CNS Pathology Introduction Flashcards
The average brain has over how many neurons? How many synaptic connections?
> 100 billion
150 trillion synaptic connections
The bones of the ______ & _________ protect the CNS from mechanical injury.
Skull ; Vertebrae
The _________ & the ___ separate the CNS from the remainder of the body.
Meninges ; BBB (Blood Brain Barrier)
What are the three classical features of Neurons?
-Nondividing
-Permanent
-Postmitotic
CNS disease symptoms result from what?
Dysfunction of or loss of Neuronal function
What % of total cardiac output goes to the brain?
15%
What % of total bodily oxygen consumption is conducted by the brain?
20%
What % of total bodily glucose consumption is conducted by the brain?
25%
The brain extracts approximately ___% of Oxygen & ___% of Glucose from Arterial Blood in order to facilitate active Neuronal Cells.
50% O2 ; 10% Glucose
Why are Neurons particularly vulnerable to the effects of toxins?
-Fatty nature of Neurons (many organotoxins are fat soluble)
-High activity levels & specialization
-High concentration of Sulfur-Containing AAs (which bind toxic heavy metals)
How do Neurons respond following brain tissue injury?
-Axon &/or Cell Body swell
-Rapid Death results in Phagocytosis (via transformed Microglia)
How do Oligodendroglia respond following brain tissue injury?
-DO NOT REGENERATE (!!)… These cells are typically responsible for myelinating neuronal cells, but do not regenerate upon being damaged.
How do Microglia respond following brain tissue injury?
-Chemotactic Factors activate them & cause them to transform into Phagocytic Cells.
How do Astrocytes respond following brain tissue injury?
-Hypertrophy / Hyperplasia (increase in size & number)… Rxn is called “Gliosis”.
How do Ependymal Cells respond following brain tissue injury?
-DO NOT REGENERATE (!!)… Typically line the ventricles of the brain, but do not regenerate upon being damaged (much like Oligodendroglia).
What differs in the presentation of acute brain injury (vs. damage to other bodily compartments)?
No Fibrotic Scarring (a hole is left instead)
Summarize the “Ischemic Cascade”.
1) Cerebral Blood Flow & Metabolic Demands are mismatched… Can bring about either Electrical Failures or induce Anaerobic Metabolism to kick in.
2) Electric Fail: Na+ Influx into Neurons (ie. Neuron Depolarization) stimulates Ca2+ Influx, leading to activated PLA2. PLA2 enzyme converts membrane phospholipids into Arachidonic Acid, which stimulates both the Cyclooxygenase & Lipooxygenase Pathways. COX Pathway activation leads to Potent Vasoconstriction & Platelet Aggregation, as well as Free Radical production. LPOX Pathway activation induces LT production, which promotes inflammatory response & brings about neuron damage.
3) Anaerobic Metabolism Activation: Induces Lactic Acidosis, as Ketone Bodies are being produced as alternative energy sources. The production of these Ketones causes neuronal damage.
What does “Global Ischemia” mean?
Not enough O2 gets to brain tissues (ie. CHF / ASCVD)
What does “Cerebral Infarct” mean?
-Just means cell death in brain adam
:( the below part is what causes it
Blood Vessel bursts or leaks (Hemorrhagic)
-Blood Vessel blocked by a blood clot, plaque, embolism (Ischemic)
What is an “Intracerebral Hemorrhage”?
Brain bleed (ie. Weak / Malformed Vessel or Trauma)
What is the number one risk factor for Strokes?
Elevated BP
What are some other risk factors for Stroke?
-A Fib
-Diabetes
-Family History of Stroke
-High Cholesterol
-Increasing Age (> 55yrs especially)
-Heart Disease or Poor Blood Flow in Legs
-Fat
-Drink
-Diet
-Smoker
-Illegal Drug Use
-Oral Contraceptive Use
What classes of medications increase one’s risk for suffering a Hemorrhagic Stroke?
-Antithrombotics
-Antiplatelets
-Sympathomimetics (ie. Ephedrine, Pseudoephedrine, Phenylpropanolamine)
What ethnicities have a higher risk for suffering Hemorrhagic Stroke?
-African
-Hispanic
-Asian
What factors increase death risk 30 days Post-Intracranial Hemorrhage (ICH)?
-Lg. Hematoma Volume
-Coma
-Old Age
-Oral Anticoagulant Use
-Increased INR
-Intraventricular / Infratentorial Hemorrhage
Stroke symptoms… What are they?
-Headache (worsens when lying down, bent over, straining, coughing, changing positions)
-Unilateral face drooping / muscle weakness
-Slurred speech
-Loss of bladder / bowel function / coordination
-Dizzy (ie. Vertigo)
-Confusion / Memory Loss
-Sensory changes (ie. Hearing / Taste / Touch / Sight / Pain Sensation)
Ischemic Strokes comprise __% of total Stroke cases; Hemorrhagic Strokes comprise __% of total Stroke cases.
80% (Ischemic) ; 20% (Hemorrhagic)
Would a patient with higher or lower BP have a better prognosis post-Stroke?
Higher BP patient (as overall cerebral perfusion is enhanced with higher BP)
Two patients suffer Ischemic Strokes… One in Mexico (at an outdoor resort), & one in Saskatchewan (outside & during a winter snowmobiling trip). Regarding the temperature differences, which patient has a better prognosis post-Stroke?
The one in SK (as cooler temps slow down brain metabolism & injury extent)
One Stroke patient is hyperglycemic & another Stroke patient is hypoglycemic. Which one has a better prognosis post-Stroke?
The hyperglycemic one (as extent of glucose metabolism affects infarct size)
What visible changes occur around the 5-6hr mark that enable us to distinguish an Infarcted Brain from a healthy one?
-Discoloration & fuzziness brought onto the usually clear border between Gray & White Matter.
At the 72hr mark, what visual difference shows up between an Infarcted Brain & a healthy one?
-Well established Necrosis (that eventually liquifies & leads to holes).
Neuronal Cells begin to die at a Cerebral Blood Flow value below what?
< 10mL / 100g / min
Destructive processes that occur during a Stroke are somewhat reversible if reperfusion of infarcted brain tissues happens within how many hours?
2-4hrs
Within how many hours post-Stroke are the following tPA agents effective:
Alteplase?
IV r-TPA?
Alteplase: 0 - 3hrs
IV r-TPA: 3 - 4.5hrs
Who would be C/I to receive tPA treatments?
-Those with relative bleed risks (including HTN patients).
If tPA is C/I, what other option can be considered? Within what window of time (how many hrs) must it be initiated in order to have effect?
Stent ; 6hr Window
What parameters must be ensured prior to administering tPA?
-No intracranial hemorrhaging
-BP < 185 / 110 (but not too low, as low BP = Poor Perfusion)
If BP is > 185 / 110, what must we administer prior to giving tPA?
One of the below options:
-Labetalol (10-20mg IV)
-Enalapril (1.25mg IV)
-Nitropaste (1-2in)
May repeat the above procedure once if necessary!
Once BP is < 185 / 110, how much tPA should be administered?
0.9mg / kg (with a max dose of 90mg)
-10% should be Bolus over 1min… Remainder infused over 1hr.
How long after tPA administration should we withhold Antiplatelet Therapies or Heparin?
24hrs
Why is a single bolus dose of tPA favored over a 1hr infusion?
-Longer DOA due to less Plasminogen Activator Inhibitor inactivation.
-Thought to work better for large clots.
How do we treat Hemorrhagic Stroke?
1) BP ctrl & supportive care (primary goal is reduce intracranial pressure)
2) Anti-Clotting agents in order to further reduce risk
How do concussions & contusions differ in presentation?
Concussion: Widespread & microscopic bruising / bleeding
Contusion: Localized & macroscopic bruising / bleeding
What is a laceration?
Tissue tearing
What are some events that can bring upon Intracerebral Hemorrhages?
-Head Trauma Complications
-Intracerebral Vessel Rupture
-Gunshot Wound
-Nontraumatic Forms (ie. Stroke)
-Hematologic Disease (ie. Leukemia)
What types of virally-induced diseases can cause Encephalitis?
-Rabies
-Polyomelitis
-Herpes Encephalitis
-MMR
-West Nile Disease
How do mild & severe cases of Encephalitis differ in presentation?
Mild: Flu-like symptoms, headaches.
Severe: Severe headaches, high fever, drowsiness, vomiting, confusion, seizures, abnormal sensations or movements.
Four types of Encephalitis?
