Translational Physiology Block 2 Flashcards
What is a dysraphism?
Incomplete closure of the neural tube
When do the anterior and posterior pores in the neural tube close in humans?
Closure of the neural tube in humans normally occurs between 26 and 28 days of gestation.
What is the most serious dyraphism? Describe it.
anancephaly: the cerebral hemispheres are absent and the rest of the brain is severely malformed. Overlying malformations of the skull, brain coverings, and scalp are present (effects both ectoderm (skin, nervous tissue) and mesoderm (skull))
Which dyraphism of the posterior pore does not result in a pathological condition? Approximately where in the spinal cord is this malformation?
Spina bifibida occulta; fifth lumbar or first sacral vertebra
What is it term used for when the dura and arachnoid membranes herniate (i.e., protrude) through the vertebral defect? if the spinal cord also herniates?
spina bifida cystica; myelomeningocele
What is it term used for when the dura and arachnoid membranes herniate (i.e., protrude) through the cranial defect? if the brain also herniates?
meningocele; cephalocele
What protein is elevated in dyraphisms?
alpha fetoprotein
What are the known causes of dyraphisms?
folic acid deficiency, maternal heat exposure, and polygenic mutations
Describe the steps in axonal degeneration.
Step 1: Synaptic transmission occurring at the axon terminal fails within hours because this complex process is dependent on material provided by axonal transport; Step 2: entire distal segment of axon is destroyed and removed (Wallerian); Step 3: myelin degenerates (Schwann cell may secrete trophic factors that help in recovery); Step 4: macrophages and Schwann cells in the PNS scavenge the debris created by the breakdown of the axon and its myelin; Step 5: After axonal injury, most neuron cell bodies swell and undergo a characteristic rearrangement of organelles called chromatolysis. The nucleus also swells and moves to an eccentric position. The endoplasmic reticulum, normally close to the nucleus, reassembles around the periphery of the cell body. Chromatolysis is reversible if the neuron survives and is able to re-establish its distal process and contact the appropriate target.
What is retrograde degeneration? anterograde?
the neuron that synapses on the injured cell undergoes degeneration; neuron that received synaptic contacts from an injured cell degenerates
What are general symptoms of neuropathies?
numbness (sensory), weakness (motor), parathesias (tingling or pain)
How do neuropathies usually present in patients?
Neuropathies are first presented in the feet (longest axon) and spread upwards and later more proximally
What are two signs of motor neuron injury (LMN) and muscle atrophy?
Fasciculations: muscle cells may twitch in unison. These small twitches can be seen under the skin (result of spontaneous action potential in injured motor neurons); Fibrillations: individual muscle fibers may twitch spontaneously (in the absence of motor neuron (LMN); suggestion that Schwann cells may release acetlycholine)
Understand different types of hydrocephalus, and the location of blockage which would affect the size of the ventricle(s) and drainage
Communicating hydrocephalus occurs when the flow of CSF is blocked after it exits the ventricles. This form is called communicating because the CSF can still flow between the ventricles, which remain open (problem absorbing CSF into SSS through arachnoid granulations); Damage to the arachnoid villi can occur most commonly from infection or inflammation of the meninges or from the presence of an irritating substance, such as blood in the CSF after a subarachnoid hemorrhage (normal pressure hydrocephalus: LP reveals normal ICPs; enlargement of all four ventricles on MRI, characterized by progressive dementia, urinary incontinence, and gait disturbance); Non-communicating hydrocephalus — also called “obstructive” hydrocephalus — occurs when the flow of CSF is blocked along one or more of the narrow passages connecting the ventricles. One of the most common causes of hydrocephalus is “aqueductal stenosis.” In this case, hydrocephalus results from a narrowing of the aqueduct of Sylvius, a small passage between the third and fourth ventricles in the middle of the brain; Hydrocephalus ex-vacuo occurs when stroke or traumatic injury cause damage to the brain. In these cases, brain tissue may actually shrink.
How is hydrocephalus treated?
shunting
Describe a lumbar puncture.
A hollow needle for sampling of CSF can be safely inserted into the subarachnoid space at the level of the L3-L4 interspace (cord ends at L1). With the patient lying on the side, normal (opening) pressure varies from 100 to 180 mm H 2 O (in this position lumbar CSF pressure corresponds to intracranial pressure); Queckenstedt test: gently compressing the external jugular veins in the neck for 10 seconds (rapidly increases intracranial pressure because it increases the volume of intracranial venous blood. It quickly leads to an increase in lumbar pressure)
What can cause increased CSF pressure? What procedure should a physician not do in this case?
CSF pressure can become elevated because of a pathological mass within the cranium, such as a tumor or collection of blood, or because the brain is swollen as a result of injury or infection; i. Attempting a lumbar puncture in these patients is risky, since a small loss of CSF or CSF leak following lumbar puncture can cause brain herniation (pressure gradient that results from low lumbar CSF pressure)
Describe cerebral edema.
increase in BECF where extra fluid comes from intravascular compartment; If the cerebral edema is generalized, it can be tolerated until intracerebral pressure exceeds arterial blood pressure, at which point blood flow to the brain stops; Symptoms: headache, vomiting, altered consciousness; Body responds by raising blood pressure, hyperventilating (alkolosis and vasoconstriction); treatment: mannitol (increases blood osmolarity)
What can cause increased extracellular glutamate? Why is this a pathologic condition?
ischemia, anoxia, hypoglycemia, or trauma; The action of rising levels of extracellular glutamate causes increased uptake of sodium into neurons causing swelling; excitotoxicty also damages astrocytes (swelling resulting from potassium uptake and water)
What is vasogenic edema? What causes it?
Vasogenic edema occurs when there is a leak in the BBB allowing protein to cross drawing water osmotically to increase the volume of BECF and ICF
Know types of glial cells and role of myelin in the CNS
oligodendrocytes, astrocytes, and microglia; myelin speeds up conduction by insulation (saltatory)
Immunopathogenesis of multiple sclerosis
Cell-mediated immunity: CD4 helper 5 cells release cytokines causing tissue damage; Humoral immunity: B lymphocytes secrete autoantibodies and serve as antigen presenting cells; Immunoregulatory cells: decreased activity of regulator cells
Basic pathology of multiple sclerosis
active plaques, multiple areas of demyelination + gliosis + inflammation + initial relative axonal preservation; lymphocyte infiltration: more CD8 cytotoxic T lymphocytes and fewer CD4, beta, and plasma cells
Is remylelination a feature of early MS?
Yes
Does nerve degeneration and axonal loss happen early in MS? Why is primary stage of the disease have milder symptomology to later stages?
Yes; Resolving inflammation, remyelination of axons, and the relative plasticity of the CNS initially compensate for axonal injury (once these fail (much like Diabetes) disease and disability from it become progressive)
What are the major causes of axonal and neuronal loss from MS?
Cortical and meningeal inflammation, Wallerian degeneration, and either ischemia or edema
Know basics of clinical and MRI diagnosis of MS
Dissemination in time, space, or both (more than one T2 lesion, new lesion at follow-up); sites of lesions: periventricular, corpus callosum, cerebellum, juxtacortical (GM-WM junction)); other features: black holes (atrophy), flame-shaped, perpendicular to ventricles and parallel to longitudinal axons, larger than 0.5 cm
How does a physician treat multiple sclerosis?
prednisone (steroid, anti-inflammatory) is used to MS relapses (does not prevent new attacks); Immunomodulators: BG-12, laquinimod, teriflunomide; Reduction in immune cell proliferation: Alemtuzumab; T cell adhesion and transmigration prevention: Natalizumab; future directions: stem cell therapy and remyelination
What are symptoms associated with multiple sclerosis?
sensory and motor deficits, visual loss, ataxia (loss of balance), diplopia, vertigo
Why is gadolinium an important diagnostic tool for MS?
Gadolinium enhancement of a MS lesion on MRI represents BBB damage, which enables infiltration of inflammatory cells into the CNS
How does the length constant change in patients with MS?
Decrease in length constant via a decrease in membrane resistance (axoplasmic resistance unchanged)
A patient complains of blurry vision in their left eye and is diagnosed with optic neurtis? Where is the nerve damage?
Left optic nerve (inflammation); may also cause diplopia (symptoms can be related to MS)
What explains the remission/relapse component of MS?
inflammation attacks (resolution of these attacks)
How can MS, a demyelinating disease, result in gray matter injury?
Axonal injury leading to chromatolysis
Why do MS patients feel relief from their disease burden at cooler temperatures?
Action potential duration is slower at colder temperatures
Would K+ voltage gated channel blockers called aminopyridines be useful in treatment of an MS patient?
Yes, because repolarization would be slowed
What would be the expected result on an EMG of an MS patient?
Normal peripheral conduction velocity
In another inflammatory demyelinating disease, Guillain-Barre Syndrome, the peripheral nervous system is attacked. Would the patients muscle tone and reflexes remain intact?
No; muscle flaccidity and hyporeflexia
What would be the expected findings in the CSF of a MS patient? How are remyelinated axons of different from the from the damaged axons?
elevated IgG levels; Nav1.2 channels may replace Nav1.6 channels in demyelinated axons. Conduction is often barely adequate under normal circumstances and may become inadequate under stressful situations, such as illness, emotional stress, and exhaustion.
What are risk factors for stroke?
hypertension (other cardiac history), smoking, prior stroke, diabetes, blood-borne diseases (sickle-cell), obesity, alcohol (non-modifiabled: age, race, gender, genetics)
Describe major blood flow in the brain.
Anterior circulation: supplies cerebral hemispheres (fed by carotid arteries); posterior circulation: supplies brainstem & occipital lobe (fed by basal artery (anastomose of vertebral arteries)); most arteries are interconnected (anterior and posterior; left and right) by an intact Circle of Willis
What are the different type of stroke?
Hemorrhagic (20%)- 60% ICH, 40% SAH; ischemia (80%)- 20% cardiac embolism, 20% large vessel, 25% lacunar (small vessel) (blood flow is blocked)
What are common causes of ischemic stroke?
arteriosclerosis plaques, atrial fibrillation, other heart failure
What are common cause of hemorrhagic stoke?
hypertension, AVMs, anticoagulants (warfarin) (arteriolar lipohyalinosis results from chronic HTN; more likely to rupture); SAH are caused by ruptured aneurysms
