kinds of isomers such as PLGF-1, PLGF-2 and PLGF-3 have been found. Its gene is located in the q24~q31 region of human chromosome 14, and can play a biological role by specifically binding to the tyrosine kinase receptor (FLT-1) on the cell surface. PLGF not only induces migration and activation of vascular endothelial proliferation, but also regulates the proliferation of trophoblast cells. In vitro culture found that trophoblast cells can express PLGF receptor. PLGF localizes the function of endothelial cells and trophoblasts in the placenta by autocrine and paracrine means. Hypoxia inhibits the secretion of PLGF in trophoblast cells.

3. Renin-angiotensin system (RAS)

(1) Renin gene and pregnancy-induced hypertension: Renin is the rate-limiting enzyme in RAS, and its function is to convert angiotensinogen (AGT) into angiotensin I (AngI). Animal experiments found that renin fragment restriction polymorphisms (RFLP) are associated with hypertension. However, Arngrimsson et al. showed that there was no statistical difference in RFPL between patients with pregnancy-induced hypertension and their spouses. It is speculated that there is no correlation between renin gene RFLP and pregnancy-induced hypertension.

(2) Renin-angiotensin system (RAS): RAS is a hormone endocrine system that plays an important role in the regulation of cardiovascular function and water and salt balance. Angiotensin II receptor (ATR) is an effector of RAS, mediates the physiological effects of angiotensin II (Ang II), and is a key link in the action of RAS. It plays a role in regulating blood pressure, fluid balance and vascular recasting. Important role. AGT is the precursor of AngII. The AGT molecule has two amino acid types at position 235: methionine (Met235) and threonine (Thr235), of which the Thr235 type AGT is closely related to the occurrence of essential hypertension.

(3) Angiotensin-converting enzyme gene access/deletion polymorphism and pregnancy-induced hypertension: In RAS, ACE is a key enzyme that converts AngI into a physiologically active AngII, and also has a vasodilator, bradykinin. The role of inactivation plays an important role in the physiological regulation of blood vessels. There was a significant correlation between ACE concentration and its genetic polymorphism. The insertion/deletion (I/D) polymorphism of an ALU sequence containing the 16th factor of the gene affects its transcription rate. When the Alu repeat (insertion type, type II) is present, the ACE gene transcription rate is decreased, thereby reducing the synthesis. Among the three genotypes of ACE gene (II, DD, I/D), the average level of DD type ACE was the highest, followed by I/D type, and type II was the lowest. Zhou Ning, Zhu Mingwei, Wu Yanyi, Shang Tao et al. The frequency and concentration of ACE genotypes in patients with pregnancy-induced hypertension and normal pregnancy were detected. It was found that DD>I/D>II, indicating DD or D-type alleles. The gene is dominant in pregnant women with pregnancy-induced hypertension, suggesting that the deletion polymorphism of ACE gene is associated with the occurrence of pregnancy-induced hypertension. The D allele is a susceptibility gene for pregnancy-induced hypertension, probably because the gene controls plasma and intracellular Caused by ACE expression. DD type has high plasma concentration, AngII production increases, and bradykinin degradation causes epoprostenol (prostacyclin) and prostaglandin E2 (PGE2) synthesis disorder, but the synthesis of thromboxane A2 (TXA2) is not reduced, resulting in PGI2 /TXA2 ratio decreased, peripheral vascular resistance increased, abnormal blood coagulation, fetal-placental blood flow decreased, prompting pregnancy-induced hypertension. Huang Yanyi and other research results are opposite. The ACE gene is mainly type II in patients with pregnancy-induced hypertension, which may be related to different types of pregnancy-induced hypertension. Different types and different clinical manifestations of pregnancy-induced hypertension may also have different types of gene expression.

(4) Angiotensin I, type II receptors and pregnancy-induced hypertension: the sensitivity of blood vessels to AngII increases during pregnancy-induced hypertension, and the mechanism may be related to the reduction of vasodilator activity and the type, number and affinity of peripheral blood vessel ATR. Change related. ATR is classified into type 2, and only one type of ATR (angiotensin I receptor, AT-1) is currently found in humans and higher mammals. Because AT-1 mediates the main biological role of AngII, the study of ATR gene mainly focuses on the AT-1 gene polymorphism. Bnnardeaux et al. used PCR to amplify all the coding regions and 3 untranslated regions of AT-1 gene in 60 patients with family-susceptible hypertension, and combined with single-strand conformation polymorphism, five polymorphic loci were detected (T637 C, A1062G, A1166C, G1517T and A1878G), only the C allele frequency of the 1166 polymorphic locus in the 3 region was significantly increased in patients with a family history of hypertension, suggesting AT- The frequency of alleles of the 1 gene A1166 polymorphic locus was significantly associated with essential hypertension. Hu Yuhong, Shang Tao and other studies found that the nucleotide variation of the A1166 locus in the AT-1 gene was significantly associated with pregnancy-induced hypertension. The frequency of polymorphic variant allele C of AT-1 gene A1166 in patients with pregnancy-induced hypertension increased significantly, and the frequency of genotype AC and CC was significantly higher than that of normal pregnancy group, suggesting polymorphism of A1166 locus and pregnancy of AT-1 gene. High bloody disease is related. It has been found that patients with pregnancy-induced hypertension and normal pregnancy and fetal AT-1 three allele polymorphisms (573CT, 1062AG, A116C) and AT-1 gene 3 dinucleotide repeats (CA There is no significant difference in the frequency of n polymorphism mutations, but A4 and 573T in the alleles of the dinucleotide repeat sequence in patients with pregnancy-induced hypertension. The frequency of allele maternal delivery was significantly higher than that of normal pregnancy, and there was partial linkage disequilibrium between A4 and 573T. It is suggested that the variation of A4 and 573T alleles may reduce the expression of AT-1, affecting placental formation, placental PGI2 secretion and placenta. Hemodynamics.

(5) Prostaglandins and pregnancy-induced hypertension: There are two groups of prostaglandins and obstetrics, PGE2/PGF2 and PGI2/TXA2, which are 4 to 8 times stronger than the former. PGE2 and PGI2 have anti-AngII vasoconstriction, which causes vasodilation, and PGF2 and TXA2 have vasoconstriction, and the two form a balance. TXA2 also activates platelets to cause platelet aggregation and thrombosis. If the two are not coordinated, pathological damage can be caused. The results showed that the levels of PGE2 and PGI2 in the placenta and urine were low in patients with PIH, while the levels of PGF2 and TXB2 (the metabolites of TXA2) were significantly increased. The ratio of PGE2/PGF2 and PGI2/TXA2 was significantly lower than that of normal pregnant women.

an examination

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Diagnosis can be made based on medical history, clinical manifestations, and auxiliary examinations.

Pregnancy hypertension BP140/90mmHg, first appeared in pregnancy, and returned to normal at 12 weeks postpartum, urine protein (-); patients may be associated with upper abdominal discomfort or thrombocytopenia, can be diagnosed after birth.

Mild BP140/90mmHg in preeclampsia, 20 weeks after pregnancy; urine protein300mg/24h or (+). May be associated with symptoms such as upper abdominal discomfort and headache.

Severe BP160/110mmHg, urine protein2.0g/24h or (++), serum creatinine>106mol/L, platelet<100×109 /L, microangiopathic hemolysis (increased blood LDH), serum ALT or AST Elevation, persistent headache or other cranial nerves or visual disturbances, persistent upper abdominal discomfort.

Chronic hypertension complicated with pre-eclampsia hypertension pregnant women without urine protein before 20 weeks of pregnancy, if there is urine protein 300mg / 24h; high blood pressure pregnant women 20 weeks before pregnancy, sudden increase in urine protein, blood pressure is further increased or platelets <100 × 109 / L.

Pregnancy with chronic hypertension BP140/90mmHg, pre-pregnancy or 20 weeks before pregnancy or 20 weeks after pregnancy, the first diagnosis of hypertension and continued until 12 weeks postpartum.

Differential diagnosis

1. Essential hypertension or chronic hypertension

There is a family history, mainly showing elevated blood pressure, which usually occurs before the 20th week of pregnancy, general edema and proteinuria, often no symptoms, urine routine microscopic examination generally no red blood cells and cast. Renal function tests were normal in early pregnancy, especially if uric acid levels were not elevated. The fundus is characterized by arterial thinning, arteriovenous cross-pressure, and hypertensive lesions with small arteriosclerosis. Although postpartum blood pressure can be reduced, it can only be restored to pre-pregnancy levels. Patients with pregnancy-induced hypertension have normal blood pressure before 20 weeks of gestation, and blood pressure rises after 20 weeks of gestation. It is often accompanied by varying degrees of edema, headache, dizziness, chest discomfort and proteinuria. In severe cases, tubular and blood may appear in the urine. Uric acid is elevated, and the fundus examination is a small arterial spasm. In severe cases, hemorrhagic exudation or retinal exfoliation may occur. These lesions gradually recover more than postpartum. Patients with essential hypertension with pregnancy-induced hypertension should be determined according to the history and the time and extent of blood pressure elevation. Patients with primary hypertension are prone to pregnancy-induced hypertension, and the time to develop pregnancy-induced hypertension is earlier than that of normal pregnant women.

2. Chronic nephritis

There is a history of acute and chronic nephritis before pregnancy, and there are varying degrees of edema and proteinuria and hypertension before pregnancy. These symptoms can be aggravated during pregnancy, and more often appear before 20 weeks of gestation. Severe cases can be found to have tubular and renal dysfunction, persistent high blood pressure, and fundus examination may have nephritic retinopathy. Occult nephritis is difficult to identify, and the medical history should be carefully asked. If necessary, further examination of glomerular and renal tubular function should be performed. The pregnancy-induced hypertension syndrome occurred after 20 weeks of gestation, and the amount of proteinuria was variable, accompanied by varying degrees of edema. In severe cases, there may be a cast in the urine and an increase in blood uric acid. The incidence of pregnancy-induced hypertension in patients with chronic nephritis increases, and the time of occurrence is early, the symptoms are severe, and the mortality rate of perinatal and maternal women is high.

3. Differential diagnosis of eclampsia

(1) Epilepsy: Epilepsy is a group of chronic diseases characterized by transient central nervous system dysfunction caused by recurrent episodes of abnormal neuronal discharge. It is a transient brain dysfunction, so there is a similar history of seizures before pregnancy. In the case of a large episode, the muscles of the whole body are continuously contracted. The convulsions are lost for a few seconds, and the EEG indicates epileptic discharge waves. If the patient does not have pregnancy-induced hypertension, it is generally not associated with elevated blood pressure, edema, and proteinuria. Epilepsy can occur at any time during pregnancy, and eclampsia occurs more often after 20 weeks of gestation. There are many clinical manifestations of severe pregnancy-induced hypertension before the onset, and the time of convulsion is longer.

(2) snoring: snoring convulsions often have certain emotional stimuli, when others are present, they are ill, conscious, convulsions have no regularity, most of them have no big or urinary incontinence. After the event, the episodes can still be recalled, and the nervous system and EEG are normal.

(3) subarachnoid hemorrhage: can occur at any stage of pregnancy, severe headache, accompanied by nausea and vomiting, obvious symptoms of increased intracranial pressure, CT and cerebrospinal fluid examination can be found subarachnoid hemorrhage, but not accompanied by pregnancy-induced hypertension No high blood pressure, edema and proteinuria. Diagnosis can be made based on medical history, clinical manifestations, and auxiliary examinations.

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