Term
| what did reese and karnovsky discover about the BBB? |
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Definition
| horseradish peroxidase (HRP) will not cross the BBB from outside the CSF and if injected into the CSF, HRP will again not cross the BBB and stay contained in the CSF. this was determined to be due to junctional complexes joining the endothelial cells together. |
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Term
| what is the blood / brain barrier? |
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Definition
| the barrier between the blood and extracellular fluid, composed of endothelium |
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Term
| what is the blood / CSF barrier? |
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Definition
| the barrier between the blood and CSF, composed of tight ependyma (epithelium). the choroid plexus is the best example of this. |
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Term
| what is the CSF / brain barrier? |
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Definition
| the barrier between the CSF and extracellular fluid, composed of leaky ependyma (epithelium). this is seen where the choroid plexus invaginates from the wall of the ventricle. |
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Term
| what is the neuronal barrier? |
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Definition
| the cell membrane between the extracellular fluid and intracellular fluid, similar to most other cell membranes. |
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Term
| what is the basic structure of the capillaries in the brain? |
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Definition
| endothelial cells form the capillaries w/tight junctions which are then surrounded by astrocyte processes. |
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Term
| what makes up the meninges? |
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Definition
| the dura mater, the arachnoid, and pia mater |
|
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Term
| what characterizes the dura mater? |
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Definition
| these blood vessels have fenestrated endothelium |
|
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Term
| what characterizes the arachnoid and pia mater? |
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Definition
| these blood vessels are nonfenestrated, have tight junctions and are part of the BBB. |
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Term
| what does a cross-section of the meninges look like? |
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Definition
| the dura mater is at the top and bound tightly to the arachnoid, below which is the arachnoid space which has arachnoid trabeculae/CSF. below this is the pia mater. |
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Term
| what is the virchow-robin space? |
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Definition
| the perivascular space around blood vessels in the brain which is composed of CSF |
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Term
| what characterizes the basement membrane/basal lamina? |
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Definition
| the basement membrane/basal lamina supports the abluminal surface and surrounds the endothelial cells/pericytes. it is composed of laminin, fibronectin, tenascin, collagens, and proteoglycans. it functions in cell attachment/migration and acts as a barrier to macromolecule passage. cell adhesion to the basal lamina involves integrins. |
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Term
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Definition
| cells which regulate endothelial cell proliferation, survival, migration, differentiation, and branching. they are not contractile (lack alpha-actin), have gap junctions which connect w/endothelium, send out projections which cover 20-30% of endothelial circumference (may phagocytize material), and may be derived from microglial cells. |
|
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Term
| what characterizes the astrocytes? |
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Definition
| these envelop 99% of BBB endothelia and adhere to the endothelia via gap/adheren junctions (@ a ~20 nm distance). they help to determine BBB function, morphology, protein expression, and help *guide vessel growth by interacting w/both capillaries and neurons. |
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Term
| what does the BBB restrict? |
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Definition
| large molecules, low lipid molecules, high-electrically charged molecules, and (most) toxins/drugs |
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Term
| why is the surface area of brain micro vasculature so large relative to tissue quantity (100 cm^2/g of tissue)? |
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Definition
| b/c the brain is so metabolically active |
|
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Term
| what is the intercapillary distance in the brain? |
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Definition
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Term
| where is the only place in the brain with less vascularization? |
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Definition
| the watershed zones - more vulnerable to ischemia |
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Term
| what characterizes the effect of tight junctions found in the CNS? |
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Definition
| the lack of endothelial fenestration in brain vasculature creates a high electrical resistance barrier (1500-2000 ohms/cm^2 in pial vessels, 8000 in cerebral microvessels) and low paracellular permeability - however there are ~20 nm clefts between endothelial cells which the junctional complexes maintain the seal on. |
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Term
| what characterizes the junctional complexes found in CNS vasculature? |
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Definition
| these junctional complexes are classified as macula/zona adherens and zona occludens. the adherens junctions are closely opposed membranes w/a junctional complex (cells tightly opposed but not completely fused: ~20 nm). the occludens junctions are composed of fused membrane proteins: occludins (65 kDa proteins which bring the membranes together) and claudins (key proteins which form dimers = primary seal for tight junctions.) |
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Term
| what is the molecular structure of the tight junctions? |
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Definition
| claudins are serpentine proteins which weave in and out of the the cell membranes, fusing to other claudins on adjacent cell membranes. occludins are attached to the intracellular side of the claudins and guide claudin placement. ZO1/2 (zonula occludens) proteins attach the occludins to actin (anchor to cytoskeleton). the ZO1/2 proteins are also bound to the cytoskeleton, kinases, and signal transduction protein (that which affects cell signaling may affect the junctional complex as well). JAMs (junctional adhesion molecules - members of Ig superfamily) are also localized at tight junctions and allow for membrane-membrane communication. |
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Term
| what is the functional significance of the BBB? |
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Definition
| protection, regulation of the CNS: barrier to passage of harmful substances in the blood (kernicterus in newborns), regulation of NTs, ions, growth factors, dietary salt, and water. |
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Term
| why is there a greater number/volume of mitochondria in the BBB as compared to peripheral endothelia? |
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Definition
| this is required for active transport from blood -> brain |
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|
Term
| what characterizes the enzymatic composition of the BBB? |
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Definition
| the luminal membrane is bathed by blood and certain enzymes/transporters (gamma-glutamyl transpeptidase, alkaline phosphatase, and aromatic acid decarboxylase) are present. the abluminal membrane touches the basal lamina and brain tissue and has Na+/K+ ATPase, neutral AA transporter, and GLUT-1. these are necessary to metabolize some neuroactive blood-borne substances as well as maintain polarity across the BBB. |
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Term
| why is BBB capillary thickness ~40% thinner than that of peripheral endothelia? |
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Definition
| so transport may occur quicker |
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|
Term
| what are the 2 main transport mechanisms of the BBB? |
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Definition
| lipid mediation and catalyst mediated |
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Term
| what characterizes lipid mediated BBB transport? |
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Definition
| small lipid molecules (< 700 daltons) can passively diffuse across the BBB |
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Term
| what characterizes the 2 kinds of catalyst mediated BBB transport? is pinocytosis common in the CNS? |
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Definition
| 1) carrier mediated: very quick (milliseconds), active (ATP - used for vitamins/ions) or facilitated (no ATP) transport. 2) receptor mediated: slower (minutes), usual method of transporting proteins such as growth hormone, transferrin, and docosahexaenoic acid. pinocytosis is not a major transport process in the CNS. |
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Term
| where is the blood/CSF barrier? what are the 2 major components of this barrier? what characterizes the CSF? |
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Definition
| the blood/CSF barrier is found in the choroid plexus (makes+maintains CSF) and is found in *fenestrated choroidal capillaries and then *tight junctions between the choroidal epithelium (modified ependyma cells). the choroidal surface area is 1/5000 of the BBB. the CSF has both a secretory and reabsorptive function as there are organic acid+base pumps which remove metabolites from the CSF and put them in venous drainage (reabsorption). |
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Term
| what characterizes the CSF/brain barrier? |
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Definition
| there is leakiness at the base of choroidal plexus (ependyma cells - which line the ventricular cavities). this allows CSF to drain into interstitial brain fluid (ISF) which then interfaces w/venous blood draining the brain. |
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Term
| where in the brain is the choroid plexus located? how does CSF flow from it through the CNS? |
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Definition
| the choroid plexus is located in the lateral ventricle and the roof of the 3rd+4th ventricles. most of the CSF is made in the lateral ventricle and flows either up around the brain or down through the 3rd+4th ventricles and out through the foramen magnum to the spine. |
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Term
| what are the circumventricular organs? |
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Definition
| brain structures such as the choroid plexus which require contact w/peripheral blood for monitoring/normal function. the surface exposed to blood is fenestrated while the surface exposed to the brain around the ventricles has tight junctions. |
|
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Term
| what are the circumventricular organs? where are they located? |
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Definition
| the circumventricular organs (modified capillaries) are the functional interface between the nervous and endocrine system and are mostly found in the 3rd ventricle (thalamus/hypothalamus area). the CVO are: the subfornical organ (below fornix), the lamina terminalis (front wall of 3rd ventricle), the median eminence (on floor off the infundibulum), pineal gland (posterior region of 3rd ventricle), and the area postrema (4th ventricle: area which monitors noxious substances in blood, can initiated vomiting). |
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Term
| how quick is heroin/morphine uptake in the brain? |
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Definition
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Term
| how does L-dopa therapy for parkinson's occur in context of the BBB? |
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Definition
| L-dopa is converted in the brain to dopamine, a NT which is low in parkinson's pts. however the dopamine dose needed in the brain of parkinson's pts should not be systemically administered - so an inhibitor which does not cross the BBB is used, ceasing any conversion of L-dopa to dopamine anywhere else in the body. |
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Term
| how can mannitol be used to reduce intracranial pressure? |
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Definition
| mannitol is a hyperosmotic substance which draws fluid across the brain/blood barrier if the BBB is disrupted. |
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Term
| what is the clinical application of RMP 7? DHA? |
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Definition
| RMP 7, a receptor agonist for bradykinin, is a permeabilizer which temporarily allows passage of anti-tumor therapeutics such as carboplatin into the brain. DHA may also be used in this fashion w/taxol or dopamine (for tardive dyskinesia). |
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Term
| what are flavonoids used to treat? |
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Definition
| MS - flavonoids have a high lipophilicity, allowing BBB passage |
|
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Term
| what is the brain target concept? |
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Definition
| taking a target drug and linking it to a lipophilic substance which allows passage into the brain and once this occurs, is cleaved off. the detached drug is then hydrophilic, allowing it to remain therapeutically in the brain. |
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Term
| what do the meninges cover? |
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Definition
| the entire CNS (eyeballs to tip of spinal cord) |
|
|
Term
| what is the crus cerebri? |
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Definition
| the invagination of the meninges down into the longitudinal fissure |
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Term
| what separates the cerebellum from the cerebral cortices? |
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Definition
| the dura, which in this location is referred to as the cerebellar tentorium |
|
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Term
| what is the function of the various dural sinuses? |
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Definition
| drainage of venous CSF/blood. (CSF has to drain b/c it is constantly being made). |
|
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Term
| what is the dural compartmentalization of the cerebral hemispheres called? |
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Definition
|
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Term
| what is the dural compartmentalization of the cerebellum from the cerebral hemispheres called? |
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Definition
|
|
Term
| what is the partial dural compartmentalization of the partial cerebellar hemispheres called? |
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Definition
|
|
Term
| what is the tentorial notch? |
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Definition
| the space in the tentorium cerebelli through which the brainstem passes - an area which is more subject to herniation if swelling occurs. |
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|
Term
| what layers make up the meninges? what are the spaces/potential spaces? |
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Definition
| the dura (thick collagen) is the outermost, under which is the arachnoid and then the pia which covers the surface of the brain itself (cannot be separated). the dura is bound tightly to the skull and the arachnoid is bound tightly to the dura. the epidural space is the potential space between the dura and skull in the head and a real space between the dura and vertebral periosteum in the spine. the subdural space is a potential space between the dura and arachnoid (usually tightly bound together). the subarachnoid space is a true space in the brain and is where the CSF bathes the brain's surface. |
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Term
| what will usually cause an epidural hematoma? subdural? tx? |
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Definition
| epidural hematoma: tearing of a meningeal artery or of the venous sinus (spreads less, causes more pressure - can cause midline shift of the brain). subdural hematoma: tearing of the cerebral vein as it penetrates the arachnoid and enters sinus (spreads more, less pressure. there is a higher risk for this in elderly pts w/shrinking brains and may be chronic). tx: pressure-releasing hole is drilled in the skull. |
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Term
| how should CSF appear? what is the avg amount? rate of production? what is the normal pressure? |
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Definition
| CSF should appear clear (mainly acellular), most brains have ~ 130 mL, CSF is produced at .5 mL/min, and pressure is 60-100 mm of H2O (divide by 13 to get mm Hg), which keeps the ventricular system open and ensures venous drainage. |
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Term
|
Definition
| swelling of the brain due to increased CSF production/decreased venous drainage |
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|
Term
| what is the function of CSF? |
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Definition
| grossly: mechanical buoyancy/protection. microscopically: nourishing to the nervous system. |
|
|
Term
| where is the CSF produced? |
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Definition
| in the choroid plexus: tufts of capillaries covered by epithelial cells which protrude into the ventricular lumen. |
|
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Term
| what are the landmarks on the lateral ventricle (one of which is in each cerebral hemisphere)? |
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Definition
| the anterior horn (which communicates w/the third ventricle through the interventricular foramen of monroe), body, atrium, posterior horn, and inferior horn |
|
|
Term
| where is the third ventricle located? |
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Definition
| the 3rd ventricle is the midline cavity found in the diencephalon and surrounds the thalamus |
|
|
Term
| where is the 4th ventricle located? |
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Definition
| between the cerebellum, pons, and medulla. it communicates w/the 3rd ventricle via the cerebral aqueduct. |
|
|
Term
| what is typical CSF flow in the brain? |
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Definition
| CSF typically starts in the lateral ventricles, travels through the interventricular foramen (of monroe) to the 3rd, then 4th ventricle. once in the 4th ventricle, CSF can either flow through the medial foramen of magendie to the spinal cord or through the lateral foramen of luschka and circulate around through the subarachnoid space surrounding the brain. cisterns are accumulations of CSF in the brain; the pontine cistern is anterior to the pons and the cisterna magna is below the 4th ventricle. |
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Term
| where is a spinal tap performed? |
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Definition
| a the level of the iliac crest (between L3/L4), which is where the cauda equina is found = allows sampling of CSF. epidurals are also administered here in the free space between the dura and bone found in the spine. |
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Term
| what are the arachnoid granulations? |
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Definition
| tufts of arachnoid villi which pierce the dura and allow drainage of CSF to the venous sinus surrounding the brain (one way valve). these are most common around the longitudinal fissure. |
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Term
| what characterizes the brain's metabolism? |
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Definition
| the brain represents 2% of the body's mass, however it receives 15% of cardiac output and accounts for 20% of O2 consumption. thus the brain has a high metabolic rate which only varied slightly w/state and activity. general anesthesia, hypoglycemic coma and seizures can however significantly alter brain metabolism. |
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Term
| what happens to cerebral blood flow when there is increased partial CO2 pressure in the blood? |
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Definition
| vasodilation and increased flow |
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|
Term
| what happens to cerebral blood flow when there is decreased partial CO2 pressure in the blood? |
|
Definition
| vasoconstriction and decreased flow |
|
|
Term
| what happens to cerebral blood flow when there is increased H+ in the blood? |
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Definition
| vasodilation and increased flow (acidosis depresses neuronal activity) |
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|
Term
| what happens to cerebral blood flow when there is decreased partial O2 pressure in the blood (ischemia)? |
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Definition
| vasodilation and increased flow |
|
|
Term
| what happens to cerebral blood flow when there is increased partial O2 pressure in the blood? |
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Definition
| vasoconstriction and decreased flow |
|
|
Term
| what characterizes intracranial pressure (ICP)? |
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Definition
| normal ICP is 65-150 mm water (5-15 mm Hg, divide by 13). greater than 20 mm Hg is considered elevated, ~40 mm Hg is very dangerous and if as high as 90-100 mm Hg, the cerebral circulation will collapse. |
|
|
Term
| what can cause hydrocephaly? tx? |
|
Definition
| excess production of CSF (papillomas), blockage of CSF circulation (most common), and deficiency of CSF reabsorption. tx: shunting. |
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|
Term
| what are some possible brain herniations resultant from bleeding causing increased ICP? |
|
Definition
| *cingulate gyrus herniation can occur across the longitudinal fissure due to an ipsilateral subdural hematoma. *uncus herniation may occur w/a bleed in the temporal lobe, pushing the parahippocampal gyrus through the tentorium and into the midbrain (may present as papilledema - swelling in optic disc or fixed pupils). *tonsillar herniation may occur if the tonsil of the cerebellum herniates through the foramen magnum due to ICP = compression of the medulla (shut down of cardio/pulm systems). |
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|
Term
| what is cerebral perfusion pressure (CPP)? what role does ICP play? |
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Definition
| CPP = MABP - ICP. as ICP increases, CPP decreases, and if it surpasses MABP, then brain vasculature can collapse. symptoms of increased ICP: headache, papilledema, altered mental status, increased BP (compensatory for ICP), and decreased HR. cushing's triad: increased systolic BP, increased pulse pressure, and decreased HR. |
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|
Term
| what is vasogenic cerebral edema? |
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Definition
| increased BBB permeability increases extracellular fluid. usually responsive to steroids/diuretics. |
|
|
Term
| what is cytotoxic cerebral edema? |
|
Definition
| hypoxia, failure of Na/K pump, increased intracellular fluid/cell swelling. |
|
|
Term
| what is interstitial cerebral edema? |
|
Definition
| increased edema/fluid in white matter around ventricles - usually associated w/hydrocephalus or increased CSF. |
|
|
Term
| what empiric maneuvers lower ICP? |
|
Definition
| hyperventilation on respirator for 24 hrs (increase O2/decrease CO2: causes vasoconstriction and decreased fluid accumulation), elevated head of bed to 30 degrees in midline position (better drainage), and maintain BP (high BP increases ICP and low BP compromises cerebral blood flow). |
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