Pathophysiology of Nervous System

Basic Anatomical and Physiological Aspects

The nervous system is a specialized network designed for communication between the organism and its external environment, as well as for internal integration of all bodily functions into a coordinated whole (the organic union). This system works in concert with the endocrine system to maintain homeostasis and adapt to continuous changes in external energy sources.

Any environmental change acts as a stimulus, eliciting a response from the organism. The nature of the response is determined by both genetic factors and external conditions, forming a feedback loop between stimulus and response.

Stimulus: A specific change in the internal or external environment that affects the nervous system, leading to impulse generation.
Impulse: An electrical change that excites tissues and propagates along nerves or conductive membranes.

As organisms evolve, responses become more complex and selective. The nervous system develops the capacity for memory and learning, refining reactions based on experience.

Cellular Composition of the Nervous System

  • Receptors/Sensors: Specialized cells that detect stimuli.
  • Interneurons: Process information and facilitate communication within neural networks.
  • Neurons (Effector Neurons): Transmit commands to effector organs (e.g., muscles, glands).
  • Glial & Satellite Cells: Provide structural and metabolic support.

Neural Transmission & Synaptic Function

Neural circuits typically begin with a receptor that transduces a stimulus into membrane excitation, which then propagates through interconnected neurons.

Synaptic Transmission

Impulses are transmitted between neurons via synapses through either:

  1. Electrical transmission (direct flow of ionic current)
  2. Humoral transmission (via chemical neurotransmitters)

Neurotransmitters are synthesized in neuron cell bodies, transported along axons, and stored in membrane-bound vesicles. Upon stimulation (often involving Ca²⁺ influx), vesicles fuse with the presynaptic membrane, releasing neurotransmitter into the synaptic cleft.

The neurotransmitter binds to receptors on the subsynaptic membrane, leading to either:

  • Depolarization (Excitation): Increased Na⁺ permeability.
  • Hyperpolarization (Inhibition): Increased K⁺ or Cl⁻ permeability.

Thus, synapses are classified as excitatory or inhibitory, though they are morphologically indistinguishable.

Note: Some neurons release transmitters into the bloodstream, acting as neuroendocrine cells, blurring the line between neural and endocrine signaling.

Organization of the Human Nervous System

The human nervous system exhibits hierarchical organization with three primary levels:

  1. Medulla Oblongata: Most primitive level, governing vital reflexes.
  2. Subcortical Areas: Intermediate processing and integration centers.
  3. Cortical Areas: Highest level for complex analysis, learning, and conscious thought.

Evolutionarily, there is a shift of functions from medulla to brain (cranialization) and within the brain from subcortical areas to cortex (corticalization). Humans exhibit the greatest centralization and integration, with reduced autonomy of lower centers.

A key organizational principle is the combination of stable reflex mechanisms with high plasticity—the ability to adapt through learning and memory formation. Higher centers generally show greater plasticity than lower ones.

Structural Divisions

  • Central Nervous System (CNS): Brain and spinal cord.
  • Peripheral Nervous System (PNS): Cranial nerves (12 pairs), spinal nerves (31 pairs), ganglia, and plexuses.
  • Autonomic Nervous System (ANS): Sympathetic and parasympathetic divisions regulating involuntary functions.

Brain Structure & Functional Localization

The brain is divided into three major developmental divisions:

1. Forebrain (Prosencephalon)

Includes telencephalon (cerebral cortex) and diencephalon (thalamus, hypothalamus). The cerebral cortex, with its gyri and sulci, contains ~15 billion neurons and is responsible for higher nervous functions (analysis, integration, conscious thought). The diencephalon acts as a relay station and houses autonomic and endocrine regulation centers.

2. Hindbrain (Rhombencephalon)

Comprises medulla oblongata, pons, and cerebellum. Contains vital centers for respiration, circulation, and cardiac activity. The cerebellum regulates muscle tone, coordination, and balance.

3. Midbrain (Mesencephalon)

Smallest but complex region containing subcortical visual, auditory, and motor centers, and pathways connecting higher and lower centers.

Important Consideration: While some functions (e.g., specific sensory or motor pathways) are precisely localized, complex functions (consciousness, language, sleep) involve diffuse networks and cannot be pinpointed to a single anatomical site. This has crucial implications for clinical topical diagnosis of neurological lesions.

Basic CNS Functional Processes

CNS centers operate via principles of summation (temporal and spatial) and occlusion. The final response is modulated by neurons outside the main afferent pathway that are sensitized or depressed.

Core processes are stimulation (increased synaptic conduction) and depression (decreased or blocked transmission). These processes exhibit induction:

  • Spatial Induction: Stimulation in one area induces depression in adjacent areas, and vice versa.
  • Temporal Induction: A primary reaction is followed by an opposite after-effect.
Reverberation: Afferent stimuli can circulate in neuronal loops, leading to repeated stimulation or inhibition. This phenomenon is implicated in learning, memory, and pathological states like epilepsy (kindling effect).

The Reflex Arc

The basic functional unit is the reflex arc, comprising:

  1. Receptor
  2. Afferent (sensory) pathway
  3. Integration center (CNS)
  4. Efferent (motor) pathway
  5. Effector (muscle/gland)

Reflexes can be monosynaptic (direct, e.g., proprioceptive) or polysynaptic (indirect, involving interneurons, e.g., defensive reflexes). They are categorized as unconditional (innate) or conditional (acquired).

CNS Protection & The Blood-Brain Barrier

The CNS is physically protected by the skull and vertebral column. However, this rigidity becomes a disadvantage when intracranial pressure increases, leading to brain compression.

The brain is suspended in cerebrospinal fluid (CSF) within the meningeal layers:

  • Dura Mater: Tough outer layer; potential space for epidural lesions.
  • Arachnoid Mater: Middle layer; subarachnoid space contains CSF and vessels.
  • Pia Mater: Innermost layer, closely adhering to brain surface; forms part of the blood-brain barrier (BBB).
Blood-Brain Barrier (BBB): A selective barrier formed by capillary endothelial cells, astrocyte foot processes, and a basement membrane. It regulates molecular passage between blood and brain tissue, protecting the CNS from toxins and pathogens while maintaining homeostasis.

CSF composition resembles brain extracellular fluid, but its changes have only minor indirect effects on brain tissue in most diseases. The BBB separates two compartments of different embryonic origin: neuroectodermal (neurons, neuroglia) and mesodermal (vessels, meninges, microglia).

6.2 Neuronal Injury

Neurons are highly vulnerable to various insults:

  • Anoxia & Hypoglycemia
  • Viral Infections
  • Metabolic Disorders
  • Vitamin Deficiencies (e.g., B vitamins)

The impact depends on the injury site, neuron type, degree of differentiation, and relationship with glial cells. Injuries range from reversible functional disturbances to irreversible cell death.

Degrees of Neuronal Injury

  1. Functional Injury: Reversible (e.g., transient hypoxia).
  2. Axonal Death: Without disruption of endoneural tubes (potential for regeneration).
  3. Axonal Death with Tube Interruption: Severe, often irreversible damage.
Clinical Relevance: Understanding the susceptibility of neurons to metabolic and toxic insults is fundamental in pharmacotherapy for neurological disorders, neuroprotective strategies, and management of adverse drug effects on the CNS.