The common term stroke refers to loss of
neurologic function caused by death of brain cells
due to hemorrhagic infarction (cerebral hemorrhage)
or ischemic infarction (cerebral thrombosis). The
term TIA (transient ischemic attacks) refers to
temporary loss of some brain functions due to
reversible ischemia, often caused by a spasm of
Causes of Brain Hypoxia and
1. Functional hypoxia due to diminished partial
pressure of oxygen (pO 2) in the inspired
2. Severe hypoxia due to generalized
cardiovascular failure, such as in cardiac arrest.
3. Impaired oxygen carrying capacity due to
4. Impaired oxygen carrying capacity due to
toxins, such as carbon monoxide.
5. Temporary perfusion deficits caused by
6. Long-lasting perfusion deficits caused by
7. Inhibition of oxygen metabolism by poisons,
such as arsenic.
(inhibition of oxygen metabolism by impaired
function of oxygen metabolism due to cumulative
burden of environmental and microbial toxins as well
as toxic organic acids produced in excess due to
acidosis and oxidosis).
Two important molecular pathways
in anoxic and dysoxygenetic brain injury are
noteworthy. In the first, initial oxygen deficiency
leads to overproduction of certain excitatory amino
acid neurotransmitters (including glutamate and
aspartate). That, in turn, seriously threatens the
neuronal metabolism by further reducing oxygen
supply. The putative mechanism of such injury
involves persistent opening of such specific
membrane channels as NMDA (N-methyl-D-aspartate
receptor) that maintains uncontrolled and dangerous
influx of calcium ions. Increased intracellular
calcium promotes cell apoptosis in addition to exert
other cytotoxic effects.
The second mechanism of
incremental neuronal injury involves activation of
nitric oxygenase, an enzyme that plays crucial
regulatory roles in health by carefully controlling
the production of nitric acid, another important
neurotransmitter and a highly potent toxin when
present in excess.
Very mild forms of ischemic
encephalopathy may cause short periods of mental
confusion with full recovery. In moderate cases,
there is progressive impairment of mentation which,
unless expeditiously reversed, leads to permanent
functional loss. In severe cases, extensive necrosis
of brain parenchyma leads to diffuse softening of
the brain parenchyma so that brain tissue becomes
diffluent and freely flows through fingers when the
brain is pulled out of the skull at autopsy.
Discrete areas of brain
necrosis (infarction) usually result from:
1. Thrombotic occlusion due to
arteriosclerosis developing within the brain.
2. Embolic occlusion due to
emboli formed outside the brain and carried in there
(as in atrial fibrillation).
3. Cerebral hemorrhage due to
leaking or rupture of blood vessels, as in malignant
hypertension (lacunar state) and aneurysm blow-outs.
5. Hemorrhage in neoplasia.
About 15% of cases of cerebral hemorrhage die
with or without treatment.