I. Etiology of cerebrovascular disease.
The etiology of cerebrovascular disease refers to the causes that directly affect cerebral blood circulation leading to impaired blood supply to brain tissue and impaired brain function. There are many causes of cerebrovascular disease, broadly speaking, the following aspects.
1, vascular wall lesions: this is the most common cause. The most common is atherosclerosis, including atherosclerosis and hypertensive atherosclerosis. There are also arteritis (rheumatism, tuberculosis, connective tissue disease, parasitic infection and syphilis), developmental abnormalities (aneurysm, vascular malformation), vascular injury (cranial trauma, surgery, insertion of catheters, intracranial puncture, etc.), tumors, etc.
2, cardiac and hemodynamic changes: such as hypertension, hypotension, cardiac dysfunction caused by cardiac disorders (heart failure, atrial fibrillation, conduction block), etc.
3, blood rheology abnormalities: (1) increased blood viscosity
(1) Increased blood viscosity: hyperglycemia, hyperlipidemia, hyperproteinemia and abnormal increase in blood components (erythrocytosis, leukemia, thrombocytosis), concentration of blood components such as dehydration, etc. can lead to increased blood viscosity.
(2) Abnormalities in coagulation mechanisms: thrombocytopenic purpura, hemophilia, disseminated intravascular coagulation, and the use of anticoagulants.
(3) Others: malignant tumors, pregnancy, postpartum, postoperative and long-term application of contraceptive pills can all cause a hypercoagulable state of the blood.
4.Other.
(1) The influence of extravascular factors: cervical spondylosis, tumor compression of blood vessels resulting in insufficient cerebral blood supply.
(2) Various emboli formed outside the cranium enter the cerebral vessels with the blood flow and block the cerebral blood supply.
Second, the pathogenesis of cerebrovascular disease.
Cerebrovascular disease is disabling in mild cases and life-threatening in severe cases, which is inseparable from the physiological function of the brain, the blood circulation of the brain, and the characteristics of brain metabolism. Brain neuron metabolism demand for oxygen and glucose is much higher than other tissues, and energy consumption is also high, but energy storage is extremely limited, and must rely on uninterrupted blood circulation for timely supply, once the blood supply is insufficient or the supply stops for more than a certain period of time, the brain neuron will have abnormal function or even die. The ultimate cause of cerebrovascular disease is a sudden oversupply of oxygen and glucose between the metabolic needs of neurons and the local circulation. Disturbances in local circulation are the result of alterations in the vascular, hemodynamic and rheological factors described above. The pathogenesis of cerebrovascular disease is complex, and the pathogenesis of different types of cerebrovascular disease varies. The following is a brief introduction according to the nature of cerebrovascular disease.
1, transient ischemic attack (TIA): transient ischemic attack can be divided into two types: TIA of the carotid system and TIA of the vertebrobasilar system, both of which have different sites of ischemia, but similar pathogenesis.
(1) Blockage of blood vessels by tiny emboli: such small emboli mainly come from the atherosclerotic plaque at the beginning of the internal carotid artery and its debris shed when ulceration occurs. Because the emboli are extremely small and easily ruptured, or because the emboli move more distally due to vasodilatation at the distal end of the embolism, blood flow is quickly restored and symptoms disappear.
(2) Hemodynamic changes: The patient’s original artery is severely stenosed or occluded, and normally the blood supply can still be maintained by collateral circulation. Once blood pressure decreases, cerebral blood flow decreases and ischemic symptoms occur due to inadequate blood supply from the collateral circulation, blood pressure is quickly restored and symptoms disappear.
(3) Cervical artery compression: Mostly occurs on the basis of vertebrobasilar artery sclerosis, due to arteriosclerosis or cervical spine osteophytes compressing the vertebral artery, symptoms appear when the head and neck are tilted back excessively or suddenly turned to one side, and are relieved with the relief of arterial compression.
(4) Blood-stealing syndrome and cerebral vasospasm can also cause transient cerebral ischemic attack.
(2) Cerebral thrombosis: the most common cause is cerebral atherosclerosis, followed by inflammation of cerebral arteries. Since atherosclerosis mostly occurs at the bifurcation and bend of large blood vessels, the preferred sites of cerebral thrombosis are the middle cerebral artery, the beginning of the internal carotid artery, the vertebral artery and the middle and lower part of the vertebrobasilar artery. After the inflammation of intima or atherosclerosis forms ulcers, the inner wall of blood vessels is not smooth, and the anti-coagulant ability of normal endothelial cells is lost, so platelets, fibrin and other blood-forming components adhere to the wall of blood vessels, forming thrombus. In addition, blood pressure drops, blood flow is slow, and blood viscosity increases after excessive dehydration can promote thrombus formation.
3.Brain watershed infarction: It is a special type of brain infarction. The mechanism of cerebral watershed infarction is different from the above-mentioned types of infarction, and refers to the local ischemia in the area between the adjacent larger vascular blood supply areas in the brain, that is, the limbic zone. It is not the ischemia of one major vascular innervation zone, but the ischemia of the junction zone of several larger vascular blood supply zones (which is imaginatively called the “trivial” zone). Because this zone is the farthest from the heart, it is easily affected by the blood pressure and effective circulating blood volume of the body, especially in middle-aged and elderly people with atherosclerosis, once the systemic hypotension or reduced cardiac output of various causes occurs, infarction occurs in this zone. If the cause can be corrected in time and blood volume and blood pressure are restored, the prognosis is generally better.
4, cerebral embolism: the pathogenesis of cerebral embolism is relatively simple, mainly because emboli from different sources suddenly block the cerebral vessels, but the consequences are often serious. The source of embolus can be divided into three categories: cardiac, non-cardiac and unknown source. Cardiac cerebral embolism is the most common: wind heart disease combined with atrial fibrillation, myocardial infarction, etc. are prone to wall thrombus, and when the blood flow is irregular, it is easy to dislodge the embolus and cause cerebral embolism; subacute bacterial endocarditis inflammatory redundancy on the valve dislodged to cause cerebral embolism; rare causes include cardiac mucinous tumor, mitral valve prolapse, etc. In addition, wind heart disease and ventricular septal defect can press emboli from veins into the left heart to produce paradoxical cerebral embolism. Non-cardiogenic cerebral embolism includes: aortic arch and its emitted large-vessel atherosclerotic plaque dislodgement; infectious pus embolism caused by sepsis, fat embolism of long bone fracture, cancer cell embolism, postpartum amniotic fluid embolism, air embolism of various causes, etc. The sudden blockage of arteries by emboli causes acute ischemia in the blood supply area on the one hand, and reflexively causes cerebral vasospasm to expand the scope of ischemia on the other. Young patients are more prone to vasospasm, sometimes a small embolus can cause severe spasm and a larger infarction.
5, cerebral hemorrhage: cerebral hemorrhage and hypertension are closely related, on the basis of vascular lesions, rapid fluctuations in blood pressure can lead to cerebral vascular rupture. It is generally believed that long-term hypertension causes cerebral blood vessels to form corn-like microaneurysms below 250 μm. Because of the weakness of cerebral blood vessels themselves, coupled with cerebral arteriosclerosis caused by hypertension, the elasticity of blood vessel walls decreases, and when blood pressure rises suddenly, the microaneurysms are prone to rupture and bleeding. Therefore, cerebral hemorrhage mostly occurs during emotional excitement or strenuous exercise. In addition, malignant tumor destroying cerebral blood vessels and coagulation mechanism disorder can also cause cerebral hemorrhage.
6.Subarachnoid hemorrhage: The human brain and spinal cord are covered by three layers of membranes. The outer layer is the dura mater, the middle layer is the arachnoid membrane, and the inner layer is the soft membrane. The soft membrane adheres closely to the surface of the brain, and the cavity between the soft membrane and the arachnoid membrane is the subarachnoid space. Under normal conditions, this cavity is filled with colorless and clear cerebrospinal fluid. When the blood vessels in the soft membrane rupture, blood flows into the subarachnoid space, causing the cerebrospinal fluid to stain red, which is called a subarachnoid hemorrhage. The causes of subarachnoid hemorrhage are mostly arteriovenous malformations before the age of 30, often congenital aneurysm rupture around the age of 40, and hypertension and cerebral atherosclerotic spindle aneurysm rupture after the age of 50. Aneurysms and vascular malformations are congenital lesions, but they develop only after young adulthood, so infants and children usually do not develop them. Subarachnoid hemorrhage is most often induced by high levels of mental stress, emotional stress, and overexertion. Although the hemorrhage is not in the brain parenchyma, the consequences are very serious. On the one hand, a large amount of blood enters the ventricles and affects the cerebrospinal fluid circulation, producing severe hydrocephalus and high cranial pressure in the patient; on the other hand, the blood directly stimulates the blood vessels as well as the destruction of blood cells to produce a variety of vasoconstrictive substances, stimulating the vessels to produce extensive spasm. Subarachnoid hemorrhage is prone to recurrence and is generally considered to be most likely to recur within four weeks; the mortality rate is high, with a mortality rate of about 30% for initial hemorrhage, 60% to 70% for rebleeding, and more than 95% for recurrence. According to the regular treatment can reduce the mortality rate, and may eradicate the cause of the disease, survivors can fully recover.
7, hypertensive encephalopathy: also belongs to the category of cerebrovascular disease. Hypertensive encephalopathy is an acute brain dysfunction caused by a sudden increase in blood pressure. Its onset depends on the degree and speed of blood pressure elevation. In people with normal blood pressure in the past, a sudden rise in blood pressure to 24/16kPa (180/120mmHg) can cause the onset of the disease; in patients with chronic hypertension, the onset of the disease may occur only when the blood pressure is above 30.6-33.3/16.0-20.0kPa (230-250/120-150mmHg). There are several theories for its pathogenesis, as follows.
(1) Auto-regulatory collapse theory: Under normal conditions, equilibrium cerebral blood flow can be maintained by auto-regulation of small arteries when blood pressure fluctuates. However, this effect is limited to a certain blood pressure range. If the mean arterial pressure increases rapidly to 21.3 kPa or more, the autoregulation mechanism can be destroyed, causing vasoconstriction to become passive dilation, cerebral blood flow to increase, resulting in overperfusion, extravasation of intravascular fluid, rapid cerebral edema, increased intracranial pressure, capillary wall degeneration and necrosis, and punctate hemorrhage and microinfarction.
(2) The theory of excessive autoregulation: rapid increase in blood pressure, excessive constriction of small vessels, reduced blood flow, ischemic degeneration of the vessel wall, increased permeability, extravasation of intravascular fluid causing edema, punctate hemorrhage and microinfarction.
(3) It is also believed that hypertensive encephalopathy is caused by acute excessive elevation of blood pressure forcing excessive vasodilation and destruction of the blood-brain barrier through excessive stretching of the small arterial walls, secondary to vasogenic brain edema. For hypertensive encephalopathy, the prognosis is good if it is treated promptly and urgently; otherwise, death can occur due to brain herniation, intracranial hemorrhage or persistent convulsions.
Third, the mechanism of brain function impairment caused by cerebrovascular disease;
After the occurrence of cerebrovascular disease, how is the brain function damaged? At present, it is believed that there are mainly the following aspects.
1, energy failure: cerebral thrombosis or cerebral embolism blocked the blood supply of the distal vessels of the lesion, the neurons in the area innervated by the lesion vessels are depleted due to the reduced blood supply, insufficient supply of nutrients and energy, and the very limited energy stored in the neurons themselves is quickly depleted, and the neurons cannot complete their normal physiological functions, and acute degenerative necrosis occurs. In cerebral hemorrhage, the blood flow to the distal end of the ruptured vessel is reduced or completely stopped, resulting in the lack of energy in the brain tissue in the area innervated by the vessel.
2, secondary damage after ischemia: ischemic neurons cannot maintain normal metabolic functions, excitatory amino acids with neurotoxicity are released to extracellular in large quantities, calcium ions flow in large quantities, and oxygen free radicals are generated, which further damage brain cells, aggravate the necrosis of neurons in the ischemic area and induce apoptosis of neurons in the ischemic peripheral area.
3. Cerebral edema: cerebral edema refers to excessive water content in brain tissue. According to different causes, cerebral edema can be divided into three types. The first type is cytotoxic cerebral edema, which is due to the impaired energy metabolism of brain cells (including neurons and glial cells) after ischemia, which cannot maintain the ion balance inside and outside the cells, and a large amount of sodium ions and water from outside the cells enter the cells, and brain cells swell and produce cerebral edema. The second type is vascular-derived cerebral edema, which is caused by cerebral ischemia, insufficient energy supply of cerebral vessels themselves, swelling and damage of vascular endothelial cells, increased vascular permeability, destruction of the blood-brain barrier, and infiltration of plasma components into brain tissue and resulting in cerebral edema. The third type is interstitial cerebral edema, which is caused by subarachnoid hemorrhage, cerebral hemorrhage, and massive cerebral infarction, resulting in cerebrospinal fluid pressure elevation and cerebrospinal fluid infiltration into the interstitial brain tissue. Cerebral edema affects the exchange of substances and energy between brain cells and the outside world on the one hand, and compresses blood vessels leading to further reduction of blood flow on the other. More seriously, localized cerebral edema can displace brain tissue (medically known as brain herniation) and endanger life. This is the reason why acute cerebrovascular disease requires dehydration treatment.
4. Occupancy effect: The hematoma formed by cerebral hemorrhage and severe local cerebral edema compress the brain tissue around the lesion and produce an occupancy effect. The sudden occupancy effect can reduce the blood supply of the surrounding brain tissue, compress or even break the nerve fibers, and destroy the normal nerve conduction function. Another serious consequence of the occupancy effect is brain herniation, which threatens the life of the patient. Occupancy effects occurring in the cerebellum tend to compress the vital centers in the brainstem. Therefore, even a minor cerebellar hemorrhage can lead to “lightning” death of the patient.
5. Cerebral vasospasm: Most often occurs in subarachnoid hemorrhage. As the entire brain tissue is immersed in the bloody cerebrospinal fluid, the red blood cells and the large amount of vasoconstrictive substances produced after decomposition stimulate the blood vessels on the surface of the brain, causing extensive and continuous cerebral vasospasm and extensive ischemia of the brain tissue, which can lead to cerebral infarction in severe cases. Therefore, subarachnoid hemorrhage generally requires antivascular spasm treatment. In addition, cerebral embolism can also cause reflex spasm of the adjacent cerebral vessels and aggravate ischemic damage. Younger patients have higher vascular reactivity and cerebral vasospasm tends to be more severe.