Pathogenesis and physiology Flashcards
What is contained within the gray matter and white matter of the CNS?
Gray matter: High density of neuronal cell bodies
White matter: Axons and associated glial cells
What does spinal cord gray matter contain?
Lower motor neurons, sensory motor neurons and interneurons (gray matter is a central butterfly shape which divides the white matter into funiculi)
What is the composition of gray and white matter in the cerebral hemispheres?
External layer of gray matter with central white matter
What do spinal cord white matter tracts contain?
Ascending sensory nerve fibers, and descending motor fibers
What are the ventricles?
Fluid filled cavities within the CNS. 4 exist: lateral ventricles, third and fourth. Flow of fluid through the ventricles occurs in a rostral to caudal direction
What is cerebrospinal fluid?
An ultrafiltrate of blood
What are the three layers of the meninges?
Pia mater: In direct contact with the neural tissue.
Arachnoid mater: Lies in close contact with the outermost layer (dura mater)
Between which layers of the meninges is the cerebrospinal fluid?
Subarachnoid space.
The space between the arachnoid and dura is a potential space [subdural] containing blood vessels.
What are the falx cerebri and tentorium cerebelli?
Layers of connective tissue that surround the cerebral hemispheres and separate the two cerebral hemispheres and the cerebrum from the cerebellum.
The brain is normally forced caudal or ventral to the tentorium in cases of increased volume.
What is the normal resting potential of cells in the CNS?
-80 mV
How is an action potential propagated in the CNS?
Depolarization occurs through influx of sodium. After passage of the action potential potassium efflux restores a negative resting potential. This is then actively exchanged for sodium ions to return electrolyte concentrations to resting levels.
What is myelin?
A fatty envelope that surrounds axons produced by oligodendrocytes that allows rapid and efficient conduction of action potentials over long distances
Between what arterial blood pressures does CNS perfusion remain constant?
50 - 160 mmHg
What cell plays a key role in matching blood flow to neuronal activity?
Astrocytes
Is CNS perfusion more sensitive to changes in PaCO2 or PaO2?
PaCO2 - a 1mmHg change results in a 5% change in cerebral perfusion. PaO2 needs to fall below 50mmHg for marked vasodilatory effects to occur.
What effect might traumatic brain injury have on PaCO2?
Might decrease ventilatory drive which in turn increases PaCO2 inducing vasodilation of the cerebral vessels. This might increase the risk of herniation.
Aggressive hyperventilation may cause vasoconstriction resulting in ischemia.
What determines cerebral perfusion pressure?
CPP = MAP - ICP
What is the Cushing’s reflex?
In instances of increased ICP the CPP is reduced. This triggers a sympathetic increase in vasomotor tone to try and increase MAP and improve CPP. This systemic vasoconstriction triggers baroreceptors which result in reflex bradycardia. This can be severe.
What is the normal ICP in the dog/cat?
8-15 mmHg. Pressures greater than 15-20 mmHg are considered abnormal.
Increases in intracranial volume can be accommodated to a point (without concurrent changes to ICP) but reductions in CSF production, shifting of CSF, and reducing cerebral blood flow.
What is the blood/brain barrier?
The anatomic and physiologic separation between the CNS parenchyma and general circulation.
Does the blood brain barrier prevent the diffusion of large or small molecular weight molecules?
Large, such as antibodies. Cytokines and certain drugs are able to cross the BBB.
State the antibiotic penetration of various antimicrobials through the BBB.
Thank, F, My, Sister, Can’t, Talk.
What causes ivermectin sensitivity in Collie breeds?
MDR1 mutation in the gene encoding the efflux protein p-glycoprotein that is responsible for removing substances from the CNS.
What are the basic categories of CNS injury?
Contusive, compressive, inflammatory, metabolic, vascular, toxic, degenerative. (Can Cats InVade My Den).
Describe the pathogenesis of contusive CNS injuries
Primary mechanical damage induces secondary injury mechanisms. Secondary injury mechanisms are characterized by increased intracellular levels of calcium, chloride and sodium as ion pumps fail. This results in cytotoxic edema. Extracellular glutamate is also increased due to increased neuronal release and decreased uptake by astrocytes. This worsens intracellular calcium and cell death. Mitochondrial damage results in the release of free radicals. Influx of macrophages causes demyelination. See diagram page 409 Tobias
What is central nervous system injury induced immunodepression?
Reduction in circulating lymphocyte and monocyte numbers, with elevations in ACTH and catecholamines and increased urine cortisol observed after CNS injury.
Describe the pathogenesis of compressive CNS injuries
Decreased local perfusion, obstruction to venous drainage and direct effects of pressure lead to demyelination, edema, axonal degeneration and neuronal necrosis. Decreased venous drainage can result in vasogenic edemia (may be rapidly resolved with glucocorticoid administration). Elevated glutamate propagates injury to oligodendrocytes and causes demyelination.
What is the postulated cause of the clinical deterioration that is sometimes seen following decompression of the CNS?
Iatrogenic injury inflicted during surgery, reperfusion injury.
Is gray or white matter more effected by vascular occlusion (thrombosis or vascular embolization)?
Gray matter.
Ischemia results in similar pathophysiologic changes as those seen following contusive injury (as a result of energy failure).
What is the cause of fibrocartilaginous embolization?
Occlusion of spinal cord arteries or veins with fibrocartilage believed to have originated in the nucleus pulposus of the intervertebral disc
What are the sequelae of hemorrhage in the CNS?
Can be related to contusive injury/reduction in energy supply, compressive injury (if large), or free radical formation from oxidation of iron and copper complexes.
Hemorrhage can be extradural, subdural, subarachnoid, intraventricular, or intraparenchymal.
What cells are particularly important in the modulation of the inflammatory response in the CNS?
Microglial cells (produce a large range of secretory products).
What are the most common neoplasms to metastasize to the CNS?
Hemangiosarcoma, carcinomas and melanomas
What are the two classic types of CNS edema?
Cytotoxic: due to ion influx and cellular swelling (failure of ion pumps). Managed by treating the underlying cause.
Vasogenic: due to increased vascular permeability. Causes extracellular accumulation of fluid, particularly within the white matter. Effectively treated by corticosteroids.
What are the types of intervertebral disc herniation?
Type 1: chondroid degeneration of discs with secondary degeneration of the annulus and eventual nucleus pulposus extrusion
Type 2: Fibrinoid degeneration of discs causing wear and tear of the annulus and protrusion into the spinal cord.
Type 3: Peracute rupture of degenerative intervertebral disc with spread over a large number of vertebrae and no notable center of spinal cord compression.
Acute non-compressive nucleus pulposus extrusions (ANNPE, missle disc, or low volume high velocity): sudden extrusion of normal disc in highly athletic dogs
What is the signalment of patients most frequently affected by type II disc degeneration?
Larger nonchondrodystrophic dogs particularly the German Shepherd and Doberman. Middle aged or older.
Type I degeneration affects small, chondrodystrophic breeds and is associated with younger dogs (5-8 years).
What is myelomalacia?
Rare phenomenon in which damage to the spinal cord progresses after the initial injury.
Most commonly associated with type 1 or type 3 IVDH.
What are some clinical signs associated with progressive myelomalacia?
Cranially directed progression of neurologic signs, paralysis of the intercostal muscles, stress, subnormal temperatures, gastrointestinal disturbances, death.
Can neurons regenerate after injury?
No, but sprouting from neighbouring muscle units can result in reinnervation of a partially denervated muscle.
Oligodendrocytes and astrocytes are able to regenerate (loss of the myelin sheath can be replaced).
What is hydromyelia?
The accumulation of fluid within the central canal of the spinal cord.
Syringomyelia is the accumulation of CSF within the spinal cord parenchyma.
What is hydrocephalus?
The accumulation of fluid within the ventricles.
What are mechanisms by which the CNS can recovery following an injury?
- Synaptic plasticity: upregulation of neurotransmitter receptors, changing of the types of ion channels expressed, formation of new synapses.
- Collateral sprouting and synaptogenesis: new connections between previous synapses and intact pathways.
