The Blood Brain Barrier (BBB):
The cerebral capillary is the site of the BBB. Interendothelial tight junctions impede the passage of electron-dense markers. Cerebral capillaries lack fenestrations and have tight junctions. They are active in the process of pinocytosis. All these features regulate the passage of highly polar hydrophilic molecules allowing virtually unrestricted passage of lipid-soluble substances. Cerebral capillaries have 2-4X the number of mitochondria as other capillaries. Cerebral capillaries have an array of important enzymes: ATPase, dehydrogenase, monamine oxidase, DOPA decarboxylase, acid and alkaline phosphatase, NAD and others. BBB has both central (cholinergic and aminergic) and peripheral (sympathetic and parasympathetic) innervation.
Areas without a BBB include:
Carrier Mediated BBB Movement:
Glucose and aa's are actively transported as they are not lipid soluble. These substances demonstrate stereospecifity, competitive inhibition and saturation. May be bi- or unidirectional transport. All aa's appear to use the same active transport system (flooded in PKU, aminoaciduria's etc)
Evaluation of BBB function:
Using radio-isotopes or various exclusion dyes can calculate from single pass what Km and Vmax are.In humans BBB integrity determined by:
1. external detection of radionuclide activity with a sodium iodide crystal
2. CT scanning
3. PET scan with rubidium-82
CEREBRAL EDEMA or BRAIN EDEMA:
Excess accumulation of water in the intra- and/or extracellular spaces of the brain.
Vasogenic edema: The disruption of the cerebral capillary provides the underlying mechanism for vasogenic edema. The amount of edema is greatest in the white matter (increased water and sodium in the extracellular spaces, decreased potassium); but the same changes may take place in grey matter but less so. The astrocytes become swollen. This type of edema is seen in response to trauma, tumors, focal inflammation, and late stages of cerebral ischemia.
Cytotoxic edema:This is due to the derangement in cellular metabolism resulting in inadequate functioning of the sodium and potassium pump in the glial cell membrane. As a result there is cellular retention of sodium and water. There are swollen astrocytes in grey and white matter. Cytoxotic edema is seen with various intoxications (dinitrophenol, triethyltin, hexachlorophene, isoniazid) and in Reye's syndrome, severe hypothermia, and early ischemia.
Osmotic edema:Normally CSF and ECF osmolality in the brain is slightly greater than that of plasma. When plasma is diluted by SIADH, water intoxication, hemodialysis, there is passage of water down abnormal gradient creating cerebral edema.
Hydrostatic:This form of cerebral edema is seen in acute, malignant hypertension. It is thought to result from direct transmission of pressure to cerebral capillary with transudation of fluid into the ECF.
Pathophysiology of Cerebral Edema:
This is a cascade of events involving loss of the integrity of the BBB, setting up of a vascular hydrostatic gradient, increased tissue pressure, decreased cerebral blood flow, with resulting tissue acidosis. Chemical changes include glutamate, serotonin, components of kallikrein-kininogen-inin, fatty acids
Surgical removal of offending lesion
Control of arterial blood pressure
Corticosteroids - stabilize membranes
Osmotherapy - mannitol (1 g/kg); lasix 0.7 mg per kg; glycerol 1 g/kg
Control of ICP - carbonic anhydrase, DMSO
Harrigan MR, Cerebral salt wasting syndrome. Neurosurgery 38: 152-160, 1996
Cerebral EdmeaCerebral edema is swelling of the brain which can occur as the result of a head injury, cardiac arrest or from the lack of proper altitude acclimatization.
Edema also occurs when the chemical balance of brain tissue is disturbed and water or fluids flow into the brain cells, making them swell and burst, releasing their toxic contents into the surrounding tissues. Edema is one cause of general brain tissue swelling and contributes to the secondary injury associated with stroke.
Symptoms of cerebral edema include headaches, decreased level of consciousness, hallucinations, psychotic behavior, memory loss and coma. If left untreated, it can lead to death (r. Bruce Lee).