Physiology Review PDF

The Nervous System Introduction CNS vs. PNS The nervous system, comprising the central nervous system (CNS) and peripheral nervous system (PNS), coordinates behavior and transmits signals. It includes the brain, spinal cord, nerves, peripheral ganglia, sympathetic and parasympathetic ganglia, an...

The Nervous System Introduction CNS vs. PNS The nervous system, comprising the central nervous system (CNS) and peripheral nervous system (PNS), coordinates behavior and transmits signals. It includes the brain, spinal cord, nerves, peripheral ganglia, sympathetic and parasympathetic ganglia, and the enteric nervous system, a semi-independent system which controls the gastrointestinal system. The mammalian nervous system consists of two main subdivisions: the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and spinal cord, while the PNS consists of sensory and motor neurons. The peripheral nervous system (PNS) is divided into sensory and motor subsystems. Motor subsystems consist of somatic and visceral efferent neurons that carry action potential commands to skeletal muscles and peripheral neurons controlling smooth muscle and some glands, while sensory subsystems involve afferent neurons transmitting stimuli. Spinal and cranial nerve sensory components consist of axons of somatic afferent neurons, which carry action potentials from various receptors. Visceral afferent neurons carry action potentials from stretch receptors or chemoreceptors. Most afferent and efferent axons are part of the autonomic nervous system, responsible for involuntary control of muscle, glands, and physiological functions. Peripheral nerve axons connect trunk and limb regions to form a single spinal nerve at intervertebral foramina. Afferent sensory and motor axons enter and exit the spinal cord, while cranial nerves run through skull foramina. PNS axons can regrow slowly post-injury. Damaged CNS axons fail due to local environment's inhibitory features. Glacial cells inhibit CNS neuron regeneration. CNS Division Six major regions: spinal cord, five brain regions (medulla, pons, midbrain, diencephalon, telencephalon). Cerebellum, dorsal to pons and medulla, sometimes a seventh major region. Brainstem: medulla, pons, midbrain. Forebrain: diencephalon and telencephalon. The spinal cord, brainstem, and forebrain form a hierarchy of functional organization. The spinal cord receives sensory input and supplies motor output, while the brainstem performs functions for the face and head. The forebrain processes sophisticated information and formulates motor commands. The brainstem can send motor commands directly to the spinal cord, while tracts are bundles of axons. Spinal Cord: The spinal cord, the most caudal region of the CNS, contains sensory dorsal root axons, motor neurons, sensory information to the brain, and motor commands from the brain to motor neurons. It controls simple reflexes like muscle stretch reflexes and limb withdrawal from painful stimuli, even when disconnected from the brain. Medulla: The medulla, a part of the brain, receives and sends information from sensory receptors and motor commands to skeletal and smooth muscles. Its cranial nerve nuclei, which collect medullary neurons' cell bodies, play a crucial role in respiratory and cardiovascular systems, feeding, and vocalization. Pons: The pons, located rostral to the medulla, contains numerous neurons that transmit information from the cerebral cortex to the cerebellum, crucial for smooth movement and motor learning. Its cranial nerve nuclei play vital roles in sensory information and chewing control. Midbrain/Mesencelaphon: The midbrain, located rostral to the pons, contains superior and inferior colliculi for processing visual and auditory information, cranial nerve nuclei for eye movement, and periaqueductal gray for endogenous analgesia control. Each region contains axon tracts carrying action potentials to or from the forebrain and spinal cord. Nuclei, aggregates of CNS neuronal cell bodies, give rise to tract axons. Each region also contains reticular formation, a complex of smaller nuclei and loosely organized axonal projections in the brainstem core. Diencephalon: The diencephalon, comprising the thalamus and hypothalamus, is a large structure that relays and modulates information from sensory systems to the cerebral cortex, regulates the autonomic nervous system, and plays a crucial role in homeostasis. Telencephalon: The telencephalon, also known as the cerebral hemispheres, comprises the cerebral cortex, basal ganglia, and hippocampus. The cortex mediates sensory integration, conscious perception, and voluntary movement. The basal ganglia regulate motor functions, while the hippocampus is crucial for memory and spatial learning. Meninges Pia mater: Single layer of fibroblast cells connected to brain and spinal cord. Arachnoid: Thin layer trapping cerebrospinal fluid in subarachnoid space. Dura mater: Thicker layer protecting CNS, often fused with bone inner surface. Cerebrospinal Fluid A clear, colorless fluid found in the subarachnoid space, central canal of the spinal cord, and ventricular system of the brain. Produced primarily in the ventricles of the brain. Flows from the ventricles into the subarachnoid space, bathing the surface of the CNS. Dynamic; replaced several times daily. Determinant of the neuronal microenvironment, carrying away metabolic waste and harmful macromolecules. Serves as a diagnostic tool for CNS infection, inflammation, or tumor activity. Forms a fluid-filled, membranous container within which the CNS "floats." Cranial Nerves Cranial nerves are a set of 12 paired nerves that originate directly from the brain. They are responsible for a variety of functions, including sensory and motor activities in the head and neck. 1. Olfactory Nerve (CN I): Responsible for 3. Oculomotor Nerve (CN III): Controls the sense of smell. most of the eye’s movements, including 2. Optic Nerve (CN II): Responsible for constriction of the pupil. vision.  4. Trochlear Nerve (CN IV): Controls the 8. Vestibulocochlear Nerve (CN VIII): movement of the eye, specifically Responsible for hearing and balance. looking down and towards the nose. 9. Glossopharyngeal Nerve (CN IX): 5. Trigeminal Nerve (CN V): Provides Provides taste for the back one-third of sensation to the face and controls the the tongue and helps with swallowing. muscles used for chewing. 10. Vagus Nerve (CN X): Controls the 6. Abducens Nerve (CN VI): Controls the heart, lungs, and digestive tract. movement of the eye, specifically 11. Accessory Nerve (CN XI): Controls the looking outward. muscles used in head movement. 7. Facial Nerve (CN VII): Controls facial 12. Hypoglossal Nerve (CN XII): Controls expressions, and provides the sense of the muscles of the tongue. taste for the front two-thirds of the tongue. https://youtu.be/GJBnwZQ60Ss https://www.youtube.com/watch?v=5W42zRbrXXU The Neuron Nervous System Cells Neuron: Basic functional unit of the nervous system. Glial Cells: - Maintain structural and functional integrity of neurons. - Support neurons, modulate neural communication, development, pathology, and repair. Neuron numbers vary greatly, from 100 million in small mammals to over 200 billion in whales and elephants. Glial Cell to Neuron Ratio: ≃1:1 to 10:1 - (varies across brain regions) Neurons and Information Communication Neurons are fundamental building blocks for communication using chemical and electrical signals. They possess specialized properties for information reception, processing, and transmission. Cell membrane is electrically excitable, and neuronal shape and size vary. Common functions include impulse generation, converting incoming information into electrical potential. Neuron Roles and Functions Dendrites: - Receive signals from other neurons' presynaptic terminals. - Branch-like extensions of cell body. - Major receptive apparatus of neurons. - Contains special receptor proteins for signal reception. Cell Body: - Integrate opposing signals on the axon's initial segment. - Cell body manufactures proteins for neuron maintenance. Axon: - Transmit action-potential impulses along the axon. - Conducting unit of neurons, transmitting electrical impulses. - Lack ribosomes, unable to synthesize proteins. - Macromolecules created in the cell body are carried to distant axonal regions and presynaptic terminals by axoplasmic transport. Presynaptic Terminals: - Signal adjacent cells from the presynaptic terminal. - Presynaptic terminals branch into specialized endings. - Transmit chemical signals upon arrival of action potential. - Terminals usually contact neuron's dendrites or cell body. - Contact can occur for presynaptic inhibition.  Synapse: - Site of contact between presynaptic terminal and adjacent cell. - Forms by presynaptic terminal of one cell, receptive surface of adjacent cell (postsynaptic cell), and synaptic cleft. - Presynaptic terminals contain synaptic vesicles releasing neurotransmitters. - Presynaptic terminals often synapse on dendritic spines on neurons. - Postsynaptic cell receptive surface contains specialized receptors for neurotransmitters released from presynaptic terminal. Myelin - Large axons surrounded by myelin, a fatty, insulating coating. - Schwann cells and oligodendrocytes form myelin in peripheral and central nervous systems. - Ranvier nodes interrupt myelin sheath at regular intervals. - Myelin sheath and Ranvier nodes increase action-potential conduction speed. Functions corresponding to the nervous system's role: collecting, integrating, and producing output to change the environment. Cell Body Role in Protein Manufacturing Nucleus: blueprint for protein assembly. Free Ribosomes: Assemble cytosolic proteins. Rough Endoplasmic Receptulum: Assembles secretory and membrane proteins. Golgi apparatus: Processes and sorts secretory and membrane components for transport. Lysosome and proteasome: Degrade used, damaged, or surplus proteins. Neuron Signaling Functions Receptors receive neurochemical signals from presynaptic terminals of other neurons.  These signals are transduced into small voltage changes and integrated into action potential on the axon. The action potential travels rapidly to distant presynaptic terminals, triggering the release of chemical neurotransmitters onto another neuron or muscle cell. Neurons and Electrical Potential Neurons and muscle cells have an electrical potential measured across their cell membrane. The magnitude and sign of this potential can change due to synaptic signaling or environmental energy transduction. When the membrane potential reaches a threshold, an action potential occurs, moving rapidly along the neuronal axon. Resting State: The neuron is at rest with a negative charge inside and a positive charge outside. Threshold: A stimulus causes the neuron to reach a threshold potential, usually around -55 mV. Depolarization: Voltage-gated sodium (Na+) channels open, allowing Na+ ions to rush into the cell, making the inside more positive. Peak: The inside of the neuron becomes positively charged, reaching about +30 mV.  Repolarization: Sodium channels close and voltage-gated potassium (K+) channels open, allowing K+ ions to flow out, restoring the negative charge inside. Hyperpolarization: The neuron temporarily becomes more negative than its resting state due to the continued outflow of K+ ions. Restoration: The sodium-potassium pump restores the original ion balance, returning the neuron to its resting state. This process allows neurons to transmit electrical signals rapidly and efficiently123. Action potential originates at the initial segment and spreads down the axon. Na+ ions influx during action-potential depolarization leads to positive charges spreading to adjacent membrane segments. This migration, called electrotonic current, depolarizes adjacent segments to threshold, opening voltage-gated Na+ channels. Action potential develops, triggering a cycle in adjacent membranes and down the axon.  Action potential spreads from the axon's initial segment to the presynaptic terminal. Action Potential Conduction Velocity in Axons Speed varies based on internal diameter and myelination degree. Small-diameter, unmyelinated axons have slow conduction velocity (0.5 m/s). Large-diameter, heavily myelinated axons have conduction velocities over 90 m/s. Passive Electrotonic Current and Action Potential in Axonal Membrane Passive electrotonic current triggers action potential at adjacent axonal patches. Faster and farther travel along wider axons or myelinated patches. Ion exchange in myelinated axons occurs at bare nodes of Ranvier. Rapid spread of electrotonic current and slower ion exchange at nodes cause action potential to jump from node to node. The Synapse Chemical and Electrical Synapses in the Central Nervous System Chemical synapses are all synapses in the central nervous system. The first neuron secretes a neurotransmitter at the synapse. The transmitter travels and acts on a receptor in the next neuron's membrane.  The receptor's functional nature can excite, inhibit, or modify the neuron's sensitivity. About 30 different transmitter substances are reported. Chemical synapses transmit signals in one direction, from the presynaptic neuron to the post synaptic neuron. This unidirectional conduction aids in sensation, motor control, memory, and other functions. Electrical synapses are small protein-based channels connecting neurons, allowing electricity to flow between nerve cells. They are rare in the central nervous system and are used in smooth and cardiac muscles to transmit action potentials and signals in either direction. Synaptic Junctions in the Nervous System Axosomatic Synapse: Synapse between neuron's axon and soma. Found in spinal cord and autonomic ganglia. Axoaxonic Synapse: Synapse between axons in spinal cord. Between axons of interneurons. Axodentritics Synapse: Synapse between neuron's axon and dendrite. Present in dorsal horn of spinal cord. Dendrodentritic Synapse: Synapse between dendrites of different somas. Present in cerebellum. The neuromuscular junction (NMJ) is a well-understood chemical synapse between a motor neuron and a skeletal muscle cell. Motor neurons have their cell bodies in the CNS and their axons travel through peripheral nerves to the muscle. Each motor neuron synapses on multiple muscle fibers, but each muscle fiber is controlled by only one motor neuron. The neuromuscular junction (NMJ) consists of presynaptic elements, postsynaptic elements, and a synaptic cleft. Its presynaptic side is composed of synaptic boutons, which contain synaptic vesicles containing acetylcholine. The active zone, associated with each double row of vesicles, releases acetylcholine into the synaptic cleft. Mitochondria provide energy and local synthesis of acetylcholine. The synaptic cleft, which is about 50 nm wide contains extracellular fluid and a basal lamina, composed of a matrix of molecules that mediate synaptic adhesion between neuron and muscle. The postsynaptic muscle cell membrane contains acetylcholine receptors on junctional folds, increasing surface area for receptors. These folds are densely packed at the mouth, aligning with presynaptic terminals. The motor end plate of the neuromuscular junction contains these receptors. Activation of these receptors triggers muscle fiber contraction. Motor neurons' firing frequency is determined by the CNS. Action potential originates at the axon segment and travels to the presynaptic terminal. Na+ and K+ ions exchange across channels, while depolarization opens Ca2+ channels, allowing Ca2+ influx into the neuron and releasing neurotransmitters. Synaptic Vesicles and Ca2+ Release Acetylcholine-containing synaptic vesicles dock at active zones of presynaptic terminal. Soluble protein complex binds to vesicle and voltage-gated Ca2+ channels. Intertwining of binding proteins on vesicle and terminal membranes forms SNARE complex. SNARE complex holds vesicle close to terminal membrane and voltage-gated Ca2+ channels. Synaptotagmin, a calcium sensor molecule, is involved in this priming process. Vesicle and terminal membranes are drawn closer, forming synaptotagmin. Depolarization of terminal membrane opens voltage-gated Ca2+ channels, binds with synaptotagmin. Rapid fusion of vesicle and terminal membranes occurs, releasing ACh into synaptic cleft. Vesicle membrane is retrieved and recycled post-release, refilled with acetylcholine. Bacterial toxins can destroy SNARE binding proteins, affecting vesicle release.  Acetylcholine diffuses across synaptic cleft and binds with nicotinic acetylcholine receptors in postsynaptic muscle membrane. The nicotinic acetylcholine receptor is a ligand-gated ion channel with two binding sites. Acetylcholine binds at these sites, opening the channel and allowing Na+ ions to diffuse into the muscle cell. This leads to depolarization of the postsynaptic muscle cell membrane.  The neuromuscular junction produces an end-plate potential, opening voltage-gated Na+ channels to generate an action potential. Acetylcholine on nicotinic receptors is destroyed by acetylcholinesterase after binding for approximately 1ms. Acetylcholinesterase, anchored to the synaptic cleft, breaks down acetylcholine into acetate and choline molecules. Choline, a precursor of acetylcholine synthesis, is recycled in the presynaptic terminal. Chemicals inhibiting acetylcholinesterase can prolong acetylcholine at the synapse, leading to physiological consequences. Neuromuscular junction synaptic transmission differs from neuron-to-neuron synaptic transmission, which uses various neurotransmitters like NT and acetylcholine for postsynaptic effects. Release from terminals depends on Ca2+ influx. Atypical neurotransmitters, like endocannabinoids and nitric oxide, diffuse back across postsynaptic cells to affect presynaptic terminal function. The postsynaptic membrane in neuron-to-neuron synapses can be soma, dendrites, or terminals. Postsynaptic release at the neuromuscular junction produces excitation or inhibition. The postsynaptic receptor is mainly the nicotinic acetylcholine receptor. The Physiology of Muscle There are three types of muscle in the body: Skeletal, cardiac, and smooth muscle. Skeletal muscle, comprising 40% of the body, is crucial for understanding its function and control by the nervous system. It is also a key focus in veterinary patients with neuromuscular system diseases, as abnormalities in cardiac and smooth muscle are common in other disorders. Smooth muscle and cardiac muscle make up almost 10% of the body. Skeletal muscle, consisting of a central, fleshy, contractile muscle belly and two tendons, is arranged in the body to originate and insert bones in a joint. When activated by a motor nerve, it can only shorten, causing bones to bend at the joint. Skeletal Muscle Structures Skeletal muscles have multiple levels of organization, with each muscle belly consisting of muscle fibers spanning from the origin to its insertion point. These fibers contain multiple nuclei, mitochondria, and intracellular organelles. The outer limiting is called the sarcolemma, and each fiber is innervated by one motor neuron. Myofibrils, smaller subunits, are arranged parallel along the fiber's length and consist of repeating sarcomeres, the basic contractile units of the muscle fiber. The sarcomere, a muscular muscle cell, contains a Z disk at each end and numerous actin filaments. These filaments consist of two intertwined helical strands of actin and tropomyosin protein, wound together. Troponin, a complex globular protein, binds tropomyosin and actin and has an affinity for calcium ions. Myosin protein polymers are suspended between and parallel to the actin filaments. A myosin molecule is composed of a tail made of intertwined helices and two globular heads that bind to ATP and actin. Around 500 myosin heads on a thick filament form cross-bridges with actin, facilitating the shortening of the sarcomere through the flexing and relaxing of these myosin heads.. Titin, a spring-like protein in the sarcomere, attaches to myosin and Z disks, maintains the side-by-side relationship of actin and myosin, elasticity, and resting length of the sarcomere. Sarcoplasmic Reticulum in Muscle An intracellular storage organelle beneath the plasma membrane. Forms a network around myofibrils, sequestering Ca2+ ions in relaxed muscle. Similar to smooth endoplasmic reticulum in other cells. Transverse Tubules (T tubules) Periodic invaginations of the sarcolemma. Perpendicular to the long axis of the muscle fiber. Snake between myofibrils, forming junctions with the sarcoplasmic reticulum network. Fills with extracellular fluid, allowing depolarization of action potential to the muscle fiber's interior. Excitation-Contraction Coupling Muscle cells and neurons have resting membrane potentials. Muscle cell membrane can be depolarized via synaptic transmission at the neuromuscular junction. Acetylcholine from the motor neuron activates nicotinic acetylcholine receptors in the muscle cell's motor end-plate region. This depolarization, termed an end-plate potential (EPP), is similar to an EPSP in a neuron. Action potential from the neuromuscular junction spreads along the muscle fiber and interior, reaching the sarcoplasmic reticulum and innermost muscle fiber regions. Rise in cytoplasmic Ca2+ at the neuron terminal initiates transmitter release. Ca2+ ions in muscle cell sarcoplasm initiate contraction. At rest, Ca2+ ions are pumped out and stored in the sarcoplasmic reticulum. Action potential spreads along muscle fiber surface and core, depolarizing the sarcoplasmic reticulum. Action potential arrival leads to release of stored Ca2+ ions, triggering contraction. Ca2+ ions diffuse into sarcoplasm, bathe myofibril sarcomeres, and trigger contraction. As action potential passes, Ca2+ is pumped back into the sarcoplasmic reticulum, resulting in relaxation. Depolarization leads to configurational change in voltage-gated Ca2+ channel aggregates. Mechanical coupling on SR membrane opens Ca2+ release channels. Ca2+ released from SR into sarcoplasm induces contraction in sarcomeres. Dihydropyridine (DHP) receptors or ryanodine receptors link action potential and Ca2+ release.  Mechanical coupling with DHP receptor subunits opens voltage-gated Ca2+ channels. Direct configurational change in DHP receptors on sarcoplasmic reticulum allows stored Ca2+ ions to escape. Actin Myosin Interaction Sarcomere shifts from relaxed to contracted state when Ca2+ ions are available. Actin filaments pull myosin filaments parallel, shortening sarcomere. Physical shortening of muscle end distance. In muscle, the interaction of myosin, ATP, and actin produces contraction and force. Step A: ATP binds to a myosin head, limiting myosin's ability to bind to actin. Step B: Enzymatic activity associated with the myosin head, ATPase, hydrolyzes ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi), which remain bound to myosin. Step C: Cross-bridging, a forceful flexing of the myosin head, causes the actin filament to slide past the thick filament, causing muscle contraction. This allosteric change alters myosin-binding properties, releasing ADP and Pi. Step D in Myosin Cycle New ATP molecule binding to myosin head. Myosin head unflexes, loses actin affinity. Releases cross-bridge, cycle restarts. Rigor mortis in animals is caused by lack of new ATP binding to myosin heads. Myosin heads remain in Step C without ATP. New ATP binding changes myosin shape, releasing the cross-bridge. Cycle can start over. Skeletal Muscle Classification: Fast Vs. Slow Fibers Fast-twitch fibers: Skeletal muscle fibers with rapid contraction speeds, thicker, extensive sarcoplasmic reticulum, and less extensive blood and mitochondrial supplies. Also known as white muscle.  Slow-twitch fibers: Skeletal muscle fibers with slower contraction speeds, thinner, rich blood and mitochondrial supply, and large myoglobin content. A third type, a subclass of fast-twitch fibers, varies in proportions based on muscle use. The Motor Unit Defined as one alpha (α) motor neuron and all extrafusal muscle fibers it innervates. All muscle fibers are of the same functional type. An action potential on the motor neuron causes simultaneous contraction of all muscle fibers. Each motor neuron's axon branches, innervating several muscle fibers. Neuronal cell bodies of motor units form a cluster in the central nervous system. Motor unit sizes range within the pool. Muscles with smaller motor units have better control over contractile force. The CNS can instruct a muscle to contract with greater force through two processes: multiple-fiber summation and frequency summation. Multiple-fiber summation involves increasing the number of motor units that contract simultaneously, starting with smaller units and increasing force gradually. Frequency summation involves increasing the frequency of motor unit activation, causing subsequent contractions to begin before relaxation. This results in smooth, continuous muscle contraction, called complete tetany, when stimulation frequency is high. The Cardiac Muscle Characteristics: Strained, contains sarcoplasmic reticulum, myofibrils, and a fundamental contractile component. Features include interconnected gap junctions that bridge intercalated disks. Gap junctions provide cytoplasmic continuity and electrical coupling, allowing action potentials to spread across intercalated disks. This allows the heart to act as a functional syncytium, with large regions of the heart muscle contracting simultaneously. Ca2+-Induced Ca2+ Release in Cardiac Muscle: Action potential along cell membrane and T tubules opens voltage-gated Ca2+ channels. Extracellular Ca2+ ions influx into cytoplasm activates Ca2+ release channels on sarcoplasmic reticulum. Increased cytoplasmic Ca2+ triggers contraction. Muscle relaxation pumps cytoplasmic Ca2+ back into sarcoplasmic reticulum, with some transported across sarcolemma. The Smooth Muscle Smaller and shorter than skeletal muscle cells. Lack T tubules and poorly developed sarcoplasmic reticulum. Induce contraction through Ca2+ ions from extracellular fluid. Contractile units form overlapping actin and myosin molecules. Lacks structural regularity causing striated appearance. Actin filaments anchored to dense bodies in cytoplasm and cell membrane. Visceral or unitary smooth muscle: Operates like a functional syncytium, with cell-to-cell action potential transmission and coordinated contraction. Abundant in the gastrointestinal tract and thoracic and abdominal cavities. Multiunit smooth muscle: Electrically isolated muscle cells capable of independent contraction. Found in the iris and ciliary body of the eye for precise control of muscular contraction. Smooth muscle tissue, innervated by autonomic nervous system neurons, can contract through acetylcholine or norepinephrine binding. It can be excited or inhibited by presynaptic input. Different types of muscle tissue contract in response to electrical activity, hormonal action, or stretch, with multilayer visceral and multiunit types. Smooth muscle cells lack a well-developed sarcoplasmic reticulum, relying on extracellular Ca2+ influx for contractile processes. This is achieved through voltage-gated channels in caveolae, and terminated by slow Ca2+ transport. Upper & Lower Motor Neurons Lower Motor Neuron (LMN) LMN is a neuron with cell bodies in the central nervous system and peripheral nerves. It consists of alpha (α) motor neurons responsible for muscle contraction, gamma (γ) motor neurons innervating muscle spindles, and pre- and postganglionic autonomic neurons. Damage to the Lower Motor Neuron (LMN): Clinical Signs and Effects Paralysis or paresis: Damage to α motor neurons prevents action potentials from reaching the neuromuscular junction. Flaccid paralysis: No muscle contraction occurs. Paresis: Incomplete paralysis due to nerve damage or presence of other nerves. Atrophy: Shrinkage or wasting of skeletal muscle mass distal to the lower motor neuron lesion. Reduced muscle stimulation triggers reductions in muscle protein synthesis and increases in muscle proteolysis. Activation of ubiquitin-proteasome and autophagy-lysosome proteolytic pathways is underlying this muscle breakdown. Loss of Segmental and Intersegmental Reflexes Reflexes require a viable α motor neuron in the reflex arc. Muscle stretch, toe-pinch withdrawal, and proprioceptive positioning reactions fail due to motor neuron loss. Abnormal electrical activity of the muscle can be observed on an electromyogram within days of α motor neuron damage. Upper Motor Neuron (UMN) Cell body, dendrites, and axon located in CNS. Originators of corticospinal, corticobulbar, and descending brainstem motor pathways. Send axons to control lower motor neurons. Initiate voluntary movement by cortical origin upper motor neurons. UMN Damage and Clinical Signs UMN lesions can cause movement disorders. Spinal cord disease affects UMN projecting to the cord, causing weakness below the lesion. Brain disease affects UMN, causing rigidity, seizures, circling gaits, and inappropriate movements. Muscle doesn't typically atrophy due to intact lower motor neuron. Modest disuse atrophy may develop later. Upper Motor Neuron Disease and Segmental Reflexes Neuronal circuitry of segmental reflex arc retained in upper motor neuron disease. Damage to upper motor neurons can decrease inhibition, leading to hyperreflexia. Muscle electrical activity appears normal due to intact lower motor neurons.