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CNS ischemia path
CBN
35
Medical
Graduate
12/20/2010

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Term
how much of total cardiac output does the brain require? what % of total body O2 does the brain consume?
Definition
the brain requires 15% of cardiac output and uses 20% of total body O2 - therefore it is very sensitive to alterations in blood flow, O2 content or inhibition of O2 use by tissue.
Term
what are the general causes of decreased O2 delivery to the brain?
Definition
functional hypoxia (low O2 partial pressure - altitude etc), impaired O2 carrying capacity in the blood (carbon monoxide etc), inhibition of O2 use by the tissue (cyanide), and ischemia due to decreased perfusion/obstruction of large/small blood vessels.
Term
what determines the consequences of reduced blood flow to the brain?
Definition
1) the amount of collateral circulation. 2) the duration of ischemia. 3) the magnitude/rapidity of blood flow reduction. these factors will determine the *anatomic site of the lesion, the *size of the lesion, and *clinical deficit.
Term
what are the 2 types of acute ischemia?
Definition
*global cerebral ischemia: results from a general/widespread decrease in cerebral perfusion such as cardiac arrest, shock, marked hypotension (shock), and asphyxia. *focal cerebral ischemia: cessation of blood flow to localized areas of the brain due to large or small blood vessel disease.
Term
which CNS cells are most sensitive to ischemia?
Definition
neurons, however oligodendroglia and astrocytes are also sensitive.
Term
what generally characterizes minor global ischemia?
Definition
minor global ischemia may result in transient confusion w/no morphologic or functional derangements - but at times can cause permanent damage.
Term
what generally characterizes severe global ischemia?
Definition
severe global ischemia can result in a variety of clinical and morphological changes, many of them catastrophic - such as a persistent vegetative state/coma or other permanent deficits. pts affected by this may meet the definition of brain death, which is evidence of diffuse cortical injury such as a flat EEG w/brainstem damage, absent respiratory drive, absent reflexes, and absent cerebral perfusion.
Term
what is "respirator brain"?
Definition
a post mortem phenomenon where someone has been on a respirator due to their inability to perfuse their own brain characterized by: marked necrosis, edema, and widespread destruction of the brain (due to recurrent cycles of *edema+vasocompression resulting in autolysis and softening of the brain = cannot be fixed in formalin).
Term
what is the morphology of brain affected by global cerebral ischemia?
Definition
swollen brain (very problematic due to limited expansion availability), widened gyri, narrowed sulci, possible herniation (herniation through the foramen magnum: cerebellar tonsillar herniation), and ischemia/hemorrhage associated w/herniation (may lead to necrosis).
Term
what are the microscopic features of early stage (12-24 hrs) global ischemic injury in the brain?
Definition
*red neurons: neuronal cells undergo vacuolization (hole formation), become eosinophilic, pyknotic (shrinking of nuclei), and karyorrhectic (breaking up of nuclei). the *pyramidal cells of the hippocampus and *purkinje cells of the cerebellum are particularly susceptible to global ischemia which increases potentially damaging neutrophilic infiltration.
Term
what are the microscopic features of subacute stage (24 hrs - 2 wks) global ischemic injury in the brain? what characterizes repair of this type of injury?
Definition
necrosis, macrophage infiltration, vascular proliferation, and reactive gliosis (closest thing in the brain to scarring - glial cells are permanent, meaning they have permanently exited the cell cycle and no degree of stimulation will encourage them to re-enter the cell cycle). repair of this occurs around 2 wks and consists of necrotic tissue removal, loss of organized cellular structure, gliosis, and pseudolaminar necrosis (uneven destruction of the neocortex w/preservation of some areas and destruction of others).
Term
what kind of necrosis usually occurs w/cerebral infarction?
Definition
liquefactive necrosis
Term
what characterizes the etiology of focal cerebral ischemia?
Definition
usually there is a vascular component, often an arterial occlusion caused by thrombotic occlusion arising from atherosclerosis. the most common site of primary thrombosis leading to cerebral infarction is the *carotid bifurcation (origin of MCA+basilar artery). occlusion can also be caused by anterograde progression of the thrombus (may originate from the valvular disease of the heart - endocarditis, etc) or fragmentation/subsequent embolization. occlusion is also associated w/systemic diseases such as DM and HTN.
Term
what are some forms of vascular inflammation which can lead to focal ischemia in the brain?
Definition
arteritis (small/large vessel inflammation seen in syphilis, TB, immunosuppressed pts), PAN+collagen vascular disease (may involve cerebral vessels, causing single/multiple infarcts), primary angiitis of the CNS (small-medium sized parenchymal and subarachnoid vessels w/infiltration by *chronic inflammatory cells+giant cells*), hypercoagulable states (polycythemia vera, sickle cell, CA), dissecting aneurysms (esp w/extra cranial arteries in the neck), and drug abuse (stimulants such as meth or cocaine which are vasoconstrictive)
Term
what is CADASIL?
Definition
cerebral autosomal dominant arteriopathy w/subcortical infarcts and leukoencephalopathy - which is one of the few genetically associated diseases (mutations in *notch 3) w/a *strong link to recurrent strokes and dementia. this is marked by concentric narrowing of the adventitia/media of the leptomeningeal arteries and abnormalities of the white matter. CADASIL is rare, but is considered a hereditary source of strokes.
Term
what characterizes the etiology of emboli which may lead to focal cerebral ischemia?
Definition
entire thrombi or sections of thrombi may break away as emboli in peripheral circulation. these common causes of ischemia/infarct may be due to cardiac mural thrombi, MI (lead to mural thrombi/produce irregularities of blood flow), valvular disease (esp infectious endocarditis), atrial fibrillation (prothrombotic state), carotid artery atherosclerosis, and fat/air/tumor emboli.
Term
where in the brain do emboli generally affect?
Definition
emboli often affect the MCA, which is a direct extension of the internal carotid artery. bifurcations of arteries are common locations for emboli to lodge.
Term
why are emboli hard to ID at autopsy?
Definition
lysis
Term
what are fat emboli?
Definition
fat emboli arise from long bone fracture w/release of bone marrow and fat = widespread *white matter hemorrhages and generalized cerebral dysfunction. this is often seen w/MVA where the symptoms may start off subtle and then rapidly progress.
Term
what are air emboli?
Definition
air emboli may be due to penetrating injury to the cervical vessels (such as w/stab wounds to the neck/upper shoulder), IV injection of air, diving (decreased pressure = liquid nitrogen in blood which can embolize if ascent is too quick), and sex (oral sex on a pregnant woman can cause air emboli as the membranes are more permeable to air).
Term
what are tumor emboli?
Definition
many sarcomas b/c they metastasize by the hematogenous route are able to hitchhike on white blood cells, embolize and produce infarctions
Term
what is asphyxiation?
Definition
*lack of adequate O2 getting to tissues*, which may occur via suffocation, strangulation, or chemically.
Term
what are different forms of suffocation?
Definition
entrapment (inadequate O2 in environment - pts w/this need immediate O2 therapy), smothering (occlusion of the external airway - usually homicidal/suicidal or SIDS), choking (occlusion of the internal airway - natural: epiglottis, homicidal: gagging, accident: inhalation of food/object), mechanical/positional (compression of the body inhibiting oxygenation - often associated w/drugs or alcohol and then congestion/cyanosis/petechiae due to vascular pressure), and suffocating gases (those which displace oxygen).
Term
what are some suffocating gases?
Definition
CO2 and methane which can displace O2 from the atmosphere. if there is an O2 reduction of less than 25% - unconsciousness occurs in seconds and death w/in minutes. this does not produce any specific autopsy findings (sometimes: dusky brain).
Term
what is traumatic asphyxia?
Definition
this occurs when a heavy weight is placed on the upper abdomen/chest - which inhibits lung expansion. congestion and petechiae are often present due to lack of venous drainage.
Term
what are the types of traumatic asphyxia?
Definition
1) overlaying: infant's chest is compressed by parent/sibling/object during sleep. 2) burking: law enforcement sitting on a criminal to subdue them.
Term
what does strangulation refer to?
Definition
mechanical compression of the neck either by hanging (suspension), ligature strangulation (using an implement) or manual strangulation (using hands). it results in compression of the vasculature (carotids/jugulars) and/or the trachea.
Term
what marking is seen commonly on pts who have died from hanging?
Definition
an inverted V shape on one side from the rope
Term
what characterizes the effect of the sleeper (strangle) hold?
Definition
sleeper hold: forearm and biceps compress the neck vasculature - jugular veins will compress first (@ 5 lbs of pressure) causing the face/head to become engorged w/blood (petechiae esp in the eyes). w/10-11 lbs of pressure, the carotids will compress and once this occurs there is about 10 sec of consciousness, past which further compression of 1-2 min = irreversible brain damage and after 3-4 min = death (global brain ischemia).
Term
what characterizes the effect of the choke hold (also a version of strangulation)?
Definition
the anterior aspect of the neck is compressed and if 33 lbs of pressure is applied - the trachea will compress = global brain ischemia
Term
what pathological findings are associated w/death by strangulation?
Definition
petechiae in the sclera/eyelids/around eyes, hemorrhages on the trachea/larynx, and a salmon-purple colored brain (marked vasodilation, deoxygenated blood)
Term
what are some chemical causes of asphyxiation?
Definition
CO, hydrogen cyanide, hydrogen sulfide, and suffocating gases
Term
what characterizes CO as a chemical cause of asphyxiation?
Definition
CO is a colorless, odorless, tasteless gas which competes w/O2 for binding sites on the O2-carrying proteins. tissues affected are discolored cherry-red and in the brain, necrosis of the globus pallidus, cerebral cortex and hippocampus is seen if the pt does not die acutely. pts may die of CO poisoning by accident (often due to heaters since symptoms h/a+n/v are nonspecific) or as a form of suicide (car exhaust in a garage). generally CO levels above 40% are lethal in most pts.
Term
what characterizes hydrogen cyanide as a chemical cause of asphyxiation?
Definition
cyanide produces cellular hypoxia by competing w/the ferric iron atom of intracellular cytochrome oxidase (inhibits electron transport chain). it has been used in suicides and gas chambers though death may not be instantaneous. it smells of burnt almonds, *burns the gastric mucosa and causes pink/cherry red discoloration of tissues (though not as prominent as w/CO). the net effect is lack of O2 to tissues = ischemic brain damage.
Term
what characterizes hydrogen sulfide as a chemical cause of asphyxiation?
Definition
hydrogen sulfide is produced as a byproduct of organic matter fermentation - which is often found in sewers/cess pools. low doses have a rotten egg smell, while high doses paralyze the olfactory nerves and cause rapid death (asphyxiation).
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