Cytology of the Nervous System

Question 1

Lewy Body

Answer 1

eosinophilic cytoplasmic inclusions of degenerating neurons in the substantia nigra, pars compacta in patients with Parkinson’s and in cortical and brainstem neurons in patients with certain forms of dementia

**

Question 2

Nigri bodies

Answer 2

eosinophilic cytoplasmic inclusions seen in degenerating neurons in the hippocampus and cerebellar cortex in patients with rabies

Question 3

Tau protein

Answer 3

cross links microtubules

in certain neurodegenerative diseases of the CNS it becomes excessively phosphorylated which prevents cross linking. The affected microtubules form helical filaments which progress to neurofibrillary tangles and senile plaques in the cell body ad dendrites of neurons

Question 4

Neurofibrillary tangles

Answer 4

prominent features of degenerating neurons in ALzheimers disease, amytrophic lateral sclerosis, and Down

**

Question 5

Alzheimer’s

Answer 5

neurons in the limbic system, cholinergic neurons in the basal nucleus of Meynert, and neurons in the cerebral cortex and preferentially affected

Question 6

Loss of dendritic spines

Answer 6

progressive loss occurs with aging and severe loss is associated with cognitive disorders

significant absence of spines in many t ypes of neurons in patients with Down

Question 7

Disruption of fast anterograde transport

Answer 7

may result in an axonal polyneuropathy and may be cause by anoxia which reflects mitochondrial oxidative phosphorylations, or by anticancer agents such as colchicine and vinblastine which depolymerize microtubules

Question 8

Diabetes and axonal transport

Answer 8

hyperglycemia results in an alteration of proteins that form microtubules which may disrupt axonal transport

patients may develop axonal polyneuropathies in long axons in nerves that produce a “glove and stocking” pattern of altered sensation and pain in the feet and then in the hands

Question 9

Retrograde disease infiltration

Answer 9

polio
herpes
rabies
tetanus

retrogradely transported by axons that innervate skeletal muscle

Question 10

Polio and rabies weakness

Answer 10

patients may have weakness of skeletal muscles innervated by affected neurons

Question 11

Tetanus signs

Answer 11

continuous contractions and spasms of axial and limb muscles and spasms of muscles innervated by certain cranial nerves

Question 12

Herpes transport

Answer 12

taken up and retrogradely transported in SENSORY fibers and remains dormant in sensory ganglia

Question 13

Herpes and rabies special feature

Answer 13

both are also transported anterograde

when activated the herpes virus results in painful vesicles corresponding to the distribution of the affected sensory fibers

rabies is transported to salivary glands and is transmitted by saliva after an animal bite

a skunk bit is the most common cause of rabies in US

Question 14

Gap junctions

Answer 14

gap junctions close in damaged neurons and decouple the damaged cells from other neurons in response to a decrease in intracellular pH or elevated intracellular calcium (as in glutamate induced excitatoxicity)

Question 15

Organophosphates

Answer 15

mustard gas and insecticides

binds irreversibly to acetylcholinesterase at the NMJ

ACh accumulates in the synaptic cleft and causes prolonged depolarization of skeletal muscle making it less sensitive to additional ACh release. Death may result from respiratory paralysis

Question 16

Cholinergic neurons in Alzheimer’s

Answer 16

in the CNS, cholinergic neurons in the ventral forebrain (basal nucleus of Meynert) are a main type of neuron that degenerates

Question 17

Glutamate induce excitotoxicity

Answer 17

ichemic neurons in stroke patients may have glutamate induced excitotoxicity in which glutamate accumulations in the synaptic cleft because the uptake process is energy dependent and is slowed by oxygen deprivation

Epilepsy (multiple seizures that arise from excessive neuronal activity in the cerebral cortex) may also cause glutamate induced excitotoxicity of GABA neurons, increasing the likelihood of additional seizures

Question 18

What causes excessive glutamate levels

Answer 18

result from an increase in the influx of calcium into the postsynaptic cell at NMDA receptors. The influx of calcium may result in the production of free radicals in the postsynaptic cell which damages the membranes of its organelles and the plasma membrane. Disruption of the plasma membrane results in an influx of water, which leads to swelling and eventual cell lysis

*Blockage of NMDA calcium receptors that respond to glutamate may be effective in reducing neuronal loss in stroke patients

Question 19

Antianxiety medications

Answer 19

Benzodiazepines are effective drugs that act by enhancing the effects of GABA neurons. Benzos and barbiturates also act as anti epileptic drugs by enhancing GABA inhibition

Question 20

Selective loss of dopaminergic neurons in substantia nigra

Answer 20

results in Parkinson’s disease, a motor disorder of basal ganglia

Question 21

Dopamine in schizophrenia

Answer 21

changes in the levels of dopamine in the mesolimbic and mesocortical circuits may result in the positive and negative symptoms of schizophrenia, respectively

Question 22

Dopamine and drugs

Answer 22

cocaine and amphetamines are addictive substances that act by increasing dopamine levels, particularly in the mesolimbic pathway

Question 23

Depression

Answer 23

changes in the synthesis, release, or activation of catecholamines and serotonin may cause depression, or bipolar disorder, during which patients experience both depression and euphoric episodes

antidepressant drugs include MAO inhibitors which limit the reuptake of catecholamines. Drugs such as prozac selectively block the uptake of serotonin without affecting the reuptake of other catecholamines, and tricyclic compounds (for severe depression) inhibit the uptake of both serotonin and norepinephrine

Question 24

Botulinum toxin

Answer 24

prevents the release of ACh by binding to the presynaptic membrane at the NMJ and at preganglionic autonomic terminals

both skeletal and smooth muscles are affected

patients have weakness initially in muscles innervated by cranial nerves and then weakness in the limbs. Patients also have a dry mouth and abdominal cramping, vomiting, and diarrhea because of an absence of peristalsis

Question 25

Myasthenia gravis

Answer 25

antibodies bind to the nicotinic cholinergic receptors and the receptor complex is engulfed and destroyed, reducing the number of available receptors.

Patients have weakness mainly in skeletal muscles innervated by cranial nerves. 90% of diagnosed patients have ocular weakness and bilateral ptosis. Most patients with MG have a thymoma or thymic hyperplasia.

Curare and bungarotoxin also bind to the nicotinic cholinergic receptors and block NMJ transmission producing effects similar to those seen in patients with MG

Question 26

Lambert Eaton Myasthenic Syndrome

Answer 26

an underlying neoplasm is usually present. Antibodies raised against the neoplasm bind with presynaptic calcium ion channels and disrupt NMJ transmission. Skeletal muscle in the limbs are mainly affected. Sustained contractions of affected muscles lead to an INCREASE in strength

Question 27

Strychnine

Answer 27

an antagonist that binds to and blocks glycine receptors; patients have spasms similar to those infected with tetanus toxin but cranial nerve innervated muscles are spared.

Question 28

Microglia

Answer 28

determine the chances of survival of a CNS tissue graft and are the cells in the CNS that are targeted by the HIV-1 virus. The affected microglia may produce ctokines that are toxic to neurons

CNS microglia that become phagocytic in response to neuronal tissue damage may secrete toxic free radicals. Accumulation of free radicals such as superoxide may lead to disruption of the calcium homeostasis of neurons. The degenerative changes seen in patients with Alzheimer’s disease and in those with MS may be cause by free radical damage result from a progressive inflammatory response caused by microglia.

Question 29

Nodes of ranvier and diabetes

Answer 29

in most patients with diabetes, sorbitol which is normally metabolized from glucose accumulates in nerves and impairs conductance of ion channels and saltatory conduction at nodes of Ranvier

Question 30

Multiple Sclerosis

Answer 30

myelin formed by oligodendrocytes undergoes inflammatory reaction that impairs impulse transmission in axons in CNS

marked by the presence of plaques which are sharply demarcated areas of demyelination. They tend to form in axons that course near the surfaces of the lateral ventricles, in the floor of the fourth ventricle, or near the pail surfaces of the brainstem or spinal cord.

in patients with MS, multiple lesions appear over time but the signs and symptoms may undergo exacerbation and remission, commonly 2 or more CNS sensory or motor neural systems are affected in separate attacks

CSF of patients contains elevated gamma globulin and T lymphs but normal glucose levels

Question 31

Only cranial nerves affected by MS?

Answer 31

optic nerve because all the myelin sheaths of its axons are formed by oligodendrocytes. MS is the most common cause of optic neuritis

Question 32

Guillain Barre

Answer 32

Myelin formed by Schwann cells in the PNS undergoes an acute inflammatory reaction after respiratory or GI illness. This reaction impairs or blocks impulse transmission of axons in PNS resulting in polyneuropathy

Motor axons are always affected, producing weakness in the limbs. Weakness of cranial nerve innervated muscles (most commonly CN VI and VII) or respiratory muscles may be seen. Sensory deficits are mild or absent

Question 33

Glial Neoplasms

Answer 33

astricytomas are the most common form of primary neoplasm in the CNs. In adults 70% are supratentorial. The most common neoplasm is a glioblastoma multiform: malignant astrocytoma. In children, 70% are infratentorial and the most common is a benign cerebellar astrocytoma.

Oligodendrogliomas, ependymomas and microgliomas occur less frequently. Cells of the pia and arachnoid and Schwann cells may give rise to meningiomas and schwannomas.

Primary tumors of the CNS rarely metastasize outside the CNS. Secondary metastases may invade the CNS from primary sites outside of the nervous system

Glial neoplasms are space occupying lesions that may result in an increase in intracranial pressure

Question 34

Drug addiction and the blood brain barrier

Answer 34

heroin, ethanol, and nicotine are lipid soluble compounds that readily diffuse across the blood brain barrier

Question 35

Neoplasms of the blood brain barrier

Answer 35

capillaries that supply primary neoplasms of the CNS are fenestrated and form an incomplete blood brain barrier. These leaky capillaries cause vasogenic edema and increase in CNS interstitial fluid levels. TUmors of the CNS readily absorb contrast materials through the leaky capillaries rendering them detectable by imaging

Question 36

Neuromas

Answer 36

a tangled mass of axonal sprouts may form at the site of a cut axon that fails to regenerate.

Neuromas may cause extreme pain that is resistant to medication

they are associated with phantom limb pain that may arise after amputation