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Adv Pathophysiology Unit 2: Neuro of 20

File: advpatho_unit2_1over.pdf Source: C. DeCristofaro, MD

Learning Objectives for this file: 1. Basic overview of nervous system (CNS, PNS, enteric) 2. Neuron functional anatomy 3. Reflex arc 4. Somatic and Autonomic NS THIS FILE IS AN OVERVIEW…DO NOT STRUGGLE WITH THE CONCEPTS RIGHT NOW…USE THIS FILE TO GAIN AN ORGANIZATIONAL CONCEPT MAP and we’ll return to these concepts over and over in the next few files



Why a nervous system (NS) ??? it is in charge of rapid functions & activities, while the endocrine system in charge of slower & long-acting changes… ORGANIZATIONAL OVERVIEW OF NS: CNS, PNS & enteric NS 1. CENTRAL NERVOUS SYSTEM (CNS): • The control center; brain + spinal cord. • Afferent impulses travel from body the CNS & are processed there. • Efferent impulses travel from CNS the body and effector organs. • These impulses travel via well defined pathways called tracts. 2. PERIPHERAL NERVOUS SYSTEM (PNS) • Nervous tissue outside of the CNS • comprised of the somatic (voluntary) + autonomic nervous system (ANS)(involuntary) TWO PARTS: (EACH INCLUDES SENSORY PATHWAYS AS WELL AS OUTGOING MOTOR PATHWAYS) 1) Somatic nervous system

• Connects CNS to our skeletal muscle • Usually refers to actions of organ effectors under our voluntary control. • This system includes both afferent & efferent tracts. • Examples of somatic effectors: (all skeletal muscle) include biceps, bladder sphincter

muscle. 2) Autonomic nervous system (ANS):

• Sympathetic & parasympathetic divisions • both are therefore part of PNS, since the ANS is part of PNS • both afferent & efferent tracts.

NERVE BUNDLES of the PNS: 1) Cranial Nerves:

• both motor & sensory nerves. • There are twelve Cranial Nerves (CN) that exit/enter the CNS via skull foramina.

2) Spinal Nerves: • exit/enter the spinal cord via vertebral bones of spine, through holes called foramina. • They enter/exit at different levels of the spinal column, corresponding to the named

vertebral levels (cervical, thoracic, lumbar & sacral divisions). • Spinal nerves are made up of bundles of both motor & sensory nerves. • These nerves may be part of the somatic (voluntary) or autonomic (involuntary) divisions

of the PNS. 3. ENTERIC NS: neurons in the gut wall (muscular layer & submucous location) • myenteric plexus (of Auerbach) in muscular layer & submucous plexus (of Meissner) • Gut muscle has intrinsic activity independent of the rest of the nervous system • BUT, both divisions of the ANS (sympathetic & parasympathetic) innervate gut for sensory

(e.g. stretch of gut wall) & motor input • neurotransmitter in the gut includes serotonin, VIP, etc. 95% of the body’s serotonin is in the

gut, regulating its smooth muscle function.



SO Remember: we have a CNS & a PNS

FOR THE ABOVE DIVISIONS, REMEMBER THERE IS BOTH MOTOR AND SENSORY Motor:

• Impulses sent from the CNS to the periphery (the “efferent” or “descending” pathway) • Control of the effector organs (muscle, glands)

Sensory:

• Impulses sent from the periphery to the CNS (the “afferent” or “ascending” pathway) • Sending information about the environment of the organs & tissues

PNS Multiple divisions

Somatic (Voluntary)

ONLY Skeletal Muscle

ANS (Involuntary)(Two divisions)

• Smooth & cardiac muscle • Glands

Sympathetic NS • Crisis response • Fight or flight • Catabolic • Counter-regulatory

Parasympathetic NS • Rest & repair • Anabolic • Regulatory

Enteric NS (gut)



Afferent (sensory) & Efferent (motor) pathways

Example – the motor & sensory pathways of the enteric NS:



CELLS OF THE NERVOUS SYSTEM (NS): • Neuron (nerve fiber): Primary cell unit (cell type) of the nervous system (NS) • Neuroglia (Glial cells): supportive cells for neurons • Membranes: overlay NS structures • Note that the neurons affect the function of effector organs (muscles & glands) and thus

interact with non-neurons Neurons interact with EFFECTORS: • Effectors are muscles or glands that actually get the work done in the body • Remember, the neurons only generate electrical impulses to carry information • Or, neurons interact with each other • The interaction with other cells (muscles, glands, other neurons) is via chemicals Three types of neurons: • Sensory nerves

o carry afferent impulses from the body to the CNS (information about the body) o via ascending (incoming information) tracts (pathways)

• Motor nerves o carry efferent impulses away from the CNS to effector organs (cells) of the body

(glands, muscles, blood vessel epithelial cells, etc.) to create changes in the body o via descending (outgoing) tracts.

• Associational neurons o transmit impulses from neuron-neuron (within spinal cord, brain, peripheral ganglia) o Also called "interneurons" (in spinal cord & brain)



NEURON INTERACTION AT THE SYNAPSE: Synapse: where the neurons meet up with the next cell in line • Neurons do not directly "attach" to their neighboring cells, but do transmit their impulses to

their neighboring cells, which may be neurons or effector organs (muscle or glands). • They are separated by the synapse, which is an actual microscopic physical anatomical

space between the terminus of the axon and the next neuron/effector • The first neuron is the presynaptic neuron • The next cell (neuron or effector cell) is the postsynaptic cell • Neuron-to-neuron interaction:

o In order for information to travel from one neuron to another, chemicals are produced by the presynaptic neuron and physically sent across this space to affect the postsynaptic neuron.

o These chemicals are called neurotransmitters. o There are different neurotransmitters found in the different parts of the nervous

system. • Neuron-to-effector interaction:

o Neurotransmitters also produced by the neuron that travel across the synapse to the effector cell (postsynaptic cell)

o This either stimulates (excitatory stimulus) or reduces the functional level of the effector cell (inhibitory stimulus)

o Example: neuron stimulates muscle cell to contract or relax, based on the neurotransmitter (NT) released AND the particular receptor on the postsynaptic cell AND the tissue type and body location of the effector cell

• Although there are a limited number of the typical NTs used by the body (acetylcholine, norepinephrine, epinephrine, dopamine), the effect on the cells is determined by

o the tissue type of the post-synaptic cell o the receptors present on the post-synaptic cell.



NEURON MICROANATOMY AND FUNCTION: Soma: neuron cell body, has dendrites & axon attached. • Cellular constituents of the soma:

o microtubules for transport of neurotransmitters (chemicals made by the neurons that signal nerves & muscle)

o neurofibrils o NISSL substances/bodies (protein synthesis) o Microfilaments for structure

• Nerve impulses: o Impulses are electrical o originate in the soma (neuron cell body) o travel away from the soma towards the next cell (neuron or effector organ) via the

axon • Dendrites: and dendritic processes

o carry impulses one way within the neuron toward the soma (afferent). o Most neurons have multiple dendrites branchings off the soma, some have thousands

of dendrites. o All of these dendrites have the potential to synapse with other neurons, and

thousands of synaptic connections are seen between neurons in the CNS o “dendritic density” has been associated with better CNS functioning (e.g. cognition)

Axons: extension away from the soma, with or without a covering (insulating) myelin sheath. • Originates at the axon hillock; one axon or hundreds of branching axons for one neuron • Carries impulses one way, away from the soma (efferent). Impulses are carried as action

potentials (described below), that begin at the axon hillock. • At the end of the axons, or axon terminus, the axon swells up into synaptic knobs or

terminal buttons (also called boutons). o These contain vesicles that store the chemical neurotransmitters.

• Types of axons – myelinated & nonmyelinated: o Myelinated axons: Larger, faster axons due to insulating properties of myelin

• Myelin made by supportive cells called Schwann cells in the periphery, and glial cells in the CNS (oligodendroglia)

• Example; In the Peripheral Nervous System large motor nerves may be covered with a myelin sheath and a neurolemma (Schwann sheath), interrupted by the nodes of Ranvier (where there is no myelin) go to large skeletal muscles

• Saltatory conduction in myelinated axons because myelin is an insulator more rapid impulse transmission called saltatory ("jumping") conduction

from one node of Ranvier to the next along the axon (see pictures) o Non-Myelinated axons:

• slower conduction (smaller fibers). • No saltatory conduction seen here since there is no myelin. • Example: These types of neurons are found in the peripheral sensory

pathways (pain, temperature). See pictures below…



Support cells: • Neurons need supportive cells

o Astrocyte (Astroglia) : star-shaped cells that provide physical and nutritional support for neurons (clean up debris, transport nutrients, hold neurons in place, digest dead neurons, manage contents of extracellular matrix in which neurons reside

o Microglia: digest dead neurons o Oligodendroglia: provide myelin to neurons in the CNS (Central Nervous System) o Satellite Cells: physical support for neurons in the PNS (Peripheral Nervous

System) o Schwann Cells : make myelin for PNS neurons

• See more: http://learn.genetics.utah.edu/content/addiction/ • Note that all of these support cells may have pathologic conditions – tumors of the NS may

in fact arise from the glial cells themselves (e.g. astrocytoma) Build your own neuron: http://learn.genetics.utah.edu/content/neuroscience/madneuron/

http://learn.genetics.utah.edu/content/addiction/

http://learn.genetics.utah.edu/content/neuroscience/madneuron/



This is a peripheral motor nerve and you can see the myelin on the axon with the nodes of Ranvier that allow for saltatory conduction of the nerve impulse. The electrical impulse will jump from one area that is NOT myelinated to the next area that is NOT myelinated. Jumping is faster than walking…(from the word “saltare” meaning to jump). See more on saltatory conduction below.

Synaptic knobs are on the ends of the axon and contain the neurotransmitter (NT) chemicals

NEURON ANATOMY relates to FUNCTION

Direction of action potential



Saltatory conduction jumping from depolarized node to depolarized node:

Nerve Bundles seen with electron microscope



Sensory Unipolar cell: • a specialized receptor at

one end picks up stimuli from the outside world, or from the internal environment

• it carries the information to the soma and then an axon procees to the CNS in ascending (afferent) nerve tracts

Sensory Unipolar cell: • Compare to the

motor neuron (top picture)

• In the unipolar sensory neuron, the peripheral receptors pick up the sensation, carry the sensation towards the cell body (soma)

• Then, the axon carries the impulse towards the CNS via the ascending (afferent) nerve tracts

Now, compare the unipolar sensory neuron (cell) with the typical motor neuron



BACK TO THE OVERALL NS ORGANIZATION: Remember, the major areas called the Central, Peripheral & Enteric nervous system

Central Nervous System: • by definition, includes the brain + spinal

cord • the peripheral nerves lead out from the

spinal cord at different vertebral levels and are named by this vertebral level, except at the very tail of the spinal cord, which breaks into the cauda equina

• these nerves are also called spinal nerves and exit the vertebral bones via the spinal foramina (foramen means window) -- note that nerves leaving the spinal cord AND entering the spinal cord (sensory nerves coming FROM the body) must use the same opening (foramen).



Motor Tracts • are descending (Efferent) • will decussate (cross over) at

some point so that the impulse originating on one side of the brain has its muscle effects on the contralateral side of the body (for most motor tracts)

• Some are somatic and affect skeletal muscle (voluntary)

• these decussate at the level of the pyramid, and are called pyramidal

• Some are extra-pyramidal (outside the pyramidal tract) and tend to control fine, stereotypic (learned, almost automatic) functions. Disease of these tracts leads to extra-pyramidal symptoms (EPS) such as tardive dyskinesia.

Sensory Tracts • are ascending (Afferent) • will also decussate

(cross over) so that the incoming sensory signal from one side of the body will finally travel to the contralateral side of the brain, although the decussation can occur either immediately on entry to the spinal cord, or further up the pathway in the cord.

• The primary sensory neuron has a peripheral axonal process that connects to the actual part of the neuron that feels the stimulus, and then the impulse travels to the dorsal root to enter the spinal cord via the central axonal process.



HIGHER CENTERS

PARASYMPATHETIC Preganglionic: ACh Postganglionic: • ACh • Nitric Oxide (NO)

SYMPATHETIC DIVISION Preganglionic: Acetylcholine (ACh) Postganglionic:

• Norepinephrine (NE) • Epinephrine (EP) • Dopamine (DA) • Acetylcholine (ACh)



CONTROL & REGULATION – FEEDBACK LOOPS: the NS uses feedback loops. • Feedback Loop:

o a loop contains an incoming part (sensory) and an outgoing part (motor) o The sensory nerve brings an afferent (incoming) impulse to the CNS & efferent

(outgoing motor) messages go out to cause an effect (at the effector organ). • Negative feedback loop:

o the action (or product) of the effector organ sends a message to the CNS (via endocrine or NS pathways) to reduce or stop the initial efferent outflow, thus decreasing the product and/or stop/decrease the effector's action.

o This is the type of feedback seen in most healthy states, maintaining homeostasis. • Positive feedback:

o the action (or product) of the effector organ sends a message to the CNS (via endocrine or NS pathways), to continue efferent outflow, increasing stimulation of the effector organ to produce more product and/or continue/increase the effector's action.

• Clinical correlate: o positive feedback is seen in most unhealthy states, and just a few normal states (in

the coagulation pathway with formation of thrombin causing production of more thrombin, platelet aggregation leading to more platelet aggregation; and the inflammatory response).

If excess or deficiency develops – then corrective actions bring system back to normal



SOME TERMS: (UNFORTUNATELY you will find that these terms are not always used exactly this way !! sorry!!! Due to the historical use of terms not always being the same) • GANGLION:

o Group of neuron cell bodies outside the CNS. o Example: sympathetic chain ganglia that are aligned on each side of the spinal

cord (more on this later). • NUCLEI:

o Group of neuron cell bodies inside the CNS, that are grouped closely together and are responsible for one function.

• REFLEX ARC – not under conscious control: MUCH MORE ON THIS LATER !!! o peripheral or central receptor senses a stimulus (pain, oxygen level, stretch of

arterial wall) o ascending impulse carried by the afferent (sensory) neuron to the spinal cord o synapses in spinal cord (may travel up to CNS as well) o spinal cord sends out descending efferent impulse to an effector organ (motor

neuron, gland). o Simple reflex arc examples:

bladder stretch spinal cord urination (bladder contracts, urethra relaxes)

rectum stretch spinal cord defecation (sphincter relaxation & bowel peristalsis)

Just a picture to illustrate…MORE on this in later file… The simple graphic below is MISSING the ascending dorsal sensory afferent.

Simple patellar reflex:

• in this illustration, the stimulus is stretch of the patellar tendon, that transmits to the spinal cord synapse with interneuron

• spinal ventral motor outflow to the anterior thigh muscle -- this contracts and the lower leg is pulled upward (kicks out)



INTERNEURONAL CONNECTIONS – “NEURON-TO-NEURON”: • Recall that the neurons are separated by a physical space called the synapse • requires chemicals to carry information from one neuron to another • sort of like a relay race from one neuron to another, or a neuron to another cell in the body

(gland, muscle). Example of neuron-neuron connections & neuron-effector cell connections (we’ll go over this in detail in other files – just look at this to get an idea) See actions at the synapse that create neural circuits (pathways) in the brain: http://learn.genetics.utah.edu/content/neuroscience/crossingdivide/

Neurotransmitter Pathways of the Peripheral Nervous System (PNS): made up of the somatic (voluntary, skeletal muscle) and autonomic (sympathetic & parasympathetic).

• all somatic neurons are cholinergic (synapse at the NMJ with nicotinic receptors) • most postsynaptic sympathetic neurons are adrenergic (synapse with alpha or beta

receptors) • most postsynaptic parasympathetic neurons are cholinergic (synapse with muscarinic

receptors)

http://learn.genetics.utah.edu/content/neuroscience/crossingdivide/



SUMMARY of neuron-to-neuron & neuron-to-effector connections: 1. Presynaptic neuron: the first neuron in the relay 2. Postsynaptic neuron: the next neuron in line 3. Types of synapses:

• Nerve to nerve: can be axon/dendrite. • Nerve to effector: are nerve/muscle or nerve/gland when the next cell across the

synapse is an effector organ. 4. NEUROMUSCULAR JUNCTION (NMJ):

• where the neuron from the voluntary (somatic) nervous system synapses with the skeletal muscle that is the effector organ

• carries out skeletal muscular contraction under voluntary control • THIS IS THE ONLY THING UNDER OUR CONSCIOUS CONTROL – control of the

skeletal muscle 5. Transmission of information across the synapse:

• Neurotransmitters are chemicals made by the neuron cell body (soma), are transported down the axon, and released at the synapse, so the first neuron can transmit information across the synapse to the next neuron in line.

• Keep in mind that the impulse is the electrical activity going on in a neuron, and if it is going to send information to another neuron or effector organ, will use a neurotransmitter to do this.

• The effect of the neurotransmitter is to change the electrical charge at the post-synaptic cell, which may or may not cause an impulse to develop in that cell.

• Neurotransmitters can also travel back towards the presynaptic neuron to modulate (control/modify) its function.

6. Neuroglia (“nerve glue”):

• supporting cells of the C.N.S. (include astrocytes, oligodendroglia) support, myelin production

• Schwann cells are the equivalent in the P.N.S. (cover the long motor fibers with their myelin sheath).

• Clinical correlate: o these non-neurons can also give rise to disease states (tumors — astrocytoma,

etc.)



7. Nerve injury & regeneration in the CNS & PNS:

• Axonal sprouting: If the axon is severed, the soma responds with protein synthesis to regrow the axon; partially damaged (e.g., crushed) axons repair more quickly

• Clinical correlate: o If there is a lot of scar tissue or maceration and anatomical derangement (e.g.

trauma, rather than a “clean cut”) regeneration may be impaired o If re-innervation of the muscle is prevented, this causes denervation atrophy

• Neurogenesis: o In general in the mature brain, nerve regeneration (actual mitosis of neural stem

cells) only occurs where new memories must be formed o This is the hippocampus (where new memories are formed and also in the

olfactory bulb where new “smell” memories are formed o See: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339545/ o So if a nerve cell dies, in MOST areas of the mature brain (over age 2 years old) it

is NOT replaced o Repair of damage is based on neuroplasticity

• “remapping” of neural pathways – think of this as a detour around the damaged area (“rerouting” of pathways)

• Remaining healthy cells must take over the functions of the lost cells

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339545/



SUMMARY Overview of Neuron Functional Anatomy: • The SOMA synthesizes neurotransmitter (NT) chemicals • The NTs are shipped down the axon to be stored in the synaptic knobs on the end of the

axon terminal. • This neuron will synapse (meet up) with the next cell in line, called the post-synaptic cell

o The post-synaptic cell could be another neuron, or an effector “end” organ like cardiac muscle, smooth muscle, skeletal muscle, gland).

• The neuron receives input from the dendrites in the form of stimuli o The stimulus could be from another neuron o The stimulus could be from environmental change (heat, cold, pH, pressure,

stretch, etc.) o If the stimuli are sufficient, an action potential develops, so that an electrical

impulse travels down the axon (propagation of the impulse) to the axon terminal. o When the impulse reaches the axon terminal, the impulse causes the release of

neurotransmitters (NTs) from the synaptic knobs. o These NTs then diffuse across the synaptic space and land on the next cell in line

(the post-synaptic cell). • This is how nerve-nerve, nerve-muscle, or nerve-gland communication occurs.

o Remember, the muscle or gland would be called an “effector organ” or “end organ.”

• IMPORTANT to remember is that an NT may result in an inhibitory OR an excitatory effect on the post-synaptic cell, determined by the RECEPTORS on that postsynaptic cell.

o Thus the NT effect may be to stimulate the post-synaptic cell (“excitatory”) o OR, the NT effect may be to reduce the function of the post-synaptic cell

(“inhibitory”) • Although there are a limited number of the typical NTs used by the body (acetylcholine,

norepinephrine, epinephrine, dopamine), the effect on the cells is determined by o the tissue type of the post-synaptic cell o the receptors present on the post-synaptic cell.

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