Obstetrics and Gynecology - A.M. Hromova 2000

Early pregnancy toxicoses. Late gestosis
Late gestosis
Pathogenesis

According to the majority of contemporary researchers, immune factors play a significant role in the Pathogenesis of Late gestosis (Preeclampsia). Throughout Pregnancy, the maternal Organism produces Antibodies against fetal Antigens, which are formed As a result of the fetus inheriting paternal Genetic information. In late gestosis, the Excessive production of maternal antibodies leads to the Circulation of high concentrations of immune complexes in the Blood. By damaging the vascular endothelium at the site of their formation (primarily in the Placenta), these immune complexes cause an imbalance in the synthesis of BIOLOGICALLY ACTIVE SUBSTANCES. Specifically, there is an increase in the number of vasoconstrictive cytokines accompanied by a decrease in the synthesis of vasodilators. Among these, the endothelium-derived contracting factor and thromboxane are of paramount importance; a simultaneous surge in their concentrations triggers vasospasm, activates platelet aggregation (subsequently impairing blood rheology and leading to massive intravascular microthrombosis), and increases capillary permeability to the liquid fraction of blood, resulting in a reduced circulating plasma volume. Under conditions of hypovolemia, venous return to The Heart diminishes. This factor, combined with increased afterload (due to peripheral vasospasm) and ion-metabolic shifts, suppresses myocardial contractility and decreases Cardiac Output. The arterial bed becomes insufficiently filled, which provokes a compensatory increase in total peripheral vascular resistance (TPVR), resulting in persistent arterial Hypertension and restricted Tissue and organ blood flow. The Kidneys play a particularly crucial role in The Development of late gestosis. Restricted renal blood flow leads to a drop in the Glomerular Filtration rate, thereby decreasing the volume of ultrafiltrate entering the renal tubular system. Concurrently, the function of the tubules themselves, especially the proximal ones, undergoes significant alteration. In the proximal nephron, reabsorption is regulated by the blood levels of atrial natriuretic peptide (ANP), which is produced by the cardiomyocytes of the right atrium in response to volume overload. Amid myocardial hypodynamia and hypovolemic shifts, the heart Muscle fails to produce adequate amounts of this peptide, diminishing its effect on the renal tubular system. Consequently, the intensity of proximal sodium and Water reabsorption increases markedly, which, combined with reduced glomerular filtration, leads to a noticeable decrease in diuresis and fluid retention in the body. Although this renal response is essentially compensatory and aims to counteract hypovolemia, in late gestosis—due to progressively increasing hydrostatic intravascular pressure (driven by worsening vasospasm), declining plasma colloid-osmotic pressure (stemming from progressive hypoproteinemia caused by urinary protein loss and suppressed hepatic Protein Synthesis), and increased vascular permeability (aggravated by developing metabolic acidosis)—the fluid retained by the kidneys cannot be held within the vascular bed for long and leaks into the interstitial space, worsening edema and hypovolemia. This precipitates even more severe vasospasm, slowed blood flow, and hypoperfusion of all vital Organs, which, against the backdrop of chronic disseminated intravascular coagulation, culminates in multiple organ dysfunction syndrome (MODS). Liver dysfunction, resulting from impaired perfusion and mesenchymal edema, leads to hypo- and dysproteinemia (decreased albumin levels with a relative increase in globulins), worsening metabolic acidosis, and depressed detoxification activity, followed by the accumulation of toxic substances in the body. In the Lungs, the aforementioned hemodynamic and volemic disturbances provoke interstitial and, subsequently, intra-alveolar edema, manifesting as acute lung injury syndrome. Central Nervous system disorders are driven by two groups of factors. First, generalized vasospasm, characteristic of cerebral Arteries as well, leads to The formation of ischemic zones in Brain tissue. Second, due to renal and hepatic failure alongside metabolic acidosis, high concentrations of neurotrophic toxins accumulate in the body (products of incomplete lipid oxidation, ammonia, toxic phenols). As a consequence, the normal balance between the Cerebral Cortex AND subcortical structures is disrupted, leading to hyperactivity of the vascular, respiratory, motor, and other regulatory centers. This triggers neurological symptoms (headaches, nausea, visual scotomas, which are hallmark signs of hypertensive encephalopathy), convulsive syndrome, and, in critical cases, results in intracerebral Hemorrhage. Cerebral Hypoxia during a seizure may further induce brain edema. Due to these cerebral impairments, the Hypothalamus decreases its synthesis of releasing Hormones, and the Pituitary Gland correspondingly reduces tropic hormones, which logically leads to decreased activity of peripheral Endocrine glands—themselves functioning under hypoxic conditions. The depression of the thyroid, parathyroid, Pancreas, Adrenal Glands, and Ovaries further intensifies Metabolic Disorders throughout the body. As late gestosis progresses and uteroplacental blood flow is restricted, placental perfusion declines, impairing gas exchange and resulting in diffusion-perfusion insufficiency, commonly referred to as the "Shock placenta" syndrome. Other Functions of the placental tissue are also suppressed, most notably its endocrine function, which is accompanied by decreased blood concentrations of both placental (placental lactogen, progesterone) and fetal (estradiol, estriol) hormones, thereby compromising hormonal Homeostasis. As a result of these placental impairments and alterations in uteroplacental circulation, a mismatch arises between the fetus's needs for nutrients and oxygen and the placenta's capacity to deliver them. A further deepening of metabolic disorders in the maternal organism leads to an even greater disruption of the diffusion-trophic function of the placenta, ultimately causing intrauterine hypoxia, fetal growth restriction, and increased perinatal morbidity and mortality.