pregnancy-induced hypertension
Introduction
Introduction to pregnancy-induced hypertension syndrome Pregnancy-induced hypotension syndrome (PIH) is a disease unique to pregnancy. This disease occurs after 20 weeks of pregnancy. The clinical manifestations are hypertension, proteinuria, edema, and severe headache. Dizziness, vertigo and other symptoms, and even convulsions, coma, the current pregnancy-induced hypertension is still one of the main causes of pregnancy, maternal and fetal, infant death. basic knowledge Proportion of illness: 9% of pregnant women Susceptible population: pregnant women Mode of infection: non-infectious Complications: cerebral hemorrhage, subarachnoid hemorrhage, coma, acute heart failure, hemiplegia, placental abruption
Cause
Causes of pregnancy-induced hypertension syndrome
(1) Causes of the disease
The exact cause of pregnancy-induced hypertension has not yet been fully understood. Therefore, effective preventive measures are still lacking. The cause of the disease is always an important subject in the field of obstetrics. The development of basic medicine has promoted the deepening of research in this area and made gratifying progress. Over the years, many scholars at home and abroad have conducted various observations, researches and explorations, and proposed 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, but 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 imbalanced, the allogeneic embryonic antigen will be rejected and cause clinical pathology. Pregnancy, such as abortion, infertility, pregnancy-induced hypertension, premature delivery, low birth weight, etc. According to the current study, the factors causing the imbalance of immune balance are the most important in the following aspects.
(1) Correlation between pregnancy-induced hypertension and human leukocyte antigen:
1 With the deep understanding of the immune mechanism of transplantation, it is found that human leucocyte antigen (HLA) on the cell membrane plays a decisive role in tissue transplantation and rejection. HLA is a group of human short chromosomes on chromosome 6. A highly polymorphic, tightly linked group of genes encoding the major histocompatibility antigens that are central to specific immunity, and it has been shown that HLA not only controls allogeneic rejection, but also with immune responses to the body. Regulation is closely related to the production of certain pathological states. This antigen is further divided into two categories. Class I has ABC antigen and class II has DR antigen. In recent years, studies on trophoblastic cell antigens have revealed that chorionic trophoblast cells are HLA-I and Class II antigens are not expressed, but are highly expressed in non-villi trophoblast cells (ie, trophoblastic layers that infiltrate into the decidual layer of the uterus and even the superficial myometrium of the uterus and the endothelial layer of the spiral artery, which are in direct contact with maternal blood and uterine tissue). The HLA-I antigen is an HLA-G antigen, which may cause genetic information transmission in contact with the mother, so that the mother recognizes the embryonic allogeneic antigen early, Goldman- Wohl et al. used antigen hybridization to detect HLA-G expression in placental tissues of normal pregnant women and patients with pregnancy-induced hypertension. It was found that HLA-G was abundantly expressed in fixed extravillous trophoblast cells, and the expression increased with invasiveness. In the Gaozheng group, 9 cases of HLA-G expression were deficient or decreased compared with the normal group. It is speculated that the placental trophoblasts of pregnancy-induced hypertension are vulnerable to the maternal immune system due to the lack of expression of protective HLA-G [mainly decidual natural killing). The attack of cells (NK) and some cytotoxic cytokines cannot effectively invade the parental spiral artery, causing the velvety implantation to be too shallow. The poor vascular development leads to the obstruction of blood vessel recasting, and the formation of a placenta rich in blood flow.
2 Modern immunology believes that in organ transplantation, the greater the HLA compatibility between the donor and the recipient, the higher the success rate of transplantation, and the greater the HLA compatibility of the maternal fetus at the maternal-fetal interface, the less the mother can recognize the embryo. Antigen, can not produce blocking antibodies, embryos are not protected by blocking antibodies and are rejected, that is, pathological pregnancy, such as miscarriage, infertility, pregnancy-induced hypertension, premature delivery, etc., Hu Xing, Wu Ganyu, Liu Guocheng, etc. to study human leukocyte antigen Correlation with pregnancy-induced hypertension found that the frequency of HLA-DR4 antigen in the PIH group, the HLA-DR4 antigen sharing rate and the gene frequency of the allele 0405 were significantly higher than those in the control group. They considered the allele 0405 as the pregnancy-induced hypertension. Susceptible genes, which may be linked to the imbalance of the disease-causing gene of the pregnancy-induced hypertension, cause the immune system to disorder or directly act as an immune response gene to affect macrophage-presenting antigens through gene products such as antigens, or interact with other cells to cause maternal blood vessels. The damage of endothelial cells leads to the occurrence of pregnancy-induced hypertension, the sharing rate of HLA-DR between maternal and fetal is increased, the compatibility is increased, and the maternal ability to recognize fetal antigen is weak. Due to the lack of HLA-DR antigen stimulation of the maternal immune system, the mother can not produce the blocking antibody necessary for maintaining pregnancy, and on the one hand can not block the placental antigen component entering the mother body, forming immune complex deposition in the tissue to cause damage, On the other hand, because it can not bind to the surface antigen of placental trophoblast cells to block its antigen, so that it can no longer bind to the maternal cytotoxic antigen, and activate the immune phagocytic system T lymphocytes, causing cytotoxic damage, so the maternal and fetal HLA antigen phase The greater the capacity, the more likely it is to develop pregnancy-induced hypertension.
But there is also the opposite view, Wihon et al believe that pregnancy-induced hypertension has nothing to do with HLA.
(2) Immune nutrition/immune damage balance disorder: The response of the immune system to allogeneic antigens is mainly regulated by helper T cells (Th) and its cytokines. In the past, it was found that the ratio of Th inhibitory T cells (Ts) decreased in normal pregnant women. The ratio of Th/Ts in patients with pregnancy-induced hypertension has increased. The current study found that the key to normal maternal-fetal immune balance lies in the immune balance between Th1/Th2.
Th is divided into three subtypes according to the secreted cytokines: Th1 cells secrete interleukin 2,12 (IL-2, IL-12), interferon- (IFN-), tumor necrosis factor , (TNF-, ), promote cellular immunity; Th2 cells secrete interleukin 4,5,10,13 (IL-4, IL-5, IL-10, IL-13) to promote humoral immunity; Th0 cells secrete above Various factors, these cellular immune factors form an immunoregulatory network in an autocrine and/or paracrine form, regulate and control the production of the placental vascular bed and blood flow, and the production of various related immune factors.
In the immune system's response to allogeneic antigens, the Th1-type immune response is shown as immune killing, and the Th2-type immune response is shown as immune protection or immune nutrition. Saito et al found that the ratio of Th1:Th2 in normal pregnant women is higher in pregnancy and later. Normal non-pregnant women were low, while the percentage of Th1 cells and Th1:Th2 in peripheral blood of patients with pregnancy-induced hypertension were significantly higher than those in normal pregnant women. IL-12 in peripheral blood mononuclear cells (PBMCs) of patients with severe pregnancy-induced hypertension in vitro. The expression of TH was significantly higher than that of normal pregnant women, and the ratio of Th1/Th2 was positively correlated with the expression of IL-12. The secretion of TNF-, IL-2 and IFN- was higher than that of the latter, TNF-/IL-4. IL-2/IL-4, IFN-/IL-4 3 is also higher than the former, and the mean arterial pressure is related to the expression of Th1 type cytokines IL-2, IFN-, TNF-. Sexually, the secretion of Th2 type cytokines has a protective effect in patients with pregnancy-induced hypertension, and the increased expression of Th1 type cytokines with immune killing causes the imbalance of Th1/Th2 ratio, leading to the pathophysiology of pregnancy-induced hypertension.
(3) Effects of immune complexes: immune complex (IC) is a binding product of antigen-antibodies, which plays an indispensable role in the clearance and destruction of various antigens. There are about 100,000 nourishments per day during normal pregnancy. Leaf cells, which correspond to about 1g of tissue, enter the maternal circulation and form an immune complex with the maternal antibody, which is engulfed by the mother's mononuclear macrophage system. The trophoblast cells in the maternal blood of patients with pregnancy-induced hypertension increase, compared with normal pregnancy. Women are 20 times higher, and the immune complexes formed are significantly increased. After IC deposition in the glomerular basement membrane, glomerulonephritis-like changes occur through the corresponding immune response, which increases the permeability of the basement membrane and a large amount of protein is poured out. IC deposits in the decidual vascular wall of the uterus placenta, activates the complement system, causes inflammatory reaction through free active substances, causes vascular endothelial damage, placental blood flow disorder, fetal ischemia and hypoxia, and passed the test in 1999 by Shangguan Biwen. The plasma terminal complement complex (SC5b-9) in patients with pregnancy-induced hypertension is used to investigate the occurrence and development of pregnancy-induced hypertension. The results of SC5b-9 are significant in patients with pregnancy-induced hypertension and high risk factors for pregnancy-induced hypertension. Increased, SC5b-9 is a complex of complement-activated end product C5b-9 that binds to S protein in plasma, which binds to S protein receptors on cell membranes such as platelets, neutrophils, epithelial cells, and red blood cells. This leads to cell lysis, suggesting that IC may be involved in complement activation, increased SCSb-9 complex, toxic effects on systemic vascular endothelial cells, damage to vascular endothelium and multiple organ damage, eventually leading to pregnancy-induced hypertension.
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 mesenchytrophoblasts. (ie, extravillous trophoblast cells), CTB differentiates into free villi and fixed villi during early pregnancy. The former is directly immersed in the interstitial space, and exchanges nutrients and gases with maternal blood. The latter proliferates and breaks through the basal layer of the endometrium. Interstitial trophoblasts infiltrate the decidua, muscle layer and blood vessels. In early pregnancy, the vascular infiltration only reaches the aponeurosis layer. In the second trimester, the infiltration reaches 1/3 of the superficial layer. During the late pregnancy, the trophoblasts are dispersed in the local aponeurosis, the muscular layer and In the vascular region, the interstitial trophoblasts gradually replace the vascular endothelial cells along the spiral arterioles, deep into the blood vessel wall, degrade the vascular smooth muscle and elastic fibers, expand the vascular lumen, reduce blood flow resistance, and increase blood flow. This process is called Revascularization of the blood vessels, while CTIS adheres to the surface of the aponeurosis, attaches, reverses the vascular endothelium and invades the sacral membrane. It is related to its cell adhesion molecule (CAM) phenotype (CAM is a type of glycoprotein widely distributed on the cell surface and extracellular matrix, which is divided into four major families: integrin family, calmodulin family, selectin Family and immunoglobulin superfamily), for example, infiltrating cell surface expressing integrin 1, 5 and 1, while adhesion-type integrin phenotype is 6 and 4, nourishing throughout embryo implantation and placenta formation The phenotype of cell adhesion molecules will be converted accordingly. Once the phenotypic transformation disorder, the trophoblastic infiltration ability may be impaired and shallow implantation. The CTB adhesion phenotype conversion pattern of placenta in patients with pregnancy-induced hypertension has obvious obstacles. Integrin The expression levels of 64, 6v6 and E-calmodulin are high; however, the expressions of v3, 11, VE-calmodulin, vascular adhesion molecules and platelet adhesion molecules are lacking; thus, the transition of adhesion phenotype cannot be completed and cannot be determined by epithelial phenotype. Forming a vascular endothelial phenotype and obtaining an infiltrating phenotype, resulting in obstruction of CTB differentiation and infiltration, infiltration of the decidua, muscle layer and spiral arterioles, so that the growth of the placental vascular network is not Good, causing placental shallow implantation and placental ischemia, pathological changes of hypoxia.
At present, the exact mechanism of CTB regulation of CAM expression is not fully understood. The infiltration model of CTB in vitro culture suggests that hypoxic tension can inhibit CTB in vitro infiltration by regulating CTB adhesion phenotype. Pijnenbong et al found that CTB exists in patients with pregnancy-induced hypertension. Intrinsic defects make it impossible 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 CTB autocrine and paracrine processes, such as Epidermal growth factor, insulin-like growth factor, transforming growth factor, etc. 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 vascular network in human body. The placenta is an organ filled with vascular network. VEGF plays an important role in the development of placental blood vessels.
Experiments show that VEGF plays a role in all stages of pregnancy. In early pregnancy, VEGF is associated with placental neovascularization and trophoblast differentiation and infiltration. In middle and late pregnancy, it may reduce blood flow resistance, improve local vascular permeability, and strengthen The role of substance exchange, human placenta VEGF is mainly distributed in cytotrophoblasts, syncytiotrophoblast cells, vascular endothelial cells and villous mesenchymal cells, VEGF in the placenta is mainly secreted by syncytiotrophoblasts, can affect the formation of placental vascular network and nourish cells themselves Differentiation, infiltration, Zhang Wei, Liu Xia, etc. confirmed that during pregnancy-induced hypertension, the VEGF secretion and placental vascular density of placental villus trophoblasts were significantly reduced, and 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 is specifically acting on endothelial cells, the placenta is an organ filled with vascular networks, during placental vascular development and fetal growth, VEGF plays an important role, VEGF expression is down-regulated, may cause placental blood Changes in construction, decreased placental vascular area, affecting the blood supply to the placenta, decreased VEGF levels indicate that it affects the differentiation and proliferation of trophoblasts, causing trophoblastic invasion dysfunction, thereby affecting the physiological changes of the spiral arterioles, leading to pregnancy-induced hypertension happened.
(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. PLGF-1, PLGF-2, PLGF-3 are currently found. Three isoforms, the gene located in the q24~q31 region of human chromosome 14, can specifically bind to the tyrosine kinase receptor (FLT-1) on the cell surface to play a biological role, PLGF not only has induced blood vessels Endothelial proliferation and activation, and regulation of trophoblast proliferation, in vitro culture found that trophoblast cells can express PLGF receptor, PLGF in the placenta local regulation of endothelial cells and trophoblasts through autocrine and paracrine Function, hypoxia can inhibit the secretion of PLGF in trophoblast cells. Liu Wei and other studies have shown that the expression of PLGF in peripheral blood and placenta of patients with pregnancy-induced hypertension is significantly lower than that of normal pregnant women, and the expression of PLGF decreases with the increase of pregnancy-induced hypertension. The expression of PLGF mRNA in placenta and decidual trophoblast cells was significantly decreased, indicating that the transcription of PLGF mRNA was decreased, resulting in decreased secretion of PLGF protein, which affected its biological function. The decrease of PLGF synthesis in gestational high-trophic trophoblasts occurs at the level of gene transcription. The weak synthesis ability of trophoblastic PLGF can weaken the proliferation and infiltration ability of extravillous trophoblast cells, hinder the process of vascular recasting, and cause placental ischemia and hypoxia. Lead to pregnancy-induced hypertension, hypoxia inhibits the secretion of PLGF by syncytiotrophoblasts and mesenchymal trophoblasts. After endothelial cells are damaged, the repairing ability is weakened, which promotes the development of placental ischemia and hypoxia.
With the deepening of the research on the mechanism of pregnancy-induced hypertension, it has been found that systemic vascular endothelial cells are extensively damaged, and vascular dysplasia at the placenta and decidua is a basic pathological change of pregnancy-induced hypertension, and immune-mediated trophoblastic infiltration may be a deficiency. The key factor is that due to insufficient infiltration of uterine spiral artery by trophoblast cells, it affects the recasting of physiological placental blood vessels in pregnancy, resulting in fetal placental unit ischemia, hypoxia, and the production and release of a large number of toxic factors, which cause extensive vascular endothelial cell damage. In view of the physiological and pathological effects of PLGF, it is speculated that abnormal expression of PLGF may be involved in the pathogenesis of PIH.
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 (Angiosin I, AngI). :Restriction fragment length polymorphisms (RFLP) are associated with hypertension, but family analysis by Arngrimsson et al. showed no statistical difference in RFPL between patients with pregnancy-induced hypertension and their spouses, suggesting that the renin gene There was no correlation between RFLP and the occurrence of 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 regulation of water and salt balance. Angiotensin II receptor (angiotensin receptor) , ATR) is an effector of RAS, mediates the physiological effects of angiotensin II (Ang II), is a key link in the role of RAS, plays an important role in regulating blood pressure, fluid balance and vascular recasting, while AGT is before AngII. Body, AGT molecule has two amino acid types at position 235: methionine (Met235) and threonine (Thr235), of which Thr235 type AGT is closely related to the occurrence of essential hypertension, and the AGT gene associated with pregnancy-induced hypertension is currently found. There are 4 types of mutations:
In 11993, Ward et al found that the frequency of T235 AGT gene was significantly increased in patients with pregnancy-induced hypertension, accompanied by increased levels of peripheral blood AGT. 20% of homozygous T235 women in the Caucasian population developed pregnancy-induced hypertension, and homozygous : Less than 1% of M235 women will develop pregnancy-induced hypertension, suggesting that M235 may be a protective gene for pregnancy-induced hypertension.
2Arngrimsson et al. analyzed the susceptibility of patients with PIH to AGT and found that AGT promoter A(-6)G mutation has a strong linkage disequilibrium with T235 gene. Most T235 and promoter A (- 6) G mutation linkage, only 1% to 3% of T235 is not linked to promoter A(-6)G mutation, suggesting that AGT promoter region mutation may be a deeper cause of pregnancy-induced hypertension, this mutation makes T235 expression is increased.
In 1995, Houe et al found that there were CT base mutations in the 28 nucleotides of AGR gene in patients with pregnancy-induced hypertension, which led to the change of leucinephenylalanine (LIop) in the 10th amino acid of the molecule. A position is located at the junction of renin-molecular fissures, which makes the reaction of renin-catalyzed AGT into AngII faster, leading to an increase in the normal amount of AngII, uterine spiral artery recasting disorder in patients with pregnancy-induced hypertension, and vascular smooth muscle hyperplasia and atherosclerosis. Axyl is a mitogen that stimulates proliferation of vascular smooth muscle cells. Locally elevated AngII promotes and develops atherosclerotic lesions. Morgan et al believe that only uterine spiral arteries are localized in the decidua of patients with pregnancy-induced hypertension. Smooth muscle production, T235 type AGT gene expression increased, and T235 type AGT increased, resulting in local AngII increase, accelerate the atherosclerotic pathological changes of the uterine spiral artery, LIop mutation can produce the corresponding encoded protein into the blood, indicating LIop mutation The AGT is functional, and further studies have found that LIop mutations significantly increase renin and vascular tone Catalytically converting enzyme (angiotensin converting enzyme, ACE) reaction efficiency, is directly related to the occurrence LIop pregnancy induced 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 regulation of vascular physiology. The ACE concentration is significantly correlated with its genetic polymorphism. The insertion/deletion of an ALU sequence containing the factor 16 of the gene (insertion/deletion, I/) D) Polymorphism affects the rate of transcription. When the Alu repeat (insertion type, type II) is present, the transcription rate of the ACE gene decreases, thereby reducing the synthesis, among the three genotypes of the ACE gene (II, DD, I). /D), the highest level of DD-type ACE, followed by I/D type, the lowest type II, Zhou Ning, Zhu Mingwei, Wu Yanyi, Shang Tao, etc. detected ACE genotypes in patients with pregnancy-induced hypertension and normal pregnancy The frequency and concentration of DD>I/D>II, indicating that DD or D alleles are dominant in pregnant women with pregnancy-induced hypertension, suggesting that the 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 due to the control of the gene Plasma and intracellular ACE expression, DD type plasma concentration is high, AngII production increases, while bradykinin degradation causes epoprostenol (prostacyclin) and prostaglandin E2 (PGE2) synthesis barrier, but thromboxane A2 (TXA2 The synthesis did not decrease, resulting in a decrease in the ratio of PGI2/TXA2, increased peripheral vascular resistance, abnormal blood coagulation, and decreased fetal-placental blood flow, which prompted the occurrence of pregnancy-induced hypertension. Huang Yanyi and other studies have the opposite result. The ACE gene in patients with pregnancy-induced hypertension Type II is the main type, 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 is increased during pregnancy-induced hypertension, and the mechanism may be related to the reduction of vasodilator activity and the type, affinity and affinity of peripheral blood vessel ATR. 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. The main biological effects of A-1 are mediated by AT-1. In the AT-1 gene polymorphism study, Bnnardeaux et al. used PCR to amplify all the coding regions and 3' untranslated regions of the AT-1 gene in 60 patients with family-susceptible hypertension, and combined with single-strand conformation polymorphism. At the five polymorphic loci (T637C, A1062G, A1166C, G1517T and A1878G), only the C allele frequency of the 1166 polymorphic locus in the 3 region is in the family history of hypertension. The number of patients in the A1166 polymorphic locus of AT-1 gene was significantly correlated with essential hypertension. Hu Yuhong, Shang Tao et al found that the AT-1 gene A1166 nucleoside Acidic variation is significantly associated with pregnancy-induced hypertension, and AT-1 gene A116 in patients with pregnancy-induced hypertension The polymorphic variation allele C frequency of 6 loci increased significantly, and the genotype AC and CC frequency were significantly higher than that of the normal pregnancy group, suggesting that the polymorphism of the AT-1 gene A1166 locus is related to the onset of pregnancy-induced hypertension. Polygons and normal pregnancy and fetal AT-1 3 allele polymorphisms (573CT, 1062AG, A116C) and AT-1 gene 3 dinucleotide repeats (CA) n There was no significant difference in the frequency of morphological variation. However, the frequency of A4 and 573T in the alleles of the dinucleotide repeat sequence in patients with pregnancy-induced hypertension was significantly higher than that in normal pregnancy, and there was partial linkage disequilibrium in A4 and 573T. Variations in the A4 and 573T alleles may reduce AT-1 expression, affecting placental formation, placental PGI2 secretion, and placental hemodynamics.
(5) Prostaglandins and pregnancy-induced hypertension: There are two groups of prostaglandins and obstetrics closely related, PGE2/PGF2 and PGI2/TXA2, the latter is 4-8 times stronger than the former, PGE2 and PGI2 have anti-AngII The vasoconstriction causes the blood vessels to dilate, PGF2 and TXA2 have vasoconstriction, and the two form a balance. TXA2 also activates platelets, causing platelet aggregation and thrombosis. If the two are not coordinated, pathological damage can be caused. The levels of PGE2 and PGI2 in the placenta and urine were low, while the levels of PGF2 and TXB2 (metabolism of TXA2) were significantly increased. The ratio of PGE2/PGF2 and PGI2/TXA2 was significantly lower than that of normal pregnant women.
(two) pathogenesis
1. Basic pathological changes
Systemic small arterial spasm is a basic lesion. Due to small arterial spasm, stenosis of the lumen, increased peripheral resistance, slower blood flow, vascular endothelial cell damage, increased permeability, leakage of body fluids and proteins, and insufficient microcirculation perfusion. Ischemia, hypoxia and dysfunction of various organs.
2. Major organ pathophysiological changes
(1) Brain: The weight of normal human brain only accounts for 2.2% of body weight, while cerebral blood flow accounts for 15% of cardiac output, and brain oxygen consumption accounts for 23% of total oxygen consumption. Brain tissue is caused by small arteriolar spasm. Ischemia, hypoxia, lactic acid, adenosine and other metabolites increase, vasodilation, increased permeability, cerebral edema, eclampsia patients have cerebral edema, a large number of recent CT findings found that cerebral edema is pre-eclampsia patients The main pathophysiological phenomena, hypoxia, vasospasm, exudation, edema can cause neurological disorders, headache, dizziness, nausea, vomiting, disturbance of consciousness and convulsions. In severe cases, the cerebral vascular self-regulation function is lost, causing punctiform or Localized plaque hemorrhage, brain cancer, etc., EEG can have epileptic discharge performance, cerebral blood flow map to determine the higher blood pressure of critically ill patients, the lower the amplitude of the left side can appear.
(2) Heart: Coronary artery spasm, causing myocardial insufficiency, interstitial edema, severe bleeding and necrosis, water and sodium retention in patients with pregnancy-induced hypertension, blood concentration and increased blood viscosity, causing cardiac preload and cardiac output Decreased blood volume and increased left ventricular afterload, leading to left heart failure and pulmonary edema, echocardiography showed that the right ventricular diastolic diameter of patients with pregnancy-induced hypertension was significantly enlarged, left ventricular end-diastolic pressure increased, ventricular systolic function decreased, left Ventricular ejection fraction decreased, because patients with severe pregnancy-induced hypertension have varying degrees of anemia, hypoproteinemia, decreased plasma colloid osmotic pressure, resulting in small or moderate effusions in the pericardium, and endocardial biopsy in patients with severe pregnancy-induced hypertension. Cell hypertrophy, brain-like particle changes, myocardial interstitial with limited fiber changes, and spotted hemorrhage and localized necrosis.
(3) Lung: Pulmonary edema and diffuse bronchial hemorrhage are the most common pathological changes in patients with eclampsia, and small area fibrosis is also common.
(4) Liver: Hepatic artery ischemia caused by hepatic arteriolar spasm in patients with pregnancy-induced hypertension, but the gross lesion of the liver is only seen in patients with eclampsia, about 1/3 is abnormal under the microscope, generally starting from the liver sinus Later, it can be extended to adjacent venous blood vessels. In severe cases, vascular rupture, hepatic parenchymal hemorrhage and subcapsular hematoma, upper abdominal pain and discomfort, and even hematoma rupture to abdominal cavity bleeding.
When hepatic arterioles are paralyzed, hepatocytes are ischemic, swollen, and cell membrane permeability is increased, alanine aminotransferase (ALT) release in hepatocyte mitochondria, patient ALT, aspartate aminotransferase (AST), alkali Sex phosphatase (AKP), bilirubin can be elevated, mild jaundice, lipid metabolism has also changed significantly, blood very low density lipoprotein may be one of the causes of endothelial damage, under normal circumstances, plasma albumin can In combination with non-lipidated free fatty acids, triglyceride is reduced in blood vessels, and when the ratio of plasma albumin to very low density lipoprotein is decreased, triacylglycerol can accumulate in blood vessels and damage blood vessels.
(5) Kidney: In normal pregnancy, kidney volume increases, renal plasma flow rate and glomerular filtration rate increase, metabolite excretion increases, renal arterioles sputum during pregnancy-induced hypertension, and glomerular mildness under light microscope Smaller, the diameter of the capillary lumen of the renal tubule is reduced. Under the electron microscope, the glomerular capillaries are thickened, the endothelial cells are enlarged, the capillary lumen is small or even occluded, resulting in a decrease in blood flow, and there may be a large number of glomerular lesions. Or piles of grape-like lipids, possibly cholesterol or cholesterol.
In normal pregnancy, glomerular macromolecular protein can not be filtered, small protein can be filtered, but can be reabsorbed by renal tubules. Renal blood flow is reduced in patients with pregnancy-induced hypertension, glomerular filtration rate decreases, and kidney is small. The ball can also have infarction, and there are fibroids under the endothelium, which can make the anterior small arterioles of the glomeruli extremely narrow, causing glomerular damage, increasing its permeability, decreasing selectivity, and the passage of macromolecular proteins. .
(6) Placenta: In order to ensure the blood supply to the fetus during normal pregnancy, the placental position of the blood vessels is dilated by the trophoblasts, the diameter of the uterine spiral artery is obviously increased, the endothelium is replaced by the trophoblast, the smooth layer of the middle layer of the blood vessel and the inner elastic layer are trophoblasted and Instead of the amorphous matrix containing fibers, these changes gradually extend from the aponeurotic segment of the spiral artery to the muscular layer and even to the distal end of the uterine artery. However, the placental position of the women with pregnancy-induced hypertension lacks this physiology. Altered, or limited to the vascular portion of the aponeurosis, the muscular layer of the spiral artery still retains the composition of vascular smooth muscle and decidua during non-pregnancy. Due to the damage of the placental spiral artery endothelial cells, the decrease of blood flow between the villi causes a decrease in placental perfusion. The uterus placental blood vessels have acute atherosclerosis, and the affected blood vessels can be necrotic. The blood vessel wall components are often replaced by amorphous substances and foam cells, and may progress to the disappearance of blood vessels. These lesions are most common in the basilar artery because of these arteries. No trophoblastic response occurs, and the phenomenon of vascular disappearance is consistent with the placental infarction area.
Microscopic observation: cell necrosis and degeneration in the syncytium cell layer in the placenta, decreased microvilli density of viable cells, decreased endocytic cell pinocytosis and secretion activity, increased number of cytotrophoblast cells, high mitotic activity, nourishment The base film is irregularly thickened.
Prevention
Pregnancy-induced hypertension syndrome prevention
1. Monitoring of pregnancy-induced hypertension: Since the cause of pregnancy-induced hypertension is not completely clear, the disease cannot be completely predicted. For pregnant women with high-risk factors, appropriate treatment should be given, and follow-up should be closely followed for early diagnosis, early treatment, and reduction. The occurrence of severe pregnancy-induced hypertension is of great significance to the protection of maternal and child health.
(1) Clinical observation (physical methods):
1 mean arterial blood pressure (MAP): mean arterial pressure (MAP) = diastolic blood pressure + 1/3 pulse pressure, MAP (MAP-2) level in the second trimester due to hemodilution and placental circulation, blood flow resistance Decreased, lowering blood pressure, especially diastolic blood pressure is more obvious, so that pulse pressure is increased, MAP is lowest at 22-26 weeks of gestation, and those with predisposition to pregnancy-induced hypertension have increased sensitivity to AngII, vasospasm and blood pressure. MAP-2 85mmHg, the probability of occurrence of pregnancy-induced hypertension in the future is high, but the false positive rate is also high, so it has been suggested that MAP-2 90mmHg can improve sensitivity.
2 roll over test (ROT): measurement method: generally in the 26 to 30 weeks of pregnancy, pregnant women in the left lateral position to measure blood pressure, turn over the supine 5min and then measure blood pressure, if the supine position diastolic pressure compared to the left lateral position 20mmHg is positive, suggesting that pregnant women may have the possibility of developing pregnancy-induced hypertension. In the supine position, the pregnant uterus compresses the abdominal aorta, which can increase the sensitivity of angiotensin II, increase blood pressure, and post-pregnant women with high angiotensin sensitivity. Pregnancy-induced hypertension may occur.
3 body mass index (BMI): determination method: BMI = weight / height 2 × 100, mid-pregnancy BMI 0.24, the incidence of pregnancy-induced hypertension can be as high as 20.8%, and <0.24, pregnancy-induced hypertension The incidence rate is only 4.4%, and people with short stature tend to have pregnancy-induced hypertension.
4 isometric handgrip exercise test (IET): increase systemic vascular resistance and increase blood pressure. The response to this test with diastolic blood pressure can show the reactivity of pregnant women's blood vessels, predict pregnancy-induced hypertension, determination method: pregnant women The left lateral position rested for 10 minutes, and the left arm blood pressure was measured. The pregnant woman used the left hand to compress another pre-inflated sphygmomanometer inflation belt with maximum force for 30 s. After determining the maximum pressure, the maximum pressure was held for 3 min at 50%, and then the left arm blood pressure was measured. , rising 20mmHg is positive.
(2) Laboratory inspection:
1 Fibronactin (FN): is a macromolecular glycoprotein. FN in plasma mainly comes from liver and vascular endothelial cells. It mainly exists on the basement membrane of vascular endothelium. When vascular endothelium is damaged, FN is released excessively. In the blood, studies have shown that FN can be elevated in early pregnancy, and it is significantly increased after the second trimester, and can be elevated 4 weeks before the onset of hypertension and proteinuria. Inconsistent, there are reports >255mg/L or >539mg/L for abnormalities. Cazarchick reported a positive predictive value of 94% when plasma FN400g/ml. It is suggested that the FN value in plasma be dynamically monitored, and the predicted value is higher.
2 urinary calcium determination: Some scholars found that pregnant women with pregnancy-induced hypertension glomerular filtration rate decreased in the second trimester, urinary calcium excretion was significantly lower than normal pregnant women, urinary calcium excretion was low during 10 to 24 weeks of pregnancy, and later pregnancy The probability of high levy increased, with <195mg/24h as the predictive value of pre-eclampsia, 95% confidence limit was 87%; >195mg/24h, 95% confidence was 2%, there was a significant difference.
3 urinary microalbumin/creatinine ratio (Pr/Cr): The glomerular basement membrane may pass the plasma protein with molecular weight <40,000 under normal conditions, but the renal tubules can be absorbed. When the glomerulus has mild lesions, Its permeability increases, albumin rises in the urine, and glomerular damage can be detected early by measuring different molecular weight proteins. It is reported that when the pregnancy is 20 to 30 weeks, the Pr/C ratio of fasting urine is >16. Pregnancy-induced hypertension.
2. Precautionary measures for pregnancy-induced hypertension:
(1) Establish a sound three-level maternal and child health care network, strengthen the health education for women of childbearing age, and make them understand the harm of pregnancy-induced hypertension to mothers and children, so that grassroots maternal and child health organizations can conduct prenatal examinations for them.
(2) Improve the quality of prenatal examinations, systematically manage pregnant women, and strengthen supervision of high-risk groups.
(3) Guide the food hygiene and nutrition of pregnant women during pregnancy, and eat foods with low calorie, high protein and fresh vegetables.
(4) Calcium supplementation during pregnancy survey of low-calcium diets shows that the incidence of pregnancy-induced hypertension is much higher than that of people with high-calcium diet. Calcium can reduce the sensitivity of vascular smooth muscle to angiotensin II, stabilize cell membrane, and maintain Calcium and calcium balance, Cong Kejia suggested that calcium supplementation time starts from 20 to 24 weeks of pregnancy or 28 to 32 weeks of pregnancy, and 2 g of calcium is better every day.
(5) Oral low-dose aspirin: imbalance of prostaglandin and thromboxane in pregnancy-induced hypertension, low-dose aspirin can prevent platelet aggregation, increase AngIII, prevent microthrombosis and endothelial cell damage, some scholars report 50 ~ 100mg / d Aspirin is a preventive for pregnancy-induced hypertension, but some people do not advocate the routine use of aspirin to prevent pregnancy-induced hypertension, as it may increase prenatal, postpartum and postpartum hemorrhage and neonatal natural hemorrhagic disease.
(6) Vitamin E prevents pregnancy-induced hypertension: Vitamin E is an antioxidant, and lipid peroxidation is enhanced in patients with pregnancy-induced hypertension. It has been pointed out that vitamin E is used to prevent pregnancy-induced hypertension.
Complication
Complications of pregnancy-induced hypertension syndrome Complications, cerebral hemorrhage, subarachnoid hemorrhage, coma, acute heart failure, hemiplegia, placental abruption
Symptom
Symptoms of pregnancy- induced hypertension syndrome Common symptoms Pregnancy-induced hypertension, pregnant women, calf edema, umbilical cord blood flow, high blood pressure, nausea, abdominal pain, dizziness, convulsion, edema, ascites
The clinical manifestations of pregnancy-induced hypertension are mainly three major clinical symptoms such as hypertension, proteinuria and edema.
Hypertension
Vasospasm causes blood pressure to rise. Before 20 weeks of gestation, blood pressure is generally the same as before pregnancy or slightly lower than pre-pregnancy. After 20 weeks of gestation, if blood pressure continues to rise to 140/190 mmHg or 30/15 mmHg is higher than basal blood pressure. Abnormal blood pressure, according to statistics, normal people have regular changes in blood pressure within 24 hours of 1 day, so some people advocate using mean arterial blood pressure (MAP) > (systolic blood pressure + diastolic blood pressure × 2) ÷ 3 or Diastolic blood pressure + 1/3 pulse pressure) to distinguish its severity, MAP103 ~ 114mmHg for mild pregnancy-induced hypertension, 115 ~ 126mmHg for moderate pregnancy-induced hypertension, > 127mmHg for severe pregnancy-induced hypertension.
2. Edema
The average weight gain of normal pregnant women is 0.5kg per week. The weight gain of obese pregnant women should be reduced compared with the weight loss of pregnant women. During the pregnancy, due to the swelling of the uterus, the inferior vena cava is blocked, causing fluid retention. The initial performance is that the weight gain is too fast (hidden Sexual edema), if the weight gain is 1kg within 1 week, there may be hidden edema, more than 2kg is the warning value of recessive edema, should pay close attention to other signs, if the body fluid accumulation is too much, manifested as dominant edema, may appear Clinically visible edema, edema is mostly caused by the sacral part, extending upwards, and the foot and calf have obvious depression edema. After rest for more than 6h, it does not subside. It is expressed by (+) and extended to the thigh (++) Generally, it has clinical significance); edema is extended to the abdomen and vulva (+++); systemic edema is represented by (++++), which may be accompanied by peritoneal effusion.
3. Proteinuria
Generally appear later than edema and elevated blood pressure, simple proteinuria should be considered nephropathy, proteinuria predicts increased glomerular permeability, can be measured by random clean urine or 24h urine protein, as often (+ Urine protein or urine protein > 500mg / 24h, it is a pathological phenomenon.
4. Fundus changes
Fundus changes are a serious reference indicator for the severity of pregnancy-induced hypertension, because the only system that can see the small arteries in the body is the retinal arteries. The fundus changes in pregnancy-induced hypertension syndrome can be divided into three phases: 1st Period, vasospasm: visible arterial diameter is uneven, the wall surface is enhanced, and then progresses to narrow, the arteriovenous ratio changes from normal 2:3 or 3:5 to 1:2 or 1:3; Period, vascular sclerosis: edema, exudation; stage 3, retinopathy: edema is obvious, sometimes cotton-like oozing, and even flaming hemorrhage, edema, exudation can cause retinal exfoliation, patients may have Blurred vision, and even sudden blindness, these lesions can gradually recover more than postpartum, and vision can be gradually improved.
5. Other symptoms
Patients with pregnancy-induced hypertension may have headache, dizziness, golden flowers in front of the eyes, blind spots, upper abdominal pain, nausea, vomiting, disturbance of consciousness, convulsions, severe pleural effusion, ascites, pulmonary edema, pericardial effusion, heart failure , placental abruption and so on.
Examine
Examination of pregnancy-induced hypertension syndrome
1. Blood routine: There may be anemia, blood concentration, thrombocytopenia, etc.
(1) Hb < 110 g / L, RBC < 3.5 × 10 12 / L is anemia.
(2) Hematocrit (HCT) > 35% may have blood concentration, combined with urine specific gravity > 1.02, blood rheology in whole blood viscosity > 3.6, plasma viscosity > 1.6, considered blood concentration.
(3) Platelet count: Dynamic observation of platelet count, generally <100 × 10 9 / L for thrombocytopenia.
(4) Coagulation function test: fibrinogen decreased (<1.6g / L, for clotting factor consumption); prothrombin time was longer than normal; antithrombin III (AT-III) decreased [normal value (37.74 ± 9.35) mg/dl]; fibrin degradation products (FDP) are elevated.
2. Liver function test: hepatocyte ischemia, hypoxia, so that the permeability of hepatocytes is enhanced, mitochondria release transaminase (ALT), the transaminase in the blood is light, moderately elevated, and bilirubin is mostly in the normal range. Within, there is an increase in bilirubin in the microvascular inner hemolysis, a decrease in plasma protein, and an inversion of albumin and globulin.
3. Renal function test:
(1) Blood uric acid level: The liver's function of destroying uric acid and renal excretion of uric acid is decreased, and the level of uric acid in the blood is increased. The degree of increase is positively correlated with the condition and is an extremely sensitive indicator.
(2) Urea nitrogen and creatinine: Urea nitrogen and creatinine levels increased during severe pregnancy-induced hypertension.
(3) 2-microglobulin (2-MG): 2-MG is a small molecule protein with a molecular weight of only 11800, which is present on the surface of nucleated cells and can be produced and exfoliated at any time. A part of the intact histocompatibility antigen on the cell membrane, except for mature red blood cells and placental trophoblast cells, all other cells contain 2-MG, which is mainly produced by lymphocytes. When the cells are in the most vigorous physiological state, 2-MG is produced. The fastest, the concentration of 2-MG in the human body is quite constant, easy to pass the glomerular filtration membrane, about 99.9%, absorbed by the proximal convoluted tubule, almost all decomposed and metabolized in the kidney, will not be absorbed into the blood in the original shape. For example, renal tubular damage reabsorption, 2-MG is significantly increased from the urine, with the increase of pregnancy-induced hypertension, serum 2-MG increased significantly, so the determination of serum 2-MG can be found early impaired renal function When the serum value is >2.5 mg/L, it means glomerular filtration disorder.
4. Lipid metabolism test: pregnancy-induced hypertension is often accompanied by lipid metabolism disorder, triglyceride (T) is elevated, cholesterol (C) / T ratio <1, high-density lipoprotein (HDL) is lower than normal pregnant women, and low-density lipoprotein (LDL) is elevated.
5. Electrolyte examination: patients with severe pregnancy-induced hypertension, often accompanied by electrolyte imbalance, in the presence of acidosis, hyperkalemia may occur.
6. Urine examination: Qualitative and quantitative determination of urine protein can reflect the condition, generally take a clean mid-stage urine test, pay attention to urine specific gravity, urine protein and microscopic examination, if more red blood cell casts appear on the microscopic examination, it indicates kidney function May be damaged, 24h urine protein quantification 0.5g suggest that the condition is serious, should be treated in time.
Other auxiliary inspections:
1. Electrocardiogram examination: to understand the condition of heart damage, whether there is hyperkalemia or hypokalemia, patients with severe pregnancy-induced hypertension may have myocardial ischemia.
2. Echocardiography: To understand the function of the heart, echocardiography in patients with severe pregnancy-induced hypertension can show heart enlargement, cardiac hypertrophy, pericardial effusion, and sometimes left ventricular ejection fraction.
3. CT or magnetic resonance examination: pregnant women generally do not have CT examination, it is reported that 20% of patients with preeclampsia have cerebral ischemia and edema, 50% of patients with eclampsia have cerebral ischemia, edema or cerebral infarction, generally It is believed that the amount of CT radiation has no effect on the fetus in the late pregnancy, the imaging of magnetic resonance is more clear, and the effect on the mother and the fetus is less, but the price is more expensive.
4. Fetus, placental function test: placental ischemia and hypoxia in patients with severe pregnancy-induced hypertension, resulting in intrauterine growth restriction, severe cases or even fetal death, so timely understanding of the fetus, placental function and fetal maturity, so Correct treatment can be done by measuring blood 24h urinary estriol (E3) levels, placental lactogen (HPL), pregnancy-specific -glycoprotein (SP1), fetal maturity (eg lecithin/sphingomyelin in amniotic fluid) Ratio, L/S), phosphatidylglycerol (PG), lamellar body, NST, OGT/CST, fetal biophysical score (BPS), and self-monitoring of fetal movement, fetal heart rate, understanding fetal growth and development, determination The timing of termination of pregnancy.
Diagnosis
Diagnosis and differential diagnosis of pregnancy induced hypertension
diagnosis
Diagnosis can be made based on medical history, clinical manifestations, and auxiliary examinations.
Differential diagnosis
1. Primary hypertension or chronic hypertension: more family history, mainly showing elevated blood pressure, occurring in the first 20 weeks before pregnancy, general edema and proteinuria, often no symptoms, urine routine microscopic examination generally no red blood cells and tubes Type, early pregnancy renal function test is normal, especially uric acid level is not elevated, fundus is characterized by arterial thinning, arteriovenous cross compression phenomenon, small arteriosclerotic hypertension, although postpartum blood pressure can be reduced, but can only recover Pre-pregnancy levels, and patients with pregnancy-induced hypertension have normal blood pressure before 20 weeks of gestation. After 20 weeks of gestation, blood pressure rises and often accompanied by varying degrees of edema, headache, dizziness, chest discomfort and proteinuria. In severe cases, urine may appear. The tube type and blood uric acid are elevated, and the fundus examination is small arterial spasm. In severe cases, hemorrhagic exudation or retinal detachment may occur, and these lesions gradually recover more than postpartum.
Patients with essential hypertension with pregnancy-induced hypertension must be determined according to the history and the time and extent of blood pressure rise. Patients with primary hypertension are prone to pregnancy-induced hypertension, and the time of pregnancy-induced hypertension is higher than that of pregnant women. It is early.
2. Chronic nephritis: There is already a history of acute and chronic nephritis before pregnancy, and there are different 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. And renal dysfunction, persistent blood pressure, fundus examination may have nephritic retinopathy, occult nephritis is difficult to identify, you must carefully ask the history, if necessary, further glomerular and tubular function tests, and pregnancy-induced high The patients were ill after 20 weeks of gestation, and the amount of proteinuria was variable, accompanied by varying degrees of edema. In severe cases, there may be casts in the urine and increased 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 temporary central nervous system dysfunction caused by recurrent episodes of abnormal neuronal discharge. It is a transient brain dysfunction. Therefore, it is also present before pregnancy. A similar history of seizures, in the case of a large episode, the continuous contraction of the whole body muscle, the loss of consciousness after a few seconds of convulsions, and the EEG suggesting an epileptic discharge wave. If the patient does not have a pregnancy-induced hypertension, it is generally not accompanied by an increase in blood pressure. Epilepsy and proteinuria manifestations, epilepsy can occur at any time during pregnancy, and eclampsia occurs after 20 weeks of gestation, the clinical manifestations of severe pregnancy-induced hypertension before the onset, convulsions last longer.
(2) snoring: snoring convulsions often have certain emotional stimuli, only when others are present, conscious, convulsions have no regularity, mostly no large, urinary incontinence, after the event can still recall the episode, nervous system and brain The electrogram was checked normally.
(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.
