Waqas A. Gill Pathophysiology In-class Quiz - Review Ch.

10 Neurophysiology Understand the functions and components of nervous system o Functions: Sensory input (collection), Integration (computes everything), Control (coordinates action/reaction), Homeostasis (ensures balance), & Mental Activity. o Components: Brain, spinal-cord, nerves, & sensory receptors. o Sub-divisions: i. Central Nervous System (CNS): Brain (+ brain-neurons) & Spinal cord only Interneurons: Connect 1 neuron to another within the CNS. ii. Peripheral Nervous System (PNS): Everything else neuronally-connected. Sensory receptors: Nerve endings or separate, specialized cells that detect: o Temperature, pain, touch, pressure, light, sound, & odors. Nerve: Bundle of axon/sheaths that connects CNS to receptors, muscles, & glands. Cranial nerves: Originate from the brain 12 pairs Spinal nerves: Originate from the spine 31 pairs Ganglion: Collection of neuronal cell bodies outside the CNS (similar to nerves) o Serves as a secondary relay-center that can process senses w/out the brain. Plexus: Extensive network of axons or neuron cell bodies, also located outside CNS Divisions of PNS: a) Sensory (Afferent) pathway: From receptors CNS b) Motor (Efferent) pathway: From CNS Muscles/glands (effectors) i. Somatic: CNS Skeletal muscle (walking) Voluntary, 1-neuron system that uses Synapse (quicker). ii. Autonomic: CNS Smooth muscle (cardiac muscle, sweat glands) Involuntary, 2-neuron system that uses Ganglions (slower). Understand neuronal parts, types, and associated cells o Neurons: Nerve-cells with the unique ability to send/receive electrical signals, and are made up of: Cell body: aka Soma (Nucleus, etc.) Dendrites: Sensory-input (collection) Axons: Sensory-output (conduction away from body) Nissl Substances: Rough ERs needed for proteinproduction for cell-maintenance [Pic: Dark granulations (top-right)] Trigger-zone: Converges dendritic electrical potentials into 1 that flows down the axon. Schwann-cell: Form myelin sheaths around axons between the Nodes of Ranvier.

Classifications of Neurons: Functional classification: Sensory (Afferent): Action potentials toward the CNS Motor (Efferent): Action potentials away from the CNS Interneurons (Association): within CNS from one neuron to another Structural classification: Multipolar: Motor neurons w/ several dendrites & an axon (most neurons in CNS). Bipolar: Sensory neurons with 1 dendritic protrusion & an axon (retina & nose). Unipolar: 1 neuron that divides into 2 branches, 1 of which extends to the periphery and has dendrite-like sensory receptors

o Glial Cells: aka Neuroglia that work to support & protect neurons. The types of glial cells are: Make up the majority of the brain (no electrical signals) CNS a. Astrocytes: Cover neurons, vessels, and pia-mater & utilize microfilaments/tight-junctions to help regulate brain-fluid composition. They hold neurons in place, provide them w/ nutrition (O2), maintain homeostasis & signal transmission and help form the: Blood-Brain barrier: Protects neurons from toxins and regulates nutrient/waste exchange b/w neurons & blood in the brain. This is important b/c the brain takes 20% of cardiac-output (10x more than anything else), so an ion imbalance here is fatal. o Found in Endothelial cells and utilizes gap junctions o Lipophilic substances (ethanol, nicotine, penicillin) can get past this barrier. Reactive Astrocytosis: Proliferation of astrocytes during inflammation, which is good (for protection) and bad (b/c it doesnt allow neurons to repair in areas of replication). b. Ependymal Cells: Line brain-ventricles and the spinal cords central canal, whilst forming: Choroid Plexuses: Secrete CSF w/in ventricles, which is moved around by cilia. c. Microglia: Inflammatory Macrophages Phagocytize necrotic tissue, microorganisms, and foreign substances that invade the CNS (destroy pathogens). d. OligoDendrocytes: Form myelin sheaths around 1 or more axons (electrical insulation) by wrapping several times b/w Nodes of Ranvier (important for Somatic system).

PNS e. Schwann Cells: Wrap around 1 axon several times to form a phospholipid myelin sheath f. Satellite Cells: Surround neuron cell bodies in sensory ganglia (provide support and nutrients).

Organization of Nervous Tissue o White matter: Myelinated axons. Nerve tracts propagate action potentials within the CNS. o Gray matter: Integrates unmyelinated axons, cell bodies, dendrites, & neuroglia. In brain: Gray (outer cortex + inner nuclei); White (deeper tissue Medulla). In spinal cord: White (outer area); Gray (deeper tissue).

Understand permeability characteristics of plasma membrane including channels and their properties Cells produce action potentials, which are electrical properties that result from ionic concentration differences across plasma membranes (affected by relative permeability of membrane). Lipid bilayers, due to their hydrophobicity, help separate charged ions on either side. o Electrical Potential is defined as the net charge across a plasma membrane, so although there may be positive/negative charges on both sides, an unequal ratio will lead to an electrical gradient. o Chemical gradient is the net concentration of ions across a membrane, which alters the concentration gradient. Energy flows down the concentration gradient. Usually, it is the chemical gradient which drives the electrical gradient through ionic charges. Creating these gradients is a slow process of creating stored energy, which we can tap into. o Electrochemical gradients (combining of the 2) give a more accurate description of membrane pot. Resting membrane potential, establishment, changes, and determinants o Resting membrane potential (EM) is the net charge/voltage across the membrane when the cell is at rest, meaning closest to its homeostatic values (Potential Difference: -70 to -90 mV). Ex.) If the outside = 0 mV, but EM = -70 mV, this infers that the inside of the cell is 70 mV more negative than the outside. Several ions (K+, Na+, Cl-, Ca2+) work together to establish the resting membrane potential, but its mainly Na+/K+-pumps and K+ leak-channels that maintain that homeostatic potential. o Depolarization: The potential difference becomes smaller, & Na+ rushes into cell, K+ out, causing it to become less negative (rise). o Hyperpolarization: The potential difference becomes greater, & the cell will lose Na+ and gain K+ as needed to get back to resting pot o Afterpotential: A temporary phenomenon where the loss of Na+ and gain K+ is so quick, that there is a slight hyperpolarization, but the K+ leak-channels quickly bring it back to resting membrane potential o Hyperpolarization: An exaggerated repolarization event (or IPSP) that lowers the overall resting membrane potential to a value lower than -70 mV

Local potential, action potential, refractory period o Local Potentials: Are measurable graded potentials that move in a decremental fashion, but they are not the same thing as action potentials. Summation of graded-potentials can reach threshold. o Action Potential: Electrical properties as a result of ionic concentration differences across a membrane that triggers a depolarization event, which is a temporary, yet intense shift of intracellular polarity (makes internal environment much more positive), which propagates the electrical signal all the way down the axon to its target (CNS or muscle/gland). All-or-none principle refers to the necessity of gradedpotentials to reach threshold before an action-potential will occur (like a camera flash, you either have one or you dont). o Refractory Period: Temporary insensitivity to further stimulation. Absolute: Complete insensitivity during the depolarization/repolarization phase. Cause: Na+ channels already open and stimulated, so a new action potential cannot propagate, since relative concentration ratios are temporarily locked in place. This explains why APs propagate unidirectionally. Relative: Slight insensitivity, where a stronger-than-threshold stimulus must be induced for another AP to initiate. Ion-exchange and linked disorders: Na+/K+-pumps: Use ATP to pump out 3 Na+ ions and pump in 2 K+ ions, thus making the cell lose 1 positive charge, overall. These are Voltage-gated channels that are closed until threshold is met K+ leak-channels: Are always open and help extra K+ ions exit the cell to help maintain gradients. Cl- leak-channels: Are also always open, but Cl- mostly exists in its salt form as NaCl.

o Hyperkalemia: Too much K+ in the blood and ECF, thus leading to K+ staying inside the cell, instead of leaving through the leak channels as it does in normal cases to maintain the -70mv resting potential. This will eventually lead to the resting potential to increase (cell becomes less negative, like an emphasized form of EPSP). o Hypernatremia: Too much Na+ in the blood (usually induced by dehydration). This will not affect the membrane potential, because since theres no Na+ leak-channels, theres no way for Na+ activity to change since its physiological activity is ATP-driven, not concentration-driven. o Hypercalcemia: Too much Ca2+ in the blood, which can lead to decreased neuronal excitability.

Gated Ion-channels: Ligand-gated: Open/close in response to ligands (like Acetylcholine) binding to receptor proteins. Voltage-gated: Open/close in response to small voltage changes across the cell membrane.
(Step 1 of 2) (Step 2 of 2)

Neuronal conduction and modulation of neuronal conduction o Positive Cooperativity: The depolarization of one voltage-gated channel after another, with the previous one influencing the next one.

o Propagation refers to the ability of neurons to mobilize this electrochemical gradient by instantaneously depolarizing 1 part of the axon after another, thus causing a domino-effect of depolarization, which in the grand scheme, is seen as an electrical charge running along the axon.

o The action-potentials will jump from one Node of Ranvier to another, making it faster. Therefore, myelinated axons propagate action-potentials much quicker than unmyelinated axons. o Nerve Fiber Types: Myelinated (faster propagation) vs. Unmyelinated (slower propagation) a) Type-A: Heavily myelinated fibers conduct APs the fastest (15-120 m/s) Provides that instant, sharp pain incurred from injury Motor neurons b) Type-B: Lightly myelinated, so propagation is a bit slower (3-15 m/s) ANS Leads to that dull, continuous pain that settles in a few seconds after sharp pain. c) Type-C: Non-myelinated conduct APs the slowest ( 2 m/s) ANS

o Synapse: The junction b/w 2 cells where APs from a cell can cause an AP in another cell: a) Presynaptic Terminal: AP travels down towards the synaptic cleft, where it attracts Ca2+ ions, which help release neurotransmitters (acetylcholine) from vesicles. They then diffuse out of the synapse and enter the synaptic cleft where they bind to postsynaptic receptors. b) Synaptic Cleft: Open space b/w pre & postsynaptic terminals, where neurotransmitters bind to ligand-gated channels, potentially leading to the 2nd AP propagation. c) Postsynaptic Terminal: Becomes depolarized w/ Na+ as ligand-gated channels are activated, and if threshold is reached, it will fire the 2nd AP. Neurotransmitters and neuromodulators Neurotransmitters: Can be excitatory or inhibitory. o Acetylcholine: A neurotransmitter commonly associated with Ligand-gated Na+ channels in synaptic terminals. o Acetylcholinesterase breaks down: Acetylcholine Acetyl-CoA + Choline, after they unbind from their post-synaptic receptors. The choline is recycled back into the pre-synaptic terminal. o Norepinephrine is released in a similar fashion, except instead of being broken down within the pre-synaptic region (like acetylcholine), MAO will break down norepinephrine once it returns into the presynaptic terminal. o Neuromodulators: Chemicals produced by neurons that modulate APs. Some act by increasing/decreasing the amount of neurotransmitter released by the presynaptic neuron. EPSP: Raises the resting membrane potential to make it naturally more depolarized, thus making future actionpotential easier to reach (Endorphins) IPSP: Lowers the resting membrane potential to make it naturally less depolarized, thus making future actionpotential harder to reach (Hyperpolarization). Presynaptic Inhibition and Facilitation: o Axoaxonic synapses: Axon of one neuron synapses with the presynaptic terminal of another (like many CNS synapses). o Presynaptic inhibition: Reduction in neurotransmitter release from presynaptic terminal (Endorphins can inhibit pain senses). o Presynaptic facilitation: Amount of neurotransmitter released from presynaptic terminal increases (Glutamate facilitating nitric oxide production).

Summation o Spatial-summation: Each dendrite is receiving a different stimulus, so the relative amount of stimulus at each dendrite is considered a graded potential. It is only called an action-potential after the trigger-zone region of the neuron converges all these stimuli into one, leading to their summation, which can create an action-potential. (left pic)

o Temporal summation: Dendrite is receiving 2 stimuli, in quick succession, at the same part of the dendrite, thus leading to summation and the propagation of an action-potential. (right pic) Neuronal Pathways and Circuits o Convergent pathways: Many converge & synapse with smaller number of neurons. Ex. Synthesis of data in brain. o Divergent pathways: Small # of presynaptic neurons synapse with large # of postsynaptic neurons. Ex. Important information being transmitted to many parts of the brain. o Oscillating circuit: Outputs cause reciprocal activation Ex. Sleep cycle, body-pain being induced with no injury