Traumatic Brain Injury Flashcards
Brain mass is what % of body weight?
2%
Cerebral blood flow is what % of cardiac output?
15%
What is the normal volume of cerebral blood flow?
750 ml/min
Describe O2 consumption by the brain as a % of total body available O2.
20% of total body available O2
Brain requires _________ for energy metabolism.
Glucose
Describe how glucose enters the brain.
Via non-energy dependent carrier-mediated transport across the blood-brain barrier.
__________ is necessary to oxidize glucose to _____ and _____, and _____ is produced via oxidative phosphorylation.
- Oxygen is necessart to oxidize Glucose →
- CO2 and H2O
- ATP is produced via oxidative phosporylation
Besides glucose, what is the alternative energy source for the brain?
- The brain can utilize ketones during starvation to produce 60-70% of the ATP requirement.
- The remainder has to come from glucose via gluconeogenesis.
What causes “complete” or “global” cerebral ischemia?
Cardiac arrest
What causes “partial” cerebral ischemia?
Severe hypotension
What causes “focal” cerebral ischemia?
Embolic occlusion of a single cerebral artery.
What is the zone of injury surrounding an area of complete infarction called?
Penumbra
What are the characteristics of penumbra?
- Partial ischemia and reperfusion
- Delayed cell death vs. viability with or without altered cellular structure or function
- Secondary damage due to inflammation
- Potentially pharmacologically salvageable.
In neuronal injury (i.e. ischemia), sustained deenergization results in intracellular accumulation of what?
- Na+
- Ca2+
Intracellular accumulation of Ca<strong>2+</strong> leads to what?
Ca2+ mediated glutamate release (i.e. glutamate transporter is reversed, glutamate is released from cell to extracellular)
Increased extracellular glutamate results in what?
Increased cellular excitation and seizure activity
How is neuronal injury and glutamate a “vicious cycle”?
Glutamate excitotoxicity results in further Na+ and Ca2+ influx, and thus additional energy failure and cellular compromise.
Sustained deenergization (past neuronal injury) leads to what?
Necrotic cell death
What are the features of necrotic cell death?
- Prolonged elevation of intracellular Ca2+ and Na+
- Early loss of membrane integrity
- Cellular swelling
- Lysosomal rupture
- Cell death within a few hours
What is the “pathway” from ischemia to necrotic cell death?
- Ischemia
- Respiratory inhibition
- ATP depletion
- Glutamate release/Calcium influx
- Elevated cytosolic calcium
- Damage from phospholipases/proteases
- Membrane disruption
- Necrotic cell death
Postischemic mitochondrial Ca2+ accumulation and oxidative stress result in a number of mitochondrial alterations that trigger a cascade of events resulting in what?
Apoptosis
What are the major (general) features of programmed cell death?
- Release of “apoptotic factors”
- Disturbances in mitochondrial gene expression resulting in delayed metabolic failure.
Ischemia/reperfusion results in the increased generation of what?
Free radicals
What is the danger of free radicals produced by ischemia/reperfusion?
- They damage lipids, proteins, and nucleic acids
- They may inactivate key enzymes involved in catabolic and anabolic pathways
Post-ischemic ______________ may promote free radical formation and oxidative stress.
Lactic acidosis
10 minutes of complete ischemia can increase ________ by 500%.
Lactate
After 2 hours of focal ischemia, lactate can increase by >1000% and by 500-700% within the _________.
Penumbra
(T/F) Lactate elevations are increased by hypoglycemia.
False. Elevations in lactate are increased by HYPERglycemia.
Describe neuroprotection as a combination therapy?
Drugs that target Ca2+ influx, Na+ influx, Glutamate efflux, and free radical generation would avoid cell death.
What is the most common cause of death in people <45 years of age?
Trauma
True/False: Severe head injury is associated with a 35% mortality rate.
True.
What are the features of epidural hematoma?
- The hematoma is external to the dura mater
- Often associated with skull fracture
- Fracture of the temporal bone and tearing of the middle meningeal artery results in a rapidly expanding hematoma
- Emergency surgical evacuation is indicated.
What are the features of subdural hematoma?
- Layer of blood between the dura mater and arachnoid
- Results from tearing of bridging veins
- Common with deceleration or shaking injuries
- Common in the elderly
When is surgical evacuation indicated in a subdural hematoma?
If there is mass effect or midline shift.
80% of patients with severe head injury develop what?
Seizures
(T/F) Ongoing seizure activity may further compromise neurons.
True.
What are the products of prolonged seizure activity?
- Prolonged neuronal depolarization
- Increased intracellular Na+ and Ca2+
- Glutamate release
- Oxidative failure and ATP depletion (sound familiar? same features as ischemia)
- Cytoskeletal degeneration
- Microtubule dysfunction
- Protein aggregation
- Clustering of procaspases promoting activating of caspases
- Impairment of neuronal viability
What results in cerebral edema or swelling?
Cerebral injury results in bleeding, vascular injury, cell death and lysis, and alterations in cerebral metabolism that result in edema.
How is edema a “vicious cycle”?
Edema results in increased intracranial pressure causing a decrease in cerebral perfusion leading to more ischemic injury.
How is Cerebral Perfusion Pressure calculated?
CPP = MAP - ICP
- MAP = mean arterial pressure
- ICP = Intracranial pressure
What are the goals of therapy regarding cerebral perfusion therapy?
Keep ICP < 20 mmHg
Maintain CPP > 70 mmHg
ICP > ____ and CPP < ____ are associated with a high morbidity and mortality rate.
- ICP > 25 mmHg
- CPP < 50 mmHg
How is increased ICP treated?
- Sedation and pharmacologic paralysis
- Intubation and mechanical ventilation with modest hyperventilation
- Maintenance of blood pressure
- Osmotic diuretics (mannitol)
- Barbituate coma to decrease cerebral metabolism
Why is hyperventilation an effective treatment for increased intracranial pressure?
As pCO2 is lowered, vasoconstriction decreases diastolic blood flow and lowers ICP.
Why is it important to only use modest hyperventilation to treat increased ICP?
Excessive hyperventilation will result in excessive vasoconstriction and thus result in decreased CBF.
What happens when intracranial pressure reaches a critical point?
- There is downward herniation of the cerebral peduncles through the tentorium cerebelli
- Brainstem compression and loss of cerebral blood flow result in irreversible brain death.
Describe the neurological exam assessment of brain death.
-
Absent Brainstem Reflexes:
- Pupillary light reflex
- Corneal reflex
- Oculocephalic reflex
- Oculovestibular reflex
- Gag reflex
- Apnea
- Flaccid limbs
What are the confimatory tests for brain death?
Negative CBF Studies:
- Angiography
- Radioisotope CBF study
- TCD (transcranial doppler)
EEG (electrocerebral silence)
What abnormality is shown in the following picture?
- Chronic subdural hematomas
- Common in alcoholics
What abnormality is shown in the following picture?
- Diffuse axonal injury (DAI)
- Common with severe injuries
- Often involves brainstem and corpus callosum
What abnormality is shown in the following picture?
- Epidural hematoma
- Associated with skull fracture
- Causes convex (lens) shape
- Usually caused by tearing of the middle meningeal artery
What abnormality is shown in the following picture?
- Subdural hematoma
- Common with deceleration or shaking injuries
- Results from tearing of bridging veins
- Causes concave (crescent) shape
- Common in elderly
