CSF and CNS Infections Flashcards
Memorizing normal values may not be that important. But if you want to, they're there. Flashcards for the bacterial organisms causing meningitis (slide 43 of this lecture) are in the CNS Histology and Infections deck.
Review: What makes CSF? What should it look like normally?
Choroid plexus. Clear, colorless.
Normal CSF volume in adults? In neonates?
90-150ml in adults
10-60ml in neonates
What is the rate of CSF formation per day in adults? How long does a complete turnover take?
About 500ml / day (about a water bottle).
-> complete turnover in 5-7 hours.
In what space does the majority of CSF live? What’s the distribution?
Subarachnoid space has majority with 120ml.
Ventricles together have about 30ml.
How does blood flow to the choroid plexus compare to that going to rest of the brain?
It’s about 10x greater.
What are the two stages in CSF creation?
Capillary blood is “ultrafiltrated” across capillary wall / BBB.
Choroid plexus cells transport components into vesicle via isosmotic secretion.
Relative to the blood, what 4 solutes are a present at much lower levels in the CSF?
K+ (not that dramatic)
Amino acids
Proteins (most dramatically - decreased about 3 logs)
Glucose
How does CSF get back into the circulation? What drives this process?
Transcytosis through arachnoid villi/granulations. Increased CSF pressure drives this process.
What are 2 ways in which CSF physically protects the brain?
Floats it - decreasing its effective weight.
Acts as shock absorber - both for impact and sudden changes in ICP.
Why is the brain considered “metabolically fragile”? (2 things) What’s the result of this fragility?
High metabolic rate.
Limited energy stores.
Low threshold for irreversible cellular damage.
Where does the brain get rid of wastes?
In the CSF.
What are the 3 components of the blood-brain barrier (BBB)?
Tight-junctions between non-fenestrated capillary endothelial cells.
Thick basement membrane.
Astrocyte endofoot.
Do endothelial cells of the capillaries comprise the BBB on their own?
Nope. Astrocyte endofoots support the BBB.
What kind of molecules easily get across the BBB? What kind don’t?
Uncharged lipid-soluble molecules get across the BBB easily (e.g. caffeine). Large charged molecules don’t (e.g fibrinogen)
Is the BBB permeable to water?
Yes.
How do important biomolecules that don’t cross membranes well get across the BBB?
Specific transporters.
Is the BBB normally leaky in any areas of the brain? Why or why not? (2 reasons)
Yes, several places. (being leaky the hypothalamus is pretty intuitive)
Being leaky allows brain to sample blood for homeostasis, and allows release of hormones directly into the blood.
What are 4 common conditions for which you would want to evaluate the CSF?
CNS infection
Subarachnoid hemorrhage
CNS malignancy
Demyelinating disease
Review: Where do you do a lumbar puncture (LP)?
Between L3/L4 or L4/L5.
Normal opening pressure for CSF in adults? In children?
90-200 mm H2O in adults (can be up to 250mm normally in obese patients)
10-100 mm H2O in children
What’s a major contraindication to doing an LP?
High ICP, as releasing the pressure in the spinal cord could cause herniation.
What’s the most common complication of LP? Why might it happen?
Headache. Brain not floating as much, doesn’t get shock absorption.
How much CSF do you usually take in an LP?
20ml (probably not that important…)
Why do you take multiple tubes?
Usually you get blood in the first tube from a traumatic tap, despite the patient not having a subarachnoid hemorrhage.
What can make CSF cloudy?
Increased WBCs due to CNS infection
What can make CSF bloody?
RBCs present due to subarachnoid hemorrhage (SAH)
What can produce CSF xanthochromia (discoloration)? (3 things)
Orange -> high beta carotene intake
Brown -> metastatic melanoma
Yellow -> bilirubin from remote SAH
What can make CSF viscous?
metastatic mucinous adenocarcinoma
Normal CSF WBC count?
0-5 cells/ul
Normal CSF RBC count?
0 cells/ul (remember that first tube isn’t reliable value due to traumatic taps)
What’s pleocytosis? What does it indicate?
Elevation of cell counts in CSF. Commonly indicates infection.
What are the normal relative frequencies of WBCs in CSF?
Mostly lymphocytes (40-80%) and monocytes (15-40%). Few neutrophils (0-5%).
Increased CSF neutrophils is associated with what?
Bacterial infections, e.g. meningitis. (and other things)
Increased CSF lymphocytes is associated with what?
Viral infections, eg. meningitis. (and other things)
Normal CSF glucose in mg/dL? More usefully, what percentage of serum glucose should it be?
60 mg/dL. 60% of plasma glucose.
Possible reason for decreased CSF glucose?
Inflammatory cells eat it.
Bacteria eat it.
Normal level of protein in the CSF?
30 mg/dL
4 reasons for increased CSF protein?
Increased BBB permeability.
Increased blood-CSF permeability.
Decreased resorption at arachnoid granulations.
Increased immunoglobulin synthesis in the CNS.
4 microbiological tests you can do on CSF?
Gram stain
Culture
Latex agglutination antigen assay
Nucleic acid assays
What 2 pathogens mentioned can you detect with a latex agglutination antigen assay?
S. pneumoniae
Cryptococcus neoformans (forget that India ink crap*)
*apparently people still use it because it’s fast and cheap.
What’s the best way to test for viruses in CSF?
Look for nucleic acids (PCR, RT-PCR,etc. Way faster than viral culture.)
Does viral or bacterial meningitis have a higher mortality rate? Which is more common?
Bacterial meningitis is much more lethal (~25% morality).
Viral meningitis is 10x more common.
Is all meningitis caused by infections?
No. Certain medications and malignancies can cause meningitis.
5 classic signs/symptoms of meningitis?
Fever Headache Altered mental status Stiff neck Photophobia
3 major classes of viruses that cause meningitis?
Enteroviruses
Herpesviruses (HSV-1, HSV-2, VZV)
Arboviruses (West Nile, St. Louis Encephalitis)
What’s a virus that can cause meningitis in HIV+ people that usually wouldn’t affect healthy people?
CMV (and probably others…)
3 bacterial pathogens that cause HIV-associated meningitis?
L. monocytogenes
T. pallidum
M. tuberculosis
3 fungal pathogens that cause HIV-associated meningitis?
Cryptococcus
Coccidiodes
Histoplasma
What’s the opening pressure, WBC count, cell differential, glucose, and protein levels in the CSF in bacterial meningitis? (i.e. high, normal, low vs. normal CSF)
Opening pressure: High WBC count: Very high Cell differential: PMNs Glucose: Very low Protein: Very high (big picture - everything's very abnormal, PMNs predominate)
What’s the opening pressure, WBC count, cell differential, glucose, and protein levels in the CSF in viral meningitis? (i.e. high, normal, low vs. normal CSF)
Opening pressure: Usually normal WBC count: High Cell differential: Lymphocytes Glucose: Normal Protein: Normal (big picture - mostly normal except for presence of lymphocytes)
What’s the opening pressure, WBC count, cell differential, glucose, and protein levels in the CSF in fungal meningitis? (i.e. high, normal, low vs. normal CSF)
Opening pressure: Variable WBC count: High Cell differential: Lymphocytes Glucose: Slightly low Protein: Slightly high (big picture - changes enough to make you not think viral, lymphocytes make you not think bacterial)
What are 3 different specific molecular/cellular mechanisms by which pathogens enter the CNS? (examples?)
Bacterial adhesion molecules (lipoteichoic acd on S. pneumo binds receptor for platelet activating factor).
“Trojan horse” mechanism (cross BBB inside a monocyte).
Physically disrupted barriers (trauma or neurosurgery)
