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Pathogenesis of clinical manifestations
Pheochromocytoma usually makes its debut with symptoms associated with excessive production of catecholamines and their systemic effect on organs and systems with a predominance of, as a rule, cardiovascular changes. By no means always hemodynamic fluctuations in pheochromocytoma are a direct consequence of the increased production of catecholamines directly by the tumor. One of the non-specific factors is the presence of a significant depot of catecholamines at the ends of the sympathetic nerves. Norepinephrine secreted by these endings acts on the receptors of efferent cells in the synapse. Any stimulation of the sympathetic system can stimulate a crisis caused by the neurogenic effects of norepinephrine ejected from the synaptic depot, and not their chromaffin tumor.
The most frequent and main clinical manifestation of pheochromocytoma is a hemodynamic crisis, which is characterized by a sudden increase in systolic blood pressure to 200-250 mm. RT. Art., accompanied by the appearance of unaccountable fear, a feeling of internal trembling. Pallor of the skin, or, conversely, redness of the face, is noted.
A characteristic symptom of disturbances in peripheral microcirculation during an attack is the appearance of a "marble" skin pattern, more pronounced with frequent hypertensive crises. Paroxysm of hypertension was almost always accompanied by profuse sweating. Hemodynamic crisis may be accompanied by nausea, vomiting, sharp abdominal pain.
In some patients, the main symptom of hypertensive crisis is pain in the heart. One of the most constant manifestations is a heartbeat of up to 140-180 beats per minute, much less often - normosystole or bradycardia. In some patients, paroxysm of arterial hypertension is accompanied by rhythm disturbance (the occurrence of frequent atrial and / or ventricular extrasystoles, paroxysm of sinus tachycardia, paroxysm of atrial fibrillation).
A characteristic manifestation of the hypertensive crisis in pheochromocytoma is its short duration and the so-called “self-absorption”. In the post-attack period, most patients have a normalization of the color of the skin, the disappearance or reduction of sweating, pain, sensations of internal trembling, fear. Some patients have an imperative urge to urinate, profuse urination (urine, as a rule, is light).
One of the leading syndromes in pheochromocytoma is a decrease in the volume of circulating fluid. As a result of increased peripheral vascular resistance and the effect of precapillary bypass surgery, centralization of blood circulation occurs. A significant component in the formation of hypovolemia is the exit of fluid from the vascular bed into the "third space". This is due to a change in the permeability of the vascular wall due to the formation of fibromuscular dysplasia with prolonged vascular spasm.
Important points that affect the occurrence of hypovolemia are increased sweating and chronic constipation. Hypovolemia, having a "masking" effect on the results of measuring peripheral blood pressure, often leads to diagnostic errors and incorrect medical decisions. Hypovolemia syndrome is largely responsible for microcirculatory disorders in vital organs.
In the pathogenesis of changes from the cardiovascular system, an important role is played by toxic catecholamine myocardial dystrophy. One of the most common misconceptions that leads to the late detection of pheochromocytoma is the overdiagnosis of myocardial ischemia.
It should be noted that both electrocardiographic and laboratory signs of destruction of myocardiocytes are not specific.
Based on these signs, it is impossible to draw a conclusion about the cause of myocardial dystrophy, whether it is associated with impaired patency of the coronary vessels or the direct toxic effect on myocardiocytes is important. The main reason for cardiotoxic changes in hypercatecholaminemia is intracellular disruption of the action of enzymes responsible for the phosphorylation process. High afterload on the background of non-coronarogenic myocardial dystrophy or myocardial necrosis can lead to acute left ventricular failure (cardiac asthma, pulmonary edema). With a long history of pheochromocytoma and progressive cardiosclerosis against the background of myocardial hypertrophy, concentric and then dilated cardiomyopathy occurs, which inevitably leads to chronic heart failure. Paroxysms of heart rhythm disturbance in these patients are a high risk factor for sudden cardiac death.
Against the background of an increase in episodes of catecholamine release into the bloodstream and an increase in secretion intensity, a state of “uncontrolled hemodynamics” can occur, in which there is a frequent and random change in episodes of high and low blood pressure, which is practically not corrected medically or there is a paradoxical response to drug administration. The main sign of the state of "uncontrolled hemodynamics" is considered a tendency to progressive hypotension. The main threat in the state of "uncontrolled hemodynamics" is the development of catecholamine shock.
Of the pathophysiological effects of clinical importance for pheochromocytoma, attention should be paid to the occurrence of “secondary” diabetes or impaired glucose tolerance, which is due to accelerated glycogenolysis in the liver, and a decrease in insulin production due to stimulation of pancreatic β-adrenoreceptors.
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Pathogenesis of clinical manifestations
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