Organization of the Nervous System PDF

- ORGANIZATION OF THE NERVOUS SYSTEM - Neurons - **Neuronal Composition** - The central nervous system (CNS) contains approximately 80 to 100 billion neurons - A typical neuron receives signals through **synapses** on the **dendrites and soma** and sends output...

- ORGANIZATION OF THE NERVOUS SYSTEM - Neurons - **Neuronal Composition** - The central nervous system (CNS) contains approximately 80 to 100 billion neurons - A typical neuron receives signals through **synapses** on the **dendrites and soma** and sends output signals via a **single axon** - **Signal Flow** - Signals pass in a **one-way direction** across synapses, from the **axon** of one neuron to the **dendrites** of the subsequent neuron - **Transmission of Information** - Information is carried as **nerve impulses** (action potentials) through sequential neurons - These impulses can be: - **Blocked** between neurons - **Transformed** into repetitive impulses - **Integrated** with other impulses for complex patterns - Synapses - **Synapse**: Junction between neurons, allows signal transfer and controls **direction** of signal flow - **Ease of Transmission**: Some synapses transmit signals readily, while others offer resistance - **Regulation by External Signals**: - **Facilitatory signals** can enhance transmission - **Inhibitory signals** can reduce or block transmission - **Physiologic Anatomy of the Neuron** - **Key Components of the Neuron**: - **Soma**: Cell body of the neuron - **Axon**: Extends from soma to subsequent nerves, carrying output signals - **Dendrites**: Branch out from the soma with up to 200,000 presynaptic terminals - **Synaptic Transmission**: - **Presynaptic Terminals**: Form synapses with other neurons - Can be **excitatory** (stimulating) or **inhibitory** (blocking) - **Calcium Channels & Neurotransmitter Release**: - Depolarization opens voltage-gated calcium channels - Calcium influx triggers neurotransmitter release from vesicles - **Effect on Neurotransmitter on Postsynaptic Terminals**: - **Ionotropic Receptors**: Directly open ion channels - **Metabotropic Receptors**: Activate second messengers to alter cell functions - **Transmitter Actions** - **Types of Ion Channels**: - **Cation Channels**: Allow sodium (Na+), sometimes potassium (K+) or calcium (Ca2+) influx; **excitatory** - **Anion Channels**: Primarily allow chloride (Cl-) ions influx; **inhibitory** - **Channel Selectivity**: Determined by size, shape, and charge of the channel - **Second Messenger Systems**: - **G Proteins**: - **Activation Process**: G protein binds GTP, separates into active components - **Functions**: - Open ion channels for prolonged effects - Activate **cAMP** or **cGMP** to alter cell activity - Activate enzymes for specific cellular functions - Trigger **gene transcription**, leading to long-term changes - **Excitation and Inhibition** - **Mechanisms of Excitation**: - **Opening Sodium Channels**: Allows positive ions to enter, increasing membrane potential toward threshold - **Reduced Chloride or Potassium Conductance**: - **Chloride**: Less negative ions enter - **Potassium**: Fewer positive ions leave - Both actions make the inside of the cell more positive - **Metabolic Changes**: - Increase excitatory receptors or decrease inhibitory receptors on the membrane - **Mechanisms of Inhibition**: - **Opening Chloride Channels**: Negative ions flow in, making the cell interior more negative - **Increased Potassium Conductance**: Positive ions exit, further increasing negativity inside - **Enzyme Activation**: Alters cellular functions to boost inhibition and reduce excitation - **Types of Synapses** - **Chemical Synapses**: - Predominant in the brain and CNS - **Mechanism**: Presynaptic neuron releases neurotransmitters to excite, inhibit, or modify the postsynaptic neuron - **One-Way Conduction**: Signals move in a single direction, supporting targeted actions like sensation and motor control - **Examples of Neurotransmitters**: Acetylcholine, norepinephrine, GABA, serotonin, glutamate - **Electrical Synapses**: - Cytoplasms of adjacent cells connected by **gap junctions** - **Mechanism**: Gap junctions allow free movement of ions and, therefore, electrical charge - **Bidirectional Transmission**: Allows coordinated activity across interconnected neuron groups - Common in **cardiac** and **smooth muscle** - **Synaptic Transmitters** - **Small-Molecule, Rapidly Acting Transmitters**: - Trigger **acute responses** like sensory and motor signals - Synthesized in the **cytosol of presynaptic terminals** and stored in **recycled vesicles** - Example: **Acetylcholine**---synthesized from acetyl CoA and choline, broken down by cholinesterase in the synaptic cleft - **Neuropeptides, Slowly Acting Transmitters**: - Induce **prolonged effects** (e.g., receptor number changes, long-term synapse modifications) - Synthesized in the **cell body** and transported to nerve terminals - Released vesicles are **not recycled**; neuropeptides are more potent but released in smaller quantities - **Co-Transmission**: - Some neurons store both types in the same or separate vesicles, releasing them simultaneously or in sequence - **Resting Membrane Potential** - **Resting Membrane Potential**: - \~ -65 mV in neurons - **Ion Concentrations**: - High **Na+** outside, low inside - High **K+** inside, low outside - **Cl-** high outside, low inside due to the negative membrane potential - **Neuronal Excitation** - **Excitatory Postsynaptic Potential (EPSP)**: - **Na+ Influx** raises membrane potential (e.g., -65 mV to -45 mV) - Threshold for action potential \~ -45 mV - Initiates at the **axon hillock**, where voltage-gated Na+ channels are dense - **Summation**: - **Spatial Summation**: Multiple presynaptic terminals fire simultaneously - **Temporal Summation**: Repeated firing of one terminal over time - **Dendritic Transmission**: - Primarily by **electronic conduction**; no action potentials - Closer synapses to soma have a greater effect - **Neuronal Inhibition** - **Presynaptic Inhibition**: - Inhibitory transmitter (often **GABA**) acts on presynaptic terminals - GABA opens Cl- channels in the terminal, reducing the excitatory effect by counteracting Na+ influx - **Inhibitory Postsynaptic Potential (IPSP)**: - **Chloride Channels**: Open to allow Cl- influx, making the interior more negative - **Potassium Channels**: Open for K+ efflux, also increasing intracellular negativity - **Summation of IPSP and EPSP**: - IPSPs counteract EPSPs; they can partially or fully cancel each other - If excitatory potential nears but doesn't reach threshold, the neuron is **facilitated**, making it more responsive to future excitatory inputs - **Hyperpolarization**, moving membrane potential further from threshold (e.g., towards -70 mV) - **Special Characteristics of Synaptic Transmission** - Sensation - **Initiation of Nervous System Activities**: - Most activities are triggered by **sensory experiences** - Sensory input can lead to **immediate responses** or be **stored as memories** for future reactions - **Sensory Information Pathway**: - Sensory data from receptors is transmitted through **peripheral nerves** to the CNS - Information is relayed to multiple areas: - **Spinal Cord**: Initial processing and reflexes - **Reticular Substance**: Located in the medulla, pons, and midbrain - **Cerebellum**: Coordinates fine motor control - **Thalamus**: Acts as a sensory relay station - **Cerebral Cortex**: Integrates sensory information for perception and decision-making - Motor Function - **Primary Role of the Nervous System**: - Controls bodily functions by regulating: - **Skeletal Muscle Contraction**: Enables movement - **Smooth Muscle Contraction**: Manages internal organ function - **Secretion of Substances**: Activates exocrine and endocrine glands - **Effectors**: - Muscles and glands are the **effectors**, carrying out responses based on nerve signals - **Levels of Control for Skeletal Muscles**: - **Spinal Cord**: Manages reflexive, automatic responses - **Reticular Substance**: Controls arousal and involuntary motor functions - **Basal Ganglia**: Facilitates smooth voluntary movements - **Cerebellum**: Refines coordination and balance - **Motor Cortex**: Plans and initiates complex voluntary movements - **Major Divisions of Central Nervous System** - **Spinal Cord Level** - Functions independently for many reflexes and movements - Examples: - **Walking movements** - **Withdrawal reflexes** (from painful stimuli) - **Postural reflexes** (supporting body against gravity) - **Autonomic reflexes** (control of blood vessels, digestion, and excretion) - **Lower Brain (Subcortical) Level** - Manages subconscious and autonomic functions - Includes medulla, pons, mesencephalon, hypothalamus, thalamus, cerebellum, and basal ganglia - Controls **emotional responses** (e.g., anger, pleasure) and **basic life functions** - **Higher Brain (Cortical) Level** - Acts as a large **memory storehouse** - Essential for **thought processes** and precise control over lower brain functions - Works in **association** with lower centers, which initiate wakefulness and access to memories - **Integrative Function of the Nervous System** - **Information Processing**: - One of the primary functions of the nervous system is to process sensory input to elicit appropriate mental and motor responses - **Filtering of Sensory Input**: Over 99% of sensory information is discarded as irrelevant or unimportant - **Channeling Important Information**: - Significant sensory inputs are directed to specific **integrative and motor regions** of the brain - This selective channeling is essential for focusing the brain\'s responses on meaningful stimuli - **Integrative Function**: - The process of filtering, channeling, and directing sensory information to evoke targeted responses is known as the **integrative function** - **Storage of Information** - **Memory and Information Storage**: - Most sensory information is stored for future use, primarily in the **cerebral cortex** - Storage of information forms the basis of **memory** - **Synaptic Facilitation**: - **Repeated Signal Transmission** strengthens synapses, making them more capable of transmitting similar signals in the future - This process, called **facilitation**, enables memories to be recalled even without sensory input - **Role in Thinking**: - Stored memories become part of the brain\'s **processing mechanism** - New sensory experiences are compared to existing memories, helping filter and prioritize new information - SENSORY RECEPTORS AND NEURONAL CIRCUITS - **Types of Sensory Receptors** - **Mechanoreceptors**: - Detect **mechanical compression** or **stretching** in tissues - **Thermoreceptors**: - Sense **temperature changes**, with distinct receptors for cold and warmth - **Nociceptors** (Pain Receptors): - Detect **physical or chemical damage** in tissues - **Electromagnetic Receptors**: - Respond to **light on the retina**, enabling vision - **Chemoreceptors**: - Detect **chemical changes**: - Taste (mouth) - Smell (nose) - Oxygen and carbon dioxide levels (blood) - Osmolality and other chemical factors in body fluids - **Differential Sensitivity** - **Receptor Potentials** - **Adaptation of Receptors** - **Nerve Fibers** - **Need for Speed in Signal Transmission**: - Rapid transmission required for certain information (e.g., touch, motor control) - Slower transmission sufficient for prolonged sensations like aching pain - **General Classification**: - **Type A Fibers**: Large to medium myelinated fibers with high conduction velocity - Subtypes: **Aα, Aβ, Aγ, Aδ** - **Type C Fibers**: Small, unmyelinated fibers with low conduction velocity - Constitute most sensory fibers in peripheral nerves and all postganglionic autonomic fibers - **Function and Conduction Velocity**: - **Type A Fibers**: Fast conduction for functions requiring quick response (e.g., motor control) - **Type C Fibers**: Slower conduction, used for signals that can tolerate delay (e.g., chronic pain) - Summation - **Importance of Signal Intensity**: - Signal intensity must be conveyed accurately to reflect the strength of stimuli - **Mechanisms for Transmitting Intensity**: - **Spatial Summation**: - Involves activating **increasing numbers of parallel fibers** - Stronger signals recruit additional fibers, broadening the response area - Example: Pain fibers covering a large area of skin, with each fiber branching into many nerve endings - **Temporal Summation**: - Increases the **frequency of action potentials** within a single fiber - Higher stimulus intensity results in more frequent impulses along the same fiber - Neuronal Pools - **Neuronal Pools**: - Composed of varying numbers of neurons, each pool processes signals uniquely - **Stimulatory Field**: The area within a pool influenced by an incoming fiber, with the strongest influence on nearby neurons - **Divergence**: - **Amplifying Divergence**: Signal spreads to an increasing number of neurons in successive orders (e.g., corticospinal pathway) - **Divergence into Multiple Tracts**: Signal splits and travels to different areas (e.g., dorsal columns to cerebellum and thalamus) - **Convergence**: - **Single Source Convergence**: Multiple terminals from a single input fiber unite on one neuron, enabling spatial summation - **Multiple Source Convergence**: Inputs from multiple sources (e.g., peripheral nerves, corticospinal tract) combine on a single neuron, allowing summation of diverse signals - **Stimulation and Inhibition** - **Action Potential Requirements**: - A single excitatory input rarely causes an action potential - **Summation of inputs** (either simultaneously or in rapid succession) is needed to excite the neuron - **Zones within a Neuronal Pool**: - **Discharge Zone** (Excited/Liminal Zone): Neurons are strongly stimulated and reach threshold for activation - **Facilitated Zone** (Subthreshold/Subliminal Zone): Neurons are influenced but do not reach threshold; they are more excitable for future signals - **Inhibitory Zone**: Inhibitory input dampens neuron activity, with the strongest inhibition at the center of the field - **Reciprocal Inhibition Circuit**: - Enables coordination of antagonistic muscle pairs - Input fiber excites one pathway and activates an **inhibitory interneuron** to inhibit the opposing pathway - Afterdischarge - **Afterdischarge**: - A prolonged output discharge from a neuron that continues **after the initial signal** ends - Duration ranges from milliseconds to several minutes, depending on the mechanism - **Mechanism of Afterdischarge**: - **Postsynaptic Potential**: Excitatory synapses create an electrical potential that can persist for milliseconds, especially with long-acting neurotransmitters - Sustained potential causes the neuron to continue firing a **train of impulses**, even after the initial input signal has ceased - **Significance**: - Allows a single brief input to produce a prolonged effect, enabling sustained output without continuous input - Important for processes requiring extended responses, such as maintaining muscle tone or continuous signal output - Continuous and Rhythmical Output in Neuronal Circuits - **Continuous Output**: - **Intrinsic Neuronal Discharge**: - Some neurons have a high enough **membrane potential** to emit impulses continuously - Common in neurons of the **cerebellum**; output rate can be adjusted by excitatory or inhibitory inputs - **Reverberatory Circuits**: - Self-sustaining **reverberating circuits** generate continuous impulses - Input signals can increase or decrease the output; inhibition can extinguish the signal - **Rhythmical Output**: - **Rhythmical Signals**: Produced by reverberating circuits that create cyclical patterns - Examples: **Respiratory rhythm** (medulla and pons), heart rate, vascular tone, and digestive activity - **Stabilization Mechanisms in the Nervous System** - **Inhibitory Circuits**: - **Inhibitory Feedback Circuits**: - Feedback from pathway termini inhibits excitatory neurons at the input or intermediate stages. - Common in sensory pathways to prevent overexcitation - **Inhibitory Neuronal Pools**: - Certain pools, like the **basal ganglia**, exert broad inhibitory control, stabilizing functions such as muscle control - **Synaptic Fatigue**: - **Progressive Weakening**: Synaptic transmission decreases with prolonged excitation - Moderates the sensitivity of overused pathways (fatigue) and increases sensitivity in underused pathways (recovery) - **Long-term Regulation**: - **Downregulation** of receptors with overactivity - **Upregulation** of receptors with underactivity - SOMATIC SENSATIONS - Classification of Somatic Senses - **Physiological Types of Somatic Senses**: - **Mechanoreceptive Senses**: - Includes **tactile** and **position** senses - Activated by mechanical displacement in body tissues - **Thermoreceptive Senses**: - Detects **heat** and **cold** - **Pain Sense**: - Triggered by factors that cause **tissue damage** - **Other Classifications**: - **Exteroreceptive Sensations**: From the body surface - **Proprioceptive Sensations**: Related to body's physical state (e.g., position, muscle tension, balance) - **Visceral Sensations**: Arising from internal organs (viscera) - **Deep Sensations**: From deep tissues, including fasciae, muscles, and bones; includes deep pressure, pain, and vibration - Tactile Receptors - **Touch, Pressure, and Vibration**: - **Touch**: Detected by tactile receptors near the skin surface - **Pressure**: Result of deformation in deeper tissues - **Vibration**: Detected through rapidly repetitive signals - **Types of Tactile Receptors**: - **Free Nerve Endings**: Found throughout skin; detect touch and pressure - **Meissner's Corpuscles**: Highly sensitive, rapid-adapting; abundant in fingertips and lips - **Merkel's Discs**: Slow-adapting, grouped in touch domes; localize touch and texture - **Hair End-Organs**: Detect movement and initial contact; adapt quickly - **Ruffini's Endings**: Slow-adapting; detect continuous deformation, found in skin and joint capsules - **Pacinian Corpuscles**: Rapid-adapting; detect vibration and quick changes in pressure - **Nerve Fiber Types**: - **Type Aβ**: Rapid transmission (30-70 m/s), used by most specialized receptors - **Type Aδ and Type C**: Slower transmission for free nerve endings; carry less critical signals - **Detection of Vibration, Tickle, and Itch** - Position Senses (Proprioception) - **Types of Position Senses**: - **Static Position Sense**: - Conscious perception of body orientation and position of body parts relative to each other - **Dynamic Position Sense** (Kinesthesia): - Awareness of the speed and direction of movement - **Mechanisms of Position Sensing**: - **Joint Angulation**: Determined by multiple receptors that provide information on the angle and movement of joints - **Receptor Types**: - **Muscle Spindles**: Key for sensing midrange joint angles and changes in muscle stretch - **Deep Receptors (e.g., Pacinian Corpuscles, Ruffini's Endings)**: Important at extreme joint angles, detect stretch in ligaments and deep tissues - **Golgi Tendon-Like Receptors**: Provide information on muscle tendon tension - Somatosensory Cortex - **Cerebral Cortex Layers**: - **Six Layers of Neurons**: - **Layer IV**: Primary entry point for sensory signals - **Layers I & II**: Receive diffuse input for excitability control - **Layers II & III**: Send signals across hemispheres via the corpus callosum - **Layers V & VI**: Project to deeper brain areas, controlling signal transmission and influencing thalamic activity - **Vertical Columns**: - Each column specializes in a single sensory modality (e.g., touch, pressure) - Located in **somatosensory area I** (postcentral gyrus), organized by body region - **Somatosensory Areas**: - **Somatosensory Area I**: - High degree of localization; different parts of the body are represented proportionally to receptor density (e.g., large areas for lips, fingertips) - Key for precise tactile information (located in Brodmann's areas 3, 1, and 2) - **Somatosensory Area II**: - Less precise localization - Somatosensory Association Areas - **Location**: - **Brodmann's Areas 5 and 7** in the parietal cortex, located behind somatosensory area I - **Function**: - Combines and interprets sensory information from **somatosensory area I** - Deciphers the deeper meanings of sensory input by integrating information from multiple sensory points - **Effects of Damage**: - **Amorphosynthesis**: - Loss of ability to recognize complex objects or forms by touch on the opposite side of the body - Reduced awareness of the opposite side of the body and body parts - Leads to a lack of spatial and form perception on the affected side - **Dermatomes** - **Dermatome Definition**: - Each spinal nerve innervates a specific area of skin known as a **dermatome** - A dermatome represents the **segmental field** of skin supplied by a single spinal nerve - **Overlap of Dermatomes**: - Adjacent dermatomes overlap significantly - While dermatomes are depicted with clear borders, boundaries are not sharply defined in reality - **Clinical Relevance**: - Understanding dermatomes is essential for diagnosing nerve damage or sensory loss - Patterns of sensory changes can help localize spinal nerve or spinal cord issues - **Sensory Pathways to the Brain** - **Sensory Information Entry**: - Sensory signals enter the **spinal cord** through the **dorsal roots** of spinal nerves - **Two Main Sensory Pathways**: - **Dorsal Column-Medial Lemniscal System**: - High **spatial orientation** of nerve fibers - Transmits information **rapidly** with high **temporal and spatial fidelity** - Ideal for precise, localized sensations - **Anterolateral System**: - Less spatial orientation - Transmits information that does not require high speed or precision - Suitable for generalized sensations - **Functional Differences**: - **Dorsal Column**: For sensory information that needs rapid, accurate transmission - **Anterolateral System**: For sensory signals that can tolerate slower, less precise transmission - **Dorsal Column-Medial Lemniscal System** - **Initial Division**: - Large myelinated fibers divide into **medial** and **lateral branches** upon entering the spinal cord - **Medial Branch**: Travels upward through the **dorsal columns** to the brain - **Lateral Branch**: Synapses locally in the dorsal horn and serves three functions: - Sends fibers to the **dorsal columns** for upward travel - Terminates locally to mediate **spinal reflexes** - Contributes to the **spinocerebellar tracts** - **Path to the Brain**: - Fibers ascend through the **dorsal columns** to the **dorsal medulla** and synapse in the **cuneate and gracile nuclei** - Second-order neurons cross to the opposite side in the medulla and ascend via the **medial lemnisci** to the **thalamus** - **Thalamic Relay and Cerebral Cortex Projection**: - In the **thalamus**, fibers terminate in the **ventrobasal complex** - Third-order neurons project to **somatosensory area I** in the **postcentral gyrus** - **Spatial Orientation**: - Maintained throughout the pathway, with lower body fibers central and higher body fibers more lateral in the dorsal columns - Medial lemniscal crossing results in **contralateral representation** in the thalamus - **Signal Transmission and Analysis in the Dorsal Column Pathway** - **Neuronal Circuit Organization**: - **Divergence** at each synaptic stage; stronger stimuli activate more neurons, especially in the central cortical field - **Two-Point Discrimination**: - Tested by the **two-point discrimination** method - Fine discrimination: **1-2 mm** on fingertips - Poorer discrimination: **30-70 mm** on the back, due to fewer tactile receptors - **Lateral Inhibition**: - **Enhances contrast** by blocking lateral spread of excitatory signals - Occurs at multiple levels: dorsal column nuclei, thalamus, and cortex - **Vibratory Signal Transmission**: - High-frequency vibrations (up to **700 cycles/sec**) detected by **Pacinian corpuscles** - Lower frequencies (below **200 cycles/sec**) detected by **Meissner's corpuscles** - Important test for dorsal column integrity in neurological exams - **Intensity Transmission**: - **Intensity encoded by**: - Increased **number of activated fibers** - Higher **impulse rate in each fiber** - Enables sensory systems to handle a wide range of stimulus intensities - **Anterolateral System** - Pain - Fast and Slow Pain - **Fast Pain**: - Felt within **0.1 seconds** of stimulus - Alternative names: **Sharp pain, pricking pain, acute pain, electric pain** - Common stimuli: **Needle prick, skin cut, acute burn** - Limited to **superficial tissues**; rarely felt in deep tissues - **Slow Pain**: - Begins **1 second or more** after stimulus, increasing gradually - Alternative names: **Burning pain, aching pain, throbbing pain, chronic pain** - Associated with **tissue destruction**; can lead to prolonged suffering - Occurs in both **superficial tissues** and **deep tissues/organs** - **Referred Pain** - **Definition**: - **Referred Pain**: Pain perceived in a location distant from the actual source of pain, often in a superficial area while the source is deep or visceral - **Clinical Importance**: - Vital in diagnosing **visceral ailments** where referred pain may be the only symptom - **Mechanism**: - **Shared Pathways**: Visceral pain fibers synapse on the same **second-order neurons** in the spinal cord that receive pain signals from the skin - **Perceived Origin**: Pain from internal organs is \"referred\" to the skin because **both signals share common neurons**, leading the brain to perceive the sensation as originating from the skin - Visceral Pain - **Challenges in Localizing Visceral Pain**: - **Lack of direct experience** with internal organs leads to poor localization - **Dual pain pathways** from visceral organs complicate localization - **Dual Pathways**: - **True Visceral Pathway**: - Pain signals travel via **autonomic nerves** - Referred to surface areas far from the origin, based on **embryonic origin** (e.g., appendix pain referred to the umbilical area) - **Parietal Pathway**: - Pain signals from **parietal peritoneum, pleura, or pericardium** travel via **local spinal nerves** - Pain localized directly over the affected area - **Dual Transmission Example**: - **Appendix Pain**: - **Visceral Pain**: Referred to the **umbilical region** (T10-T11) as aching/cramping - **Parietal Pain**: Sharp pain over the **right lower quadrant**, where the inflamed appendix contacts the peritoneum - **Characteristics and Causes of Visceral Pain** - **Diagnostic Importance**: - Visceral pain is often the only indicator of **visceral inflammation, infection, or disease** - **Key Differences from Surface Pain**: - **Localized damage** to viscera typically does not cause severe pain (e.g., gut incision) - **Diffuse stimulation** of pain fibers, such as from ischemia, causes intense pain - **Causes of Visceral Pain**: - **Ischemia**: Reduced blood supply leads to accumulation of acidic metabolic products - **Chemical Damage**: Leakage of substances (e.g., gastric juice) causing severe peritoneal pain - **Spasm of Smooth Muscle**: Causes intermittent, cramping pain (e.g., in appendicitis, gallbladder disease) - **Overdistention**: Overfilling of hollow organs may stretch tissues and collapse blood vessels, leading to pain - **Pain-Sensitive vs. Insensitive Areas**: - **Insensitive Areas**: Liver parenchyma, lung alveoli - **Sensitive Areas**: Liver capsule, bile ducts, bronchi, and parietal pleura - Parietal Pain - **Parietal Surfaces**: - Include **parietal peritoneum, pleura,** and **pericardium** - Supplied with **extensive pain innervation** similar to the skin - **Sharp Pain in Visceral Disease**: - When disease affects a **viscus** and spreads to the parietal surfaces, pain is felt more sharply - Parietal pain is often **well-localized** over the affected area, unlike diffuse visceral pain - **Fast-Sharp and Slow-Chronic Pain Pathways** - **Types of Pain and Stimuli**: - **Fast-Sharp Pain**: - Elicited by **mechanical or thermal stimuli** - Transmitted via **type Aδ fibers** at **6-30 m/sec** - **Slow-Chronic Pain**: - Primarily elicited by **chemical stimuli** (sometimes mechanical/thermal) - Transmitted via **type C fibers** at **0.5-2 m/sec** - **Double Pain Sensation**: - **Immediate fast-sharp pain** via Aδ fibers prompts quick reaction - **Delayed slow pain** via C fibers grows over time, reinforcing need for relief - **Pain Signal Processing in the Spinal Cord**: - **Entry**: Pain fibers enter the **spinal cord** via **dorsal spinal roots** - **Dual Processing Systems**: - Fast-sharp and slow-chronic pain signals are processed separately, with relay neurons in the **dorsal horns** - **Dual Pathways for Transmission of Pain Signals** - **Two Pathways for Pain Transmission**: - **Neospinothalamic Tract**: - Transmits **fast-sharp pain** signals - **Paleospinothalamic Tract**: - Transmits **slow-chronic pain** signals - **Brain Processing and Arousal**: - **Slow pain signals** terminate in the **reticular areas of the brain stem** and **intralaminar nuclei of the thalamus** - Strong arousal effect, **keeping the brain alert** -- explains difficulty sleeping during severe pain - **Role of Cerebral Cortex**: - Complete removal of somatic sensory cortex does not eliminate pain perception - **Lower brain centers** (brain stem and thalamus) are essential for conscious pain perception - The cortex helps in **interpreting pain quality** - **Clinical Intervention**: - **Cordotomy**: Cutting pain-conducting tracts (anterolateral quadrant) in the spinal cord to relieve intractable pain, typically for **lower body pain** - **Neospinothalamic Tract** - **Paleospinothalamic Tract** - **Pain Suppression (Analgesia) System** - **Analgesia System Components**: - **Periaqueductal gray** and **periventricular areas** in the mesencephalon and pons - **Raphe magnus nucleus** and **nucleus reticularis paragigantocellularis** in the medulla - **Dorsal horn inhibitory complex** in the spinal cord - **Pain Inhibition Pathway**: - Signals from **periaqueductal gray** → **raphe magnus nucleus** → **dorsal horns of spinal cord** - Serotonin release in the spinal cord stimulates **enkephalin** secretion, inhibiting pain signals - **Neurotransmitters and Natural Opiates**: - **Enkephalin and Serotonin**: Key neurotransmitters for pain suppression - Natural opiate-like substances: **β-endorphin, met-enkephalin, leu-enkephalin,** and **dynorphin** - **Clinical and Practical Applications**: - **Peripheral Tactile Stimulation**: Rubbing skin near painful areas activates **Aβ fibers**, providing pain relief through lateral inhibition - **Electrical Stimulation Techniques**: Electrodes on the skin, spinal cord, or brain regions (e.g., thalamus, periventricular, periaqueductal areas) for pain control - Thermal Sensations - **Thermal Sensations**: - Gradations: **Freezing cold, cold, cool, indifferent, warm, hot, burning hot** - Extreme temperatures can stimulate **pain receptors**, creating sensations of **freezing cold** or **burning hot** - **Types of Thermal Receptors**: - **Cold Receptors**: - Type Aδ fibers, thinly myelinated, transmit signals at **20 m/sec** - Some **type C fibers** may also function as cold receptors, suggesting a role for free nerve endings - **Warmth Receptors**: - Likely **free nerve endings**, transmit signals via unmyelinated **type C fibers** at **0.4 to 2 m/sec** - **Pain Receptors**: - Activated by **extreme cold and heat** - **Thermal Receptor Adaptation**: - Cold receptors adapt significantly but not fully, responding more strongly to **temperature changes** than to constant exposure - Transmission Pathways of Thermal Signals - **Mechanism of Receptor Stimulation**: - Thermal receptors likely respond to **temperature-driven metabolic rate changes** that affect intracellular chemical reactions - Temperature change rather than direct effect on nerve endings likely causes stimulation - **Transmission of Thermal Signals**: - Thermal signals follow pathways similar to **pain pathways** - Upon entering the spinal cord, they travel a few segments in **Lissauer's tract** and terminate in **laminae I, II, and III** - Ascend in the **anterolateral tract** to the **reticular formation** and **ventrobasal complex** of the thalamus - Some signals reach the **somatic sensory cortex**, though cortical removal reduces but doesn't abolish temperature discrimination - AUTONOMIC NERVOUS SYSTEM - The Autonomic Nervous System (ANS) - **Overview**: - The ANS regulates **visceral functions** such as **arterial pressure, gastrointestinal activity, urinary bladder control, sweating,** and **body temperature** - Known for its ability to make **rapid and intense adjustments** to internal organ functions - **Control Centers**: - **Brain Stem Reticular Substance**: - Located along the **tractus solitarius** in the medulla, pons, and mesencephalon - Controls **arterial pressure, heart rate, glandular secretion, gastrointestinal peristalsis,** and **urinary bladder contraction** - **Hypothalamus**: - Influences brain stem centers and autonomic functions - Regulates **body temperature, salivation, gastrointestinal activity,** and **bladder emptying** - **Effect of Brain Stem Transection**: - **Above midpontine level**: Basal control of **arterial pressure** remains, but higher modulation is lost - **Below medulla**: Arterial pressure drops significantly - ANS Control - **Activation Centers**: - ANS is activated mainly by the **brain stem** and **hypothalamus** - **Cerebral cortex** (especially the **limbic cortex**) can influence autonomic control by sending signals to lower centers - **Visceral Reflexes**: - The ANS often operates via **visceral reflexes** - **Sensory signals** from visceral organs can trigger reflex responses in **autonomic ganglia, brain stem,** or **hypothalamus** - Reflexes produce **subconscious control** of visceral organs - **Subdivisions**: - **Sympathetic Nervous System (SNS)**: - Prepares the body for \"fight or flight\" responses - **Parasympathetic Nervous System (PNS)**: - Controls \"rest and digest\" functions, promoting relaxation and conservation of energy - Organization of the SNS - **Sympathetic Pathways**: - **Two Main Structures**: - **Paravertebral sympathetic chains**: Interconnected ganglia beside the spinal column - **Prevertebral ganglia**: Includes **celiac, superior mesenteric, aorticorenal, inferior mesenteric,** and **hypogastric ganglia** - **Sympathetic Nerve Origin**: - Sympathetic nerve fibers originate between **T1 and L2** segments of the spinal cord - These fibers first enter the **sympathetic chain** before traveling to target organs - **Sympathetic Neuron Types**: - **Preganglionic Neurons**: Originate in the **intermediolateral horn** of the spinal cord - **Postganglionic Neurons**: Synapse in ganglia and travel to target organs - **Sympathetic Nervous System** - **Types of Autonomic Receptors** - **Cholinergic Receptors**: - **Muscarinic**: Found on all effector cells targeted by **postganglionic cholinergic neurons**; uses **G proteins** - **Nicotinic**: Located in **autonomic ganglia** at synapses between preganglionic and postganglionic neurons; **ligand-gated ion channels** - **Adrenergic Receptors**: - **Alpha Receptors**: - **Alpha1** and **Alpha2** receptors, linked to different **G proteins** - **Beta Receptors**: - Divided into **Beta1**, **Beta2**, and **Beta3**, each with distinct effects - Norepinephrine excites primarily **alpha receptors**; epinephrine excites both **alpha and beta** receptors - **ANS Neurotransmitters** - **ANS Neurotransmitter Synthesis and Secretion** - **Acetylcholine Synthesis**: - Produced in **terminal endings and varicosities** - Rapid breakdown by **acetylcholinesterase** into acetate and choline after release - **Norepinephrine Synthesis**: - Begins in the **axon terminal** and finishes in secretory vesicles - **Conversion Process**: - Tyrosine → Dopa → Dopamine → Norepinephrine → Epinephrine - Removed by: - **Reuptake** into nerve endings (50-80%) - **Diffusion** into surrounding fluids - **Enzyme destruction** (e.g., **monoamine oxidase**) - ANS Receptors - **Receptor Binding**: - **Receptors on effector cells** bind acetylcholine, norepinephrine, or epinephrine - Binding causes **conformational changes** in receptor protein - These changes **excite or inhibit** the cell through: - **Ion channel changes**: Alters membrane permeability (e.g., Na⁺, Ca²⁺ influx excites; K⁺ efflux inhibits) - **Enzyme activation**: Activates/inactivates enzymes inside the cell (e.g., adenylyl cyclase → cAMP) - Table 61.2 - ANS Tone - **Sympathetic and Parasympathetic Tone:** - **Normal Activity:** Both systems are continually active, known as **sympathetic tone** and **parasympathetic tone** - **Function of Tone:** Allows a single nervous system to both **increase** and **decrease** the activity of a stimulated organ - **Sympathetic Tone:** - Keeps systemic arterioles constricted to about **one-half** their maximum diameter - Can **increase** constriction with heightened sympathetic stimulation or **dilate** with decreased stimulation - **Parasympathetic Tone:** - Background "tone" in the **gastrointestinal tract** - Surgical removal of parasympathetic supply (e.g., cutting the **vagus nerves**) can lead to serious and prolonged **gastric and intestinal atony** - **Denervation Hypersensitivity** - Loss of tone occurs immediately after cutting a sympathetic or parasympathetic nerve - **Compensation:** Over time, intrinsic compensation develops, returning the function of the organ almost to its normal level - After nerve destruction, the organ becomes more sensitive to injected **norepinephrine** or **acetylcholine** - Example: Blood flow in the forearm increases markedly post-sympathetic tone loss, then shows enhanced responsiveness to norepinephrine due to increased receptor numbers - **Mass Discharge of the SNS** - **Mass Discharge:** - Activates large portions of the sympathetic nervous system simultaneously - **Effects on Body:** - **Increased arterial pressure** - **Increased blood flow** to active muscles and decreased blood flow to non-essential organs (e.g., **gastrointestinal tract**, **kidneys**) - **Increased cellular metabolism** rates throughout the body - **Increased blood glucose concentration** - **Increased glycolysis** in liver and muscle - **Increased muscle strength** - **Increased muscle activity** - **Increased blood coagulation rate** - **Sympathetic Stress Response:** - Purpose is to provide extra activation of the body during **mental** or **physical stress** - Commonly referred to as the **fight-or-flight reaction** - **Autonomic Reflexes** - Adrenal Medullae - **Release Mechanism:** - Stimulation of **sympathetic nerves** to the **adrenal medullae** results in the release of **epinephrine** and **norepinephrine** into the bloodstream - These hormones affect various organs similarly to direct sympathetic stimulation but last **5 to 10 times longer** (2 to 4 minutes) in the bloodstream - **Dual Mechanism of Action:** - Both hormones are released simultaneously with sympathetic activation, providing a **safety factor**; one mechanism compensates for the other if needed - They can also stimulate **structures** not directly innervated by sympathetic fibers - **Physiological Effects:** - **Norepinephrine**: - Causes **vasoconstriction** of most blood vessels - Increases **heart activity** - **Inhibits gastrointestinal activity** - **Dilates pupils** - **Epinephrine**: - Similar effects as norepinephrine but: - **Greater cardiac stimulation** due to beta receptor activation - Causes **weak vasoconstriction** in muscle blood vessels - Increases **metabolic rate** (5 to 10 times more than norepinephrine) - CEREBRAL BLOOD FLOW,\ CEREBROSPINAL FLUID, AND CEREBRAL METABOLISM - **Cerebral Blood Flow** - **Arterial Supply:** - The brain is supplied by **four large arteries**: - **Two carotid arteries** - **Two vertebral arteries** - These arteries merge to form the **circle of Willis** at the base of the brain - **Branching of Arteries:** - Arteries from the circle of Willis travel along the **brain surface** - They give rise to **pial arteries** that branch into smaller vessels called **penetrating arteries** and **arterioles** - **Penetrating Vessels:** - The penetrating vessels are separated from brain tissue by the **Virchow-Robin space**, an extension of the **subarachnoid space** - These vessels dive into the brain tissue, forming **intracerebral arterioles** that branch into **capillaries** for nutrient and gas exchange - **Regulation of Cerebral Blood Flow** - **Cerebral Blood Flow:** - Normal blood flow averages **50 to 65 mL / 100 g** of brain tissue/min, totaling **750 to 900 mL/min** for the entire brain - The brain receives **15% of the resting cardiac output** despite constituting only **2% of body weight** - **Metabolic Regulation:** - Key metabolic factors influencing blood flow: - **CO2 concentration** - **Hydrogen ion (H+) concentration** - **O2 concentration** - Substances released from **astrocytes** - **Response to CO2:** - Increased **CO2** leads to vasodilation; a **70% increase** in arterial CO2 can **double cerebral blood flow**. - CO2 forms **carbonic acid**, dissociating into **H+**, causing vessel dilation - **O2 Utilization:** - O2 utilization remains stable at **3.5 mL O2 / 100 g** of brain tissue/min - Insufficient O2 supply causes vasodilation to restore blood flow - **Astrocytic Influence:** - Astrocytes release **vasoactive metabolites** that mediate local vasodilation in response to neuronal activity - Cerebral Microcirculation - **Capillary Density:** - The number of **blood capillaries** in the brain is highest where **metabolic needs** are greatest - The **metabolic rate** of brain gray matter is about **four times** that of white matter, leading to a correspondingly higher number of capillaries and blood flow - **Capillary Structure:** - Brain capillaries are much less **"leaky"** compared to those in other tissues - Supported by **glial feet** from surrounding glial cells (e.g., astrocytes), providing physical support and preventing overstretching under high pressure - **Response to High Blood Pressure:** - **Arterioles** leading to brain capillaries thicken in response to high blood pressure, maintaining **constriction** to protect capillaries from high pressure - Breakdown of protective mechanisms can lead to **serious brain edema**, potentially resulting in **coma** and **death** - **Autoregulation of Cerebral Blood Flow** - **Normal Fluctuations:** - Arterial pressure fluctuates widely during daily activities, rising during **excitement** or **strenuous activity** and falling during **sleep** - Cerebral blood flow is **autoregulated** well between arterial pressure limits of **60** and **150 mm Hg** - **Hypertension Effects:** - Chronic **hypertension** leads to **hypertrophic remodeling** of cerebral blood vessels, shifting the autoregulatory curve to **higher blood pressures** - This adaptation partially protects against high blood pressure but increases vulnerability to **ischemia** if pressure drops too rapidly - **Impairment of Autoregulation:** - Impaired autoregulation makes cerebral blood flow more dependent on arterial pressure - Conditions such as **preeclampsia** may disrupt autoregulation, causing pressure-dependent increases in cerebral blood flow, **edema**, and seizures - In **old age**, **atherosclerosis**, and various brain disorders, autoregulation impairment increases the risk of brain injury related to blood pressure fluctuations - Cerebrospinal Fluid - **Cranial Vault:** - The entire cerebral cavity has a capacity of approximately **1600 to 1700 mL** - About **150 mL** of this capacity is occupied by **cerebrospinal fluid (CSF)** - **Location of CSF:** - Present in the **ventricles** of the brain - Located in **cisterns** around the brain - Found in the **subarachnoid space** surrounding the brain and spinal cord - **Connection and Pressure Regulation:** - All chambers containing CSF are interconnected - The pressure of the CSF is maintained at a surprisingly **constant level** - Function of Cerebrospinal Fluid - **Cushioning Effect:** - The cerebrospinal fluid (CSF) cushions the brain within its **solid vault** - The brain and CSF have about the same **specific gravity**, allowing the brain to **float** in the fluid - **Formation and Flow of Cerebrospinal Fluid** - **Production Rate:** - CSF formed at a rate of about **500 mL/day** - **Two-thirds** originates from the **choroid plexus** in the ventricles - **Choroid Plexus:** - Cauliflower-like growth of blood vessels covered by epithelial cells - **Active transport** of sodium ions drives fluid secretion into the ventricles - **Fluid Characteristics:** - Osmotic pressure approximately equal to plasma - **Sodium concentration:** similar to plasma - **Chloride concentration:** about **15% greater** than plasma - **Potassium concentration:** approximately **40% less** than plasma - **Glucose concentration:** about **30% less** than plasma - **Flow Pathway:** - CSF flows from the **lateral ventricles** to the **third ventricle**, down the **aqueduct of Sylvius** to the **fourth ventricle** - Exits the fourth ventricle through foramina into the **cisterna magna**, then into the **subarachnoid space** - **Arachnoidal Villi:** - Microscopic projections that allow CSF to flow into the **venous sinuses** - Arachnoidal granulations can be seen protruding from the sinuses - Cerebrospinal Fluid Pressure - **Normal Pressure:** - Average pressure: **130 mm of water (10 mm Hg)** - Ranges from **65 mm to 195 mm** of water in healthy individuals - **Pressure Regulation:** - Arachnoidal villi function as **valves** for CSF flow - CSF pressure must be about **1.5 mm Hg** greater than venous blood pressure for flow to occur - Blood-Brain Barrier - **Blood-Brain Barrier (BBB):** - Exists between **blood vessels** and **brain parenchyma** - Facilitates transport of certain hormones (e.g., **leptin**) into the **hypothalamus** - Highly permeable to: - **Glucose**, **hormones**, **CO2**, **O2**, and most **lipid-soluble substances** (e.g., alcohol) - Slightly permeable to **electrolytes**; almost impermeable to: - **Plasma proteins** and most **non-lipid-soluble** large organic molecules - **Blood-Cerebrospinal Fluid Barrier:** - Similar permeability characteristics as the BBB - **Tight junctions** between endothelial cells limit permeability - **Brain Metabolism and Energy Supply** - **Resting Brain Metabolism:** - Accounts for **15%** of total body metabolism despite being only **2%** of body mass - Metabolism per unit mass: about **7.5 times** that of non-nervous tissues - **Neuronal vs. Glial Metabolism:** - Most brain metabolism occurs in **neurons** - Major metabolic need: Pumping ions (sodium, calcium, potassium) across membranes - High activity can increase metabolism by **100% to 150%** - **Dependence on Oxygen:** - Brain has limited anaerobic metabolism; relies on continuous **O2** delivery - Sudden cessation of blood flow can cause **unconsciousness** within **5 to 10 seconds** - **Glucose Supply:** - Almost all energy for brain cells comes from **glucose** - Glucose transport into neurons is **insulin-independent** - Diabetic patients may experience low blood glucose levels, risking mental function impairment and possible **coma**