Pathophysiological mechanisms of brain death

Pathophysiological mechanisms of brain death

Severe mechanical damage to the brain most often occurs as a result of a trauma caused by a sharp acceleration with an oppositely directed vector. Such injuries most often occur in car accidents, falls from a high altitude, etc. Craniocerebral injury in these cases is due to a sharp anti-phase movement of the brain in the cranial cavity, in which direct destruction of brain areas occurs. Critical non-traumatic brain lesions occur more often as a result of hemorrhage, either to the brain substance or to the meninges. Such severe forms of hemorrhage, as parenchymal or subarachnoid, accompanied by the discharge of large amounts of blood into the cranial cavity, trigger mechanisms of brain damage similar to those of the brain injury. To fatal brain damage is also anoxia, resulting from the temporary cessation of cardiac activity.

It is shown that if the blood completely ceases to enter the cavity of the skull within 30 minutes, it causes irreversible damage to the neurons, the restoration of which becomes impossible. This situation occurs in 2 cases: with a sharp increase in intracranial pressure to the level of systolic blood pressure, with cardiac arrest and inadequate indirect cardiac massage for the specified period of time.

To fully understand the mechanism of the development of brain death as a result of secondary damage in case of transient anoxia, it is necessary to dwell in more detail on the process of formation and maintenance of intracranial pressure and mechanisms leading to fatal damage to brain tissues as a result of swelling and edema.

There are several physiological systems involved in maintaining the equilibrium of the volume of intracranial contents. At present, it is believed that the volume of the cranial cavity is a function of the following values:

Vobsch = Vkly + Vkv + Vmozga + Vodov + Vx

Where V _total - the volume of the contents of the skull at the present time; V _blood - the volume of blood in the intracerebral vessels and venous sinuses; V _lkv - the volume of the liquor; V _brain - the volume of brain tissue; V _water - the volume of free and bound water; V _x - pathological extra volume (tumor, hematoma, etc.), normally absent in the cranial cavity.

In a normal state, all these components, which form the volume of the contents of the skull, are in constant dynamic equilibrium and create an intracranial pressure of 8-10 mm Hg. Any increase in one of the parameters in the right half of the formula leads to an inevitable decrease in the others. The fastest of the normal constituents of its volume is changing V _water and V _lkv, to a lesser extent - V _blood. Let us dwell in more detail on the main mechanisms leading to an increase in these indicators.

Liquor is formed by vascular (choroid) plexus at a rate of 0.3-0.4 ml / min, completely replacing the entire volume of CSF occurs in 8 hours, that is, 3 times a day. The formation of CSF is practically independent of the magnitude of intracranial pressure and decreases with a decrease in blood flow through the vascular plexuses. At the same time, the absorption of cerebrospinal fluid is directly related to intracranial pressure: when it increases, it increases, and when it decreases, it decreases. It was found that the relationship between the system of formation / absorption of cerebrospinal fluid and intracranial pressure is nonlinear. Thus, gradually increasing changes in CSF volume and pressure may not appear clinically, and after reaching an individually defined critical value, clinical decompensation and a sharp increase in intracranial pressure occur. A mechanism for the development of a dislocation syndrome resulting from the absorption of a large volume of cerebrospinal fluid with increasing intracranial pressure is also described. While a large amount of CSF was absorbed against the background of difficulty in venous outflow, the evacuation of fluid from the cranial cavity may be slowed, which leads to the development of a dislocation. In this case, preclinical manifestations of increasing intracranial hypertension can be successfully determined with the help of Echo.

In the development of fatal brain damage, an important role is played by the violation of the blood-brain barrier and cytotoxic edema of the brain. It is established that the intercellular space in the brain tissue is extremely small, and the stress of intracellular water is maintained due to the functioning of the blood-brain barrier, the destruction of any of its components leads to the penetration of water and various plasma substances into the brain tissue, causing its edema. Compensatory mechanisms that make it possible to extract water from brain tissue are also damaged when the barrier is broken. Sharp changes in blood flow, oxygen or glucose have a damaging effect directly on both neurons and the components of the blood-brain barrier. At the same time, changes take place very quickly. The unconscious state develops only 10 seconds after the blood supply to the brain has completely ceased. Thus, any unconscious state is accompanied by damage to the blood-brain barrier, which leads to the release of water and plasma components into the extracellular space, causes vasogenic edema. In turn, the presence of these substances in the intercellular space leads to metabolic damage to neurons and the development of intracellular cytotoxic edema. In sum, these 2 components play a major role in increasing intracranial volume and lead to increased intracranial pressure.

If you summarize all of the above, then the mechanisms leading to brain death can be represented as follows.

It was found that with the cessation of cerebral blood flow and the beginning of necrotic changes in brain tissue, the rate of irreversible death of its different sites is different. Thus, the hippocampal neurons, pear-shaped neurons (Purkinje cells), neurons of the cerebellar dentate nucleus, large neurons of the new cortex and basal ganglia are most sensitive to the lack of blood supply. At the same time, cells of the spinal cord, small neurons of the cerebral cortex and the main part of the thalamus are much less sensitive to anoxia. Nevertheless, if the blood does not enter the cavity of the skull for 30 minutes at all, it leads to complete and irreversible destruction of the structural integrity of the main sections of the central nervous system.

So, brain death occurs when the arterial blood stops coming into the cavity of the skull. As soon as the supply of nutrients to the brain tissue stops, the processes of necrosis and apoptosis begin. The most rapid autolysis develops in the diencephalon and the cerebellum. As the ventilation is carried out in a patient with a ceased cerebral blood flow, the brain is gradually necrotic, there are characteristic changes that directly depend on the duration of respiratory support. Such transformations were first detected and described in patients over 12 h on AVL in an unremarkable coma. In this regard, in most English-language and Russian-language publications, this state is referred to as the "respiratory brain". According to some researchers, this term does not adequately reflect the relationship of necrotic changes with the ventilation, while the main role is assigned to the cessation of cerebral blood flow, but this term has received worldwide recognition and is widely used to determine necrotic changes in the brain of patients whose condition meets the criteria of brain death more than 12 hours.

In Russia, a large research work to identify the correlation between the degree of autolysis of the brain and the duration of ventilation in patients who meet the criteria for brain death, conducted LM. Popova. The duration of the ventilation until the development of extrasystole was 5 to 113 hours. Accordingly, the duration of stay in this state were identified 3 stages of morphological changes in the brain, which are specific for the "respiratory brain." The picture was supplemented by necrosis of the 2 upper segments of the spinal cord (obligate sign).

• In the first stage, corresponding to the duration of the supernumerary 1 to 5 h, classical morphological signs of brain necrosis are not noted. However, already at this time, characteristic lipids and blue-green fine-grained pigment are revealed in the cytoplasm. Necrotic changes are noted in the lower olives of the medulla oblongata and the dentate nuclei of the cerebellum. Disorders of blood circulation develop in the pituitary gland and its funnel.
• In the II stage (12-23 hours of the supramarginal coma), signs of necrosis are revealed in all sections of the head and I-II segments of the spinal cord, but without pronounced decay and only with initial signs of reactive changes in the spinal cord. The brain becomes more flabby, there are initial signs of disintegration of the periventricular divisions and the hypothalamic region. After isolation, the brain spreads out on the table, the pattern of the structure of the brain hemispheres is preserved, while the ischemic change of neurons is combined with fatty degeneration, granular decay, karyocytolysis. In the pituitary gland and its funnel, circulatory disorders increase with small foci of necrosis in the adenohypophysis.
• For Stage III (supramarginal coma 24-112 h), there is a growing widespread autolysis of necrotic substance of the brain and marked signs of demarcation of necrosis in the spinal cord and pituitary gland. The brain is flabby, it does not hold the form well. Restricted areas - the hypothalamic region, hooks of the hippocampal gyri, the amygdala of the cerebellum and periventricular regions, as well as the brain stem - in the stage of decay. Most neurons in the brainstem are absent. In place of the lower olives are located multiple hemorrhages from necrotic vessels, repeating their forms. Arteries and veins of the brain surface are expanded and filled with hemolyzed red blood cells, which indicates the cessation of blood flow in them. In the generalized version, five pathoanatomical signs of brain death can be distinguished:
  • necrosis of all parts of the brain with the death of all elements of the brain substance:
  • necrosis of I and II cervical segments of the spinal cord;
  • the presence of a demarcation zone in the anterior pituitary and at the level of III and IV cervical segments of the spinal cord;
  • stoppage of blood flow in all vessels of the brain;
  • signs of edema and increased intracranial pressure.

Very characteristic of the subarachnoid and subdural spaces of the spinal cord are microparticles of the necrotic tissue of the cerebellum, carried with the flow of cerebrospinal fluid to the distal segments.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]