week 1- final Flashcards
(93 cards)
1
Q
Uncal herniation
A
Subtype of a Transtentorial herniation that can present with increase ICP and mass effect
Compromise cranial nerve 3–> pupil dilation and impairment of ocular movement at side of lesion.
2
Q
Ex-Vacuo
A
Dilation of the VS with compensatory increase in CSF volume secondary to the loss of brain parenchyma (brain atrophy)
- no block in VS
- See in A disease and Pick disease and HIV
- ICP is NORMAL
3
Q
Hydrocephalus
A
increase in CSF volume = ventricular dilation
- Communicating
- Non communicating (obstructive
- Hydrocephalus mimics
4
Q
Communicating hydrocephalus
A
Decrease in CSF absorption which leads to increased ICP and possibly papilledema and herniation
- resolving meningitis, SAH, and dural sinus thrombosis
5
Q
Non-communicating hydrocephalus
A
Caused by block in CSF circulation. Caused by obstruction by tumors, hematoma, stenosis of aquaduct and colloid cyst blocking foramen of Monro.
6
Q
Normal pressure hydrocephalus (communicating)
A
Affects elderly and is idiopathic. Wet, Wobbly and wacky–> triad of urinary incontinence, ataxia (foot stuck to floor) and cognitive dysfunction.
7
Q
Basal skull fractures
A
Commonly after blows to the side of the head. Serious when compromised petrous portion of temporal bone, external auditory canal and TM.
8
Q
Basal skull fracture PE findings
A
Battle’s sign- retroauricular ecchymosis
Raccoon eyes– bilateral periorbital fractures
CSF drainage due to dural tears through nose
9
Q
Concussion
A
Alteration of consciousness 2’ to head injury by change in head momentum.
- amnesia of event
- low, no reflexes or temp regulation arrest
Due to depolarization of excitatory amino acids mediated ionic fluxes across cell membranes, depletion of ATP and alternation of vascular permeability.
10
Q
Epidural Hematoma
A
Rupture of MIDDLE MENINGEAL A. 2’ to skull fracture! (most common location is pterion)
- Lucid interval (several hours) b4 onset of SS
- Rapid expansion can lead to herniation–> Uncal
- CT shows BICONVEX, hyper-dense blood accumulation that DOES NOT CROSS SUTURES
- Can cause dura to be removed from endoperiosteum
11
Q
Subdural Hematoma
A
Rupture of BRIDGING VEINS.
- Cresent shaped hemorrhage that can cross the suture line
- can cause midline shift
- can be acute (hyperdense) like trauma or chronic (Hypodense) like atrophy, elderly, alcoholism.
12
Q
Pterion made up of what skull bones
A
Temporal, Frontal, parietal and sphenoid
13
Q
Subarachnoid Hemorrhage (SAH)
A
Rupture of an aneurysm
“WORST HEADACHE OF LIFE” thunderclap
- bloody or yellow LP
- rapid time course
- can lead to later (4-10 days) ischemia an vasospasm prevented by NImodipine
-can develop com/obstructive hydrocephalus.
14
Q
Intraparenchymal Hemorrhage
A
Most commonly caused by HTN
- also seen with amyloid angiopathy , vasculitis and neoplasm
- 2’ to reperfusion injury in ischemic stroke
- typically in IC and BG
15
Q
4 glial cells of CNS
A
- Oligodendrocytes- make myelin
- Astrocytes- physical support, repair, K+ metabolism, remove transmitters, Help with Reactive gliosis and derived from neuroectoderm
- Ependymal cells- line ventricular system
- Microglial cells- macrophages of CNS made from mesoderm and mononuclear cells
16
Q
Reactive gliosis
A
Non-specific reactive change in glial cells in response to CNS damage.
- Forms a glial scar made up of reactive astrocytes– most important histo indicatory of CNS injury
- astrocytes undergo hypertrophy and hyperplasia
- cellular swelling
17
Q
Piloid Gliosis
A
aka Rosenthal Fibers which are elongated, granular, hypereosinophilic, proteinaceous deposits seen histo which means LONG STANDING gliosis
- can also be seen in brain tumors
18
Q
Red neuron
A
Seen histologically after actute neuronal injury due to CNS hypoxia or ischemia.
- axonal swelling (spheroids)
19
Q
Permeability of BBB, cognitive impairment vs aging.
A
BBB permeability is more severe with cognitive impairment than aging.
- aging leads to increased BBB perm in hippocampus
20
Q
Molecular velcro of BBB
A
- Cloudins
- Occludins– have a Z0-1 sight that can get phosphorylated and compromise its connection between the occludin and the cytoskelton
- Junction adhesion molecules
21
Q
Pathways through the BBB
A
- Paracellular aqueous pathway
- Transcellular lipophilic pathway– cocaine/Etoh
- Transport proteins– glucose and amino acids
- Transcytosis– LPR-1 trojan horse approach
- Diapedisis– immune cells
22
Q
Monocarboxylate Transporter-1 (MCT1)
A
Transport protein for lactate
- other likes pyruvate, acetate and butyrate
- ketones as well
23
Q
P-Glycoprotein
A
Efflux transporter
- BCRP and Mdr1a/b
- sometimes need to be inhibited to get drugs into the brain without being effluxed out
24
Q
BBB formed by what 3 things?
A
- Tight junctions between non- fenestrated capillary endothelial cells
- Basement membrane
- astrocyte foot processes
25
What makes CSF
Choroid plexus found in 4th ventricle
- makes CSF hyperosmolar and then water follows
- makes about 1/2 of urine made per day
26
Acetazolamide
Carbonic anhydrase inhibitor
| - cant make H+ which is pumped out of cell to blood lumen in exchange for Na+
27
Ouabain
Inhibits Na/K ATPase
28
Furosemide- lasix
inhibits NKCC transporter
29
Glymphatics
Pumping of heart causes arteries in brain to create a convective flow which pushes waste products towards the lymph and venous systems to get ride of them. Cells shrink during sleep and this happens more.
30
ATP usage in Brain
Most by the neurons and next glial cells
| - neurons used about 40% of that for synaptic transmission
31
Brain glycogen storage
Primarily in the astrocytes
- used up when glucose not getting to brain but used up in 4-5 minutes
- twice as much energy as glucose
32
Glucose uses in brain
1. Glycolysis
2. Pentose phosphate pathway-- good for 5c sugars as well as NAPDH which is good for reducing power. However need thiamine for usage (Newborns and alcoholics)
3. TCA cycle
4. Glycogenesis
33
Cerebral metabolic rate- CMR
(A-V)F/W
- Negative value means brain is producing
- Positive value means brain is using
34
2-Dioxyglucose
No -OH at 2
- it can used GLUT transporters and can be broken down by hexokinase
- 2-DG- 6 phosphate which cant be broken down further then we can see what is using glucose the most.
35
Linking of neurovascular unit to blood supply
Glutamate is released from neurotransmitter. Enters the astrocyte via mGluR which increase intracellular Ca2+ which leads to increase in PLA2 and later increase in arachidonic acid. This can either increase PGE2 and EET to cause vasodilation or increase 20-HETE to lead to vasoconstriction which is inhibited by adenosine. Lactate inhibits the reuptake of PGE2 into the astrocyte and thus increases vasodilation as well.
36
Astrocyte- Neuron Lactase Shuttle (ANLS)
80% if glucose in brain is taken up by astrocyte
37
Ketogenic diet
Via fasting or newborns or hibernation
- both D-3 ydroxybutyrate and acetoacetate can produce acetyl Co-A which can enter the TCA cycle
- Can help reduce seizures
38
CSF glucose
should be about 2/3 that of plasma
39
Consciousness
Awake- open eyes, motor arousal
Aware- experience thoughts memories and emotions
- times when you are awake but not aware are partial seizures
- times when you are aware but not awake are during REM sleep
40
Coma
Not awake-- not responsive to anything and unarousable to sternal rub or nail bed roll or other noxious stimuli
Not aware
No emotions
No motor- but can have spinal reflexes
No visual, auditory perception or spontaneous eye movements
- Damage to cerebral hemispheres, brainstem or thalamus
41
Vegetative state
Sleep wake cycle and can open eyes
May smile or grimace or have hand grip reflex
Awake but not aware
Unresponsive to internal and external stimuli
No thoughts memories, emotions or intentions
- intact brainstem but damage to cerebral hemispheres or thalamus
42
Minimally conscious state
Awake and sort of aware (like intoxication)
Can follow commands
Some sleep wake cycles
+/- motor, emotion and awareness
43
Locked- In syndrome
Sleep wake cycles
Intact awareness
Quadriplegia, sensory loss and anarthia
Conscious but unable to interact besides blinking
- Brainstem lesion, usually bilateral pons
44
Level of complement and WBC's in NS
lower levels than usual to control inflammation. Low levels of MHC as well. NS as well las eye and uterus are only parts of body that we consider immunologically privileged.
45
Microglial cells
express high levels of TLR2 and TLR9 which activated T-lymphocytes in an innate response to a pathogen.
46
Is there normal biota in CNS?
No
47
Meningitis SS
More serious when caused by bacteria. Worst of which is Nesseria meningitidis
- present with photophobia
- nuchal rigidity
- headache
- fever with increase WBC in CSF
- rash
48
Neisseria meningitidis
Worst pathogen to cause meningitis.
Gram - diplococci
50% mortality rate even if treated
Give Ceftriaxone as empiric treatment until Nm is ruled out
Can also treat with cipro and rifampin (people of close contacts to pt) and Pen G
- Glucose and maltose fermenters
- rash (non-blanchable) due to thrombocytopenia (intravascular coagulation) DIC
- most common in college kids (vaccine) or others in close quarters
- Respiratory droplets
49
Other players of meningitis
1. Strep pneumoniae--
2. Haemophilus influenzae--
3. Listeria monocytogenes--
4. Crytococcus neoforman-- chronic meningitis
- Bird population especially PIGEONS
- from poop, dried yeast cell spread in wind
- Culture on Sabouraud agar
- soapy bubble lesions on brain
5. Coccidioides immitis
- SW U.S.
- causes osteomyelitis and skin granulomas
- spores into air after earthquake
50
Neonatal/infant meningitis (most commonly via vertical tranmission)
1. Group B strep- mothers screend at 35-37 weeks and given Pen G at labor and gentamicin
2. E. Coli
3. Cronobacter sakazakii-- Gram - bacillis
- most commonly infected baby formula
- 40% mortality
51
Defenses of CNS
Mostly structure
- bony casing
- CSF for cushion
- BBB
52
Sub-acute encephalitis
Symptoms are less striking--> which can smolder for weeks to months
1. Toxoplasms Gondii
2. Measles
3. Prions
53
Rabies
Slow progressive zoonotic disease that can cause fatal encephalitis
- Baltimore IV
- Rhabdovirus- bullet shaped enveloped virus
- Glycoprotein spikes
- inclusion bodies (Negri Bodies) of nerve cells
- 1% survival rate once CNS involved
54
Rabies Symptoms
F, Ha, V, and Fatigue
- Agitation
- disorientation
- seizures and twitching
- Hydrophobia
55
Treat/Prevent Rabies
Treat: RIG immune globulin which are antibodies against Rabies
Prevent: vaccine containing inactivated rabies
56
Polio virus
Acute enterovirus infection of the spinal cord. Neurotropic and thus infiltrate the motor neurons of the anterior horn
- LMN disease
- Flaccid paralysis and myalgia's
- F,Ha, N, ST
- Fecal-oral transmission; replicates in oropharynx as well as small intestine then travels to bloodstream and later CNS
- increase WBC's and slight protein elevation without change to glucose in CSF
57
Tetanus
Caused by Clostridum tenani which is a Gram + endospore forming rod "Lockjaw"
- Found in deep seeded wounds lacking vasculature
- Produces a Neurotoxin (exotoxin) called Tetanospasmin which are proteases that cleave SNARE proteins for neurotransmitters. Blocks release of inhibitory neurotransmitters, GABA and Glycine, from Renshaw cells (inhibitory interneurons) in spinal cord
- SARDONIC GRIN- raised eyebrows with non-genuine open grin (eerie)
58
Tetanus treatment
Antitoxin therapy with booster and muscle relaxants.
- Antitoxin does not affect the toxin already in the neurons
- Pen G and Tetracycline can also be given
59
Botulism
Botulinum is from bad bottles of food and honey (causes a flaccid paralysis).
- Produces a preformed, heat-labile exotoxin that inhibits ACh release at the neuromuscular junction, causing botulism. In adults, disease is caused by ingestion of preformed toxin. In babies, ingestion of spores in honey causes disease (floppy baby syndrome). Treat with antitoxin.
60
Symptoms and treatment for botulism
Diplopia, dysphagia, N, V, and weakness
| - Treat with antitoxin and Pen G for wound since it can be food borne, infant or wound infection.
61
Encephalitis
Is inflammation of the brain that causes HA, F, Altered LOC, Drowsiness, fatigue, seizures and focal neurological deficits.
- caused most commonly by HSV, VZV, post infection, TB, Autoimmune (post-transplant), and enterovirus
62
Other less common players of encephalitis
Arbovirus, HHV-6, EBV, HCMV, JC virus, Rabies, URI, Measles, Mumbs, Bacteria like listeria ,Coxiella and mycoplasma
63
Bacterial CSF
Increase WBC with bands, protein and decreased glucose
- of not the increase protein is due to the fact that the vasculature including the BBB has become more "leaky" due to immune response
64
Viral CSF
Increase WBC's without bands, slight elevated protein and normal glucose
- autoimmune cause very low WBC
65
Suspected encephalitis procedure
Place ALL suspected patients on Acyclovir
- especially with unexplained fever, focal neuro deficits, and seizures
- Get a CT first then get an LP with Diff
- MRI can later be helpful- (identifying ADEM and other forms of post infections)
- Temporal lobe for HSV
- Flaviviruses target BG and Thalamus
66
HSV 1/2
```
Large enveloped virus Baltimore 1
- encode proteins that serve to module host cells and host immune response and proteins to promote viral DNA replication (including DNA dependent DNA polymerase)
```
67
VZV
Most common cause of encephalitis for immunocompromised
| - from shingles or chickenpox
68
Acyclovir
Prodrug that gets activated in body
- Guanosine analogs. Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells (not activated) few adverse effects. Triphosphate formed by cellular enzymes. Preferentially inhibit viral DNA polymerase by chain termination.
69
Post-infectious encephalitis
Measles, mumps, rubella, Vzv, Influenza
- Acute disseminated encephalomyelitis (ADEM)
- inflammatory demyelinating condition from 0-4 weeks post infection
- Type 2 hypersensitivity
- mainly peds
- periventricular inflammation
70
Measles
deadly vaccin preventable disease and NS symptoms can arise in days to years after infection.
- low levels of INFa and IL-2 have trouble clearing infection
- F, HA, Mental status changes, Motor deficit, and seizures
- virus invade brain cells
71
Subacute sclerosing Panencephalitis SSPE
Supportive care- fatal
- age 2 at greatest risk
- symptom free for 6-15 years then have trouble in school, motor dysfunction, seizures, and optic abnormalities
72
Neisseria Meningitidis virulence factors
- IgA proteases which cleaves IgA
- Polysaccharide capsule the defends phagocytosis
- Ferments glucose and maltose
- LOS proteins causes inflammatory response which leads to capillary leakage and hypovolemia and a compensatory vasoconstriction which can cause commonly infarct to the adrenals
73
Waterhouse- Friderichsen
Destruction of the adrenals commonly after a bacterial infection of which you become hypovolmeric and you have a compensatory vasoconstriction which cuts off blood flow to the adrenals. This causes worsening shock and can be fatal
74
aseptic meningitis
Highest in the first year of life.
- no as much neck stiffness and the most common player is Enterovirus
- hand and mouth transmitted
- ssRNA + (baltimore 4)
- Capside and non envelope
75
Nuchal rigidity
TNF and IL-6/ IL-1 tension on the nerve roots passing through the inflamed meninges
76
Ceftriaxone
Transpeptidation of peptidoglycan and inhibits cell wall synthesis.
- Broad spectrum and more seious gram negative -- can obviously cross BBB
- 3 rd generation cefphalsporin
- resistance to beta lactams and change in the penicillin binding protein
77
Strep Pneumoniae
Gram + Cocci Lancet shape
- respiratory droplets
- most common cause of bacterial pneumonia
- alcoholics, sickle sell and splenectomy susceptible
- Encapsulated
- alpha hemolytic
- IgA proteases
- Bile sensitive and optochin sensitive
- Macrolides and Ceftriaxone
- Resistant strain use Vanco
78
Hemophilus Influenza
Gram - coccobacilli
- URI and human only pathogen
- chocolate agar with factor 5 and 10 added
- cherry red epiglottis
- Type B causes meningitis (capsulated polysaccharide)
- ceftriaxone and rifampin for close contacts
- Pili, IgA and endotoxin
79
Group B Strep (Streptococcos agalactiae)
- Gram + Diplococci
- 10-30% vaginal colonize
- causes sepsis, pneumonia, and meningitis
- bacitracin resistant
- Beta-hemolysis
- catalase negative
- Positive CAMP test
- Hydrolyzes sodium hippurate
80
E. Coli
- Gram - Rod
- 20% mortality found with K1 strain
- K Capsule is virulence factor that fights CNS immune system others are LPS endotoxin and fimbrae which not present in CNS bacteria
- Encapsulated prevents fusion with lysosomes
- Lactose fermenter but not sorbital
- catalase positive
- ceftriaxone but can switch to Carbpenem if beta-lactamases present
81
Listeria Monocytogenes
Gram + bacterium, faculative anerarobe
- elderly, Im compromised, fetuses and neo's
- 20% mortality
- deli meats and unpasteurized dairy--> vertical transmission or transplacental
- F, HA and no nuchal rigidity but GI symptoms of D, V, N
- Ampicillin and gentamicin
- Beta hemolytic
- catalase positive
- at body temp motile by actin polymerase
82
Chronic meningitis causes
spirochete, syphillis, leptospira, borrelia bugdoreferi, fungi (cryptococcus neoforman and coccidioides)
83
Mycobacterium tuberculosis
25% of military TB have meningeal involvement
- Gradual onset with generalized illness
- treat with RIPE
84
RIPE
- Rifampin- inhibits DNA dependent RNA polymerase
- Isoniazid- inhibits mycolids
- Pyrazinamide and
- Ethambutol- inhibits cell wall synthesis by binding arabinosyl transferase
85
Amphotericin B
Binds ergosterol creating holes in fungi membrane
86
Flucytosine
Antimetabolite selectively taken up and converted to 5-flourouracine in fungi which interferes with DNA and RNA synthesis
87
Fluconazole
binds fungal p450 enzyme and blocks production of ergosterol
88
Treatment for vasogenic cerebral edema
Steroids and Mannitol
89
Steroids Vasogenic treatment
Dexamethasone which reduces water permeability of tight junctions by decreasing both PGI and PGE which both increase permeability and vascular tone
- Transcriptional regulator
- Decreases VEGF
- Lipophilic
90
Mannitol
- Osmotic diuretic
- increase osmolarity by 11-22 mmol/l
- doesnt cross BBB
- Give IV not orally cause not absorbed
- increased osmolarity in blood pulls water from CSF into blood
91
Treatment for hydrocephalus
1. Get fluid out via shunt
2. surgery to remove tumor or blockage
2. Decrease CSF production
92
Acetazolamide
Carbonic anhydrase inhibitor
- which acts to stop the making of H+ which need to be pumped out of the cell to move Na+ in which is needed to increase CSF osmolarity via osmosis
93
Furosemide
Lasix
| - NKCC inhibitor which is the main pump of solute into the CSF
