Chapter 29 Pathogenesis and Physiology of CNS Disease and Injury Flashcards
What are the two broad types of CNS cells
Neurons and glial cells
Name 3 glial cell types and their main function
- Oligonendrocytes: Form CNS myelin sheaths
- Astrocytes: Structural and metabolic support
- Microglia: Innate immune system. Extraneural lineage
What does grey amtter consist of?
and white mater
Grey matter = neuronal cell bodies
White matter = axons and associated glial cells
What is the grey/white matter distribution of brainstem?
Scattered grey matter nuclei with intervening tracts of white matter
Name the four ventricles of the brain and the connceting ducts
- Lateral ventricles (one in each hemisphere)
- 3rd ventricle (midline, ventral to lateral ventricles)
- Fourth ventricle (ventral to cerebellum)
Lateral ventricles –> interventricular foramina –> 3rd ventricle –> mesencephalic aqueduct –> 4th ventricle –> lateral aperture into subarachnoid space OR continues caudally to enter central canal of SC
Where is CSF formed
Choroid plexus of lateral 3rd and 4th ventricles
What are the 3 layers of meninges (out to in)
What maches up pachymeninges?
And leptomeninges?
Dura, arachnoid, pia
Pachymeninges = dura + arachnoid
Leptomeninges = arachnoid + pia
What are the two (potential) spaces between the meninges
Subarachnoid (filled with CSF)
Subdural (potential space for haemorrhage)
Wat is the name of connective tissue separating cerebral hemispheres?
And cerebrum from cerebellum
- Falx cerebri*
- Tentorium cerebelli*
Anatomically speaking, how may the brain herniate?
- Transtentorial (ventral to tentorium)
- Through foramen magnum
T2-weighted sagittal image of the brain showing herniation of the cerebellum through the foramen magnum (long arrow) and transtentorial herniations causing compression of the cerebellum (short arrows).
What is normal resting cell membrane potential?
Intracellular cation?
And extracellular cation
- 80 mV (inside of cell negative)
K+ intracellular
Na+ extracellular
What is the role of myelin?
Allows rapid conduction over long distances while minimizing axonal diameter
At what MAPB is CNS perfusion steadily maintained
50 - 160 mmHg
Graph of autoregulatory control of cerebral blood flow (CBF) and vascular diameter, in response to changes in mean arterial pressure (MAP), arterial partial pressure of oxygen (PaO2), and arterial partial pressure of carbon dioxide (PaCO2).
How does high paCO2 worsed increased ICP?
Increasing PaCO2 –> vasodilation of cerebral vessels –> increased intracranial volume and ICP
What % change in cerebral perfusion if effected by a 1% change in PaCO2?
5%!
ie small Co2 change –> large perfusion change
Below which paco2 level is cerebral ischameia possible (due to vasoconstriction)
<25 mm Hg
What is formula for cerebral perfusion pressure (CPP)
CPP = MABP - ICP
Explain pathophys of cushings reflex
High ICP or low MABP –> ischaemia of neurons in medulla –> increased systemic vasomotor tone –> baroreceptors activated –> bradycardia
If cerebral perfusion pressure drops further –> massive cathecholamine release –> myocardial ischaemi and arrythmias
What is normal ICP
8-15 mm Hg
What components within calvarium determine icp
brain, csf, blood
How can icp be reduced surgically
craniotomy (-15%)
durotomy (-65%)
Where is the choroid plexus blood:brain barrier
between choroid plexus epihelial cells, rather than between capillary endothelial cells (hence normal choroid plexus enhances with contrast)
Which abx have good bbb penetration? And which poor?
What is the new gene name for MDR-1 gene?
Which protein does gene normally encode for
MDR1 = ABCB1
Codes for p-glycoprotein
List 3 features of CNS that make it “immunologically priviledged”
- BBB isolates from immune system
- Poorly developed lymphatic drainage
- Immunosuppressive parenchymal microenvironment
In what two locations does constitutive neurogenesis occur?
Olfactory system
Dentate gyrus of hippocampus
List the potential pathogenesis of CNS injusry (MIIND)
M - Malformations
I - Inflammations
I - Injuries (i.e. compressions, contusions)
N - Neoplasias
D - Degenerative
How is injury to CNS subclassified
- Primary mechanical damage: Brain swelling, hypoxia, diffuse axonal injury
- Secondary injury mechanisms: Biochemical and metabolic changes –> neuronal and glail cell death
What study has been performed.
Describe abnormalities
Cervical myelogram from a Doberman Pinscher with neck pain and tetraparesis that was diagnosed with caudal cervical spondylomyelopathy.
A: Ventral extradural compression of the spinal cord at the C5-C6 intervertebral disc space is obvious with the vertebral column in neutral position.
B: When the vertebral column is extended (B), a dorsal component to the spinal cord compression is visible at dorsal articulation of C5-C6, and a ventral extradural compressive lesion is also visible at the C6-C7 intervertebral disc space. This illustrates the dynamic nature of compression of the vertebral column and highlights the potential for inflicting further spinal cord injury while performing diagnostic tests.
What study had been performed
Describe abnormalities
Lateral view of a myelogram of the thoracolumbar vertebral column of a dog that was hit by a car and presented paraplegic with absent sensation in both pelvic limbs. The intervertebral disc space at the T13-L1 articulation is widened. Contrast medium can be seen filling the substance of the spinal cord over the body of T13, indicating disruption of the spinal cord.
What gene appears to play a central role in ongoing haemorrhae after CNS injury
(N.B. De novo gene expression plays a role in expansion of region of haemorrhage after experimental Sc injury)
Trpm4
List 4 pathologic changes induced by compression
Demyelination
Oedema (usually casogenic, good response to anti-inflmamm dose of steroids)
Axonal degeneration
Neuronal necrosis
Is white or grey matter more severely affected by vascular obstruction?
Grey matter
List 4 ddx for SC embolus
- FCE (dogs)
- Thrombogenic stroke (dogs)
- Feline ischaemic encephalopathy
- Septic embolus
- Neoplastic embolus
- Arthrosclerosis secondary to disorders of lipid metabolism
List 5 sites of CNS haemorrhage
- Extradural
- Subdural
- Subarachnoid
- Intraparenchymal
- Intraventricular
Comment on lymphocytes in CNS
Not usually present. Need to be activated to cross BBB
Give an exampe of a primary CNS malformation that may cause SC inury
And secondary
Primary eg mesencephalic aqueduct malformation – hydrocephalus
Secondary eg vertebral malformations –> compression
Name 5 metabolic conditions relevant to surgeon that may affect CNS
- HE
- PANS
- Uraemic encephalopathy
- Hypoglycaemia
- Neuro signs after feline renal transplant
What are 3 most common neoplasms to metastasise to CNS?
Haemangiosarcoma
Melanoma
Carcinoma
What causes cytotoxic oedema? How is it treated?
And vasogenic oedema?
What is 3rd type? and cause?
Cytotoxic oedema:
- Failure of cell ion pumps –> intracellular swelling with normal BBB. Associated with ischeamia, hypoxia, metabolic disorders, intoxication. Most pronounced in astrocytes.
- Tx: resole underlying cause
Vasogenic oedema:
- Due to increased vascular permeability –> extracellular fluid, esp white matter tracts. Associated with contusion, inflammatory disease, vascular disease, compressive disease.
- Tx: Corticosteroids
Interstitial oedema:
- Abnormal flow of CSF –> extracellular fluid
What is hansen type 1 ivdd
and type 2?
Type 1 = NP (dehydrated) extrusion
Type 2 = protrusion
Remember ANNPE: Peracute extrusions of normal nucleus pulposus material can produce very severe primary injuries; laceration of the dura may be inferred on myelographic images, and, on occasion, extruded nucleus pulposus material can traverse the substance of the spinal cord, leading to widespread hemorrhage and malacia
T2-weighted sagittal magnetic resonance image of the lumbar spinal cord showing hyperintensity within the spinal cord parenchyma overlying an intervertebral disc in which the nucleus pulposus appears smaller than those of the adjacent intervertebral discs. A small amount of material lies within the vertebral canal overlying the disc, causing minimal spinal cord compression. These findings are consistent with herniation of a normal nucleus pulposus.
What is consequemce to muscle if ALL motor neurons lost?
And if only partially denervated?
If all lost –> paralysis
If only partially denervated, sprouting xons from neighbouring motor units can reinnervate denervated part.
N.B. CNS axons and neurons considered irreplacable
which CNS cells can be regenerated
Astrocytes (proliferation + hypertrophy –> astrocytosis/gliosis = “scar”)
and oligodendrocytes
(? microglia)
What structural alteration is often formed where neural tissues have been destroyed?
Fluid filled cavities
Often not associated with functional deficits themselves but progressive accumulation –> pressure
What is meant by:
Hydrocephalus
Hydromyelia
Syringomyelia
Hydrocephalus: Within ventricles
Hydromyelia: Within central canal of SC
Syringomyelia: CSF accumulation within SC parenchyma
Very substantial restoration of the lost function occurs frequently despite considerable tissue destruction. Why is this?
- Synaptic plasticity (i.e. alteration in synapses)
- Collateral Sprouting and Synaptogenesis
(Behavioural adaptations eg spinal walking)
