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Pathology of the nervous system
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PATHOLOGY OF THE NERVOUS SYSTEM
Explanation for working with teaching material.
1. Examine the lecture information and guide.
2. Give answers to the tests.
3. Give the answers to one of the proposed variant of the final control.
LECTURE
Anatomically and functionally the brain is the most complex structure in the body. It controls our ability to think, our consciousness of things around us, and our interactions with the outside world. Signals to and from various parts of the body are controlled by very specific areas within the brain. This renders the brain much more defenceless to focal lesions than other organs in the body.
Mechanisms of brain Injury
The causes of brain damage include hypoxia or ischemia, accumulation of excitatory neurotransmitters, increased ICP, and cerebral edema. Deprivation of oxygen (i. e. , hypoxia) or of blood flow (i. e. , ischemia) can have harmful effects on the brain structures.
Hypoxia of brainusually is seen in conditions such as reduced atmospheric pressure, carbon monoxide poisoning, severe anemia, and failure to oxygenate the blood.
Neurons are capable of anaerobic metabolism and are tolerant of pure and chronic hypoxia; it commonly produces euphoria, listlessness, drowsiness, and impaired problem solving.
Unconsciousness and convulsions may occur when hypoxia is sudden and severe.
Ischemia can be focal, as in stroke, or global. Global ischemia occurs when blood flow is inadequate to the metabolic needs of the brain.
The brain makes up only 2% of the body weight, but receives one sixth of the cardiac output and 20% of the oxygen consumption.
Focal ischemia involves a single area of the brain, as in stroke. Collateral circulation may provide low levels of blood flow during focal ischemia. The residual perfusion may provide sufficient substrates to maintain a low level of metabolic activity, preserving neuronal integrity.
Global ischemia occurs when blood flow is inadequate to provide the metabolic needs of the brain. In contrast to persons with focal ischemia, global ischemia have no collateral circulation. Unconsciousness occurs within seconds of severe global ischemia, that results from complete cessation of blood flow, as in cardiac arrest. If circulation is restored immediately, consciousness is regained quickly. However, if blood flow is not promptly restored, severe pathologic changes take place. Energy sources (i. e. , glucose and glycogen) are exhausted in 2 to 4 minutes, and cellular ATP stores are depleted in 4 to 5 minutes.
Excitatory Amino Acid Injury
Glutamate is the principal excitatory neurotransmitter in the brain, and its interaction with specific receptors is responsible for many higher-order functions, including memory, cognition, movement, and sensation. Normally, extracellular concentrations of glutamate are regulated, with excess amounts removed
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and actively transported into astrocytes and neurons.
During prolonged ischemia, these transport mechanisms become immobilized, causing extracellular glutamate to accumulate.
In the case of cell injury and death, intracellular glutamate is released from the damaged cells.
Many of the glutamate actions are coupled with receptor-operated ion channels. One type of glutamate receptor, called - the glutamate N-methyl-D-aspartate receptor (NMDA), has been implicated in causing central nervous system (CNS) injury. The uncontrolled opening of NMDA receptor-operated channels produces an increase in intracellular calcium and leads to a series of calcium-mediated processes called the calcium cascade.
Activation of the calcium cascade leads to the release of intracellular enzymes that cause protein breakdown, free radical formation, lipid peroxidation, fragmentation of DNA, and nuclear breakdown. Drugs called neuroprotectants are being developed to interfere with the glutamate-NMDA pathway and thus reduce brain cell injury.
Increased intracranial pressure
Intracranial pressure (ICP) is the pressure exerted by the brain tissue, CSF, and cerebral blood (intracranial components) against the skull.
Initially the body uses its compensatory mechanisms to attempt to maintain homeostasis and lower ICP in the following ways:
- limiting blood flow to the head
- displacing CSF into the spinal canal
- increasing absorption or decreasing production of CSF — withdrawing water from brain tissue and excreting it through the kidneys.
But if these mechanisms become overwhelmed and are no longer effective, ICP continues to rise. Cerebral blood flow diminishes and perfusion pressure falls. Ischemia leads to cellular hypoxia, which initiates vasodilation of cerebral blood vessels in an attempt to increase cerebral blood flow. This only causes the ICP to increase further. As the pressure continues to rise, compression of brain tissue and cerebral vessels further impairs cerebral blood flow.
If ICP continues to rise, the brain begins to shift under the extreme pressure and may herniate to an area of lesser pressure. When the herniating brain tissue's blood supply is compromised, cerebral ischemia and hypoxia worsen. The herniation increases pressure in the area where the pressure was lower, thus impairing its blood supply. As ICP approaches systemic blood pressure, cerebral perfusion slows even more, ceasing when ICP equals systemic blood pressure.
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