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Nerve Anatomy
1. Overview
A peripheral nerve is not a single wire - it is an organized bundle of many individual nerve fibers (axons), each with its own cellular sheath, wrapped together in layers of connective tissue and supplied by a dedicated blood system.
2. Connective Tissue Layers (Inside Out)
The three concentric connective tissue sheaths are the structural backbone of every peripheral nerve:
Endoneurium
- The innermost layer; loose connective tissue (reticular fibers, sparse fibroblasts, capillaries) that surrounds each individual nerve fiber (axon + Schwann cell)
- Collagen fibrils run both parallel to and circumferentially around the fiber; most are secreted by Schwann cells
- Contains mast cells and macrophages for immune surveillance and repair
- Sparse capillaries here form part of the blood-nerve barrier
- Histology A Text and Atlas With Correlated Cell and Molecular Biology, p. 981-982
Perineurium
- Groups of nerve fibers + endoneurium are bundled into fascicles by the perineurium
- 2-6 layers of flat, specialized fibrocyte-like cells with edges sealed by tight junctions - these create the main blood-nerve barrier that regulates the fascicular microenvironment
- Cells have actin microfilaments, pinocytotic vesicles, and cytoplasmic densities, resembling smooth muscle cells ultrastructurally
- Perineurial cell processes can extend inward to surround sub-groups of axons at branching points
- Junqueira's Basic Histology, 17e, p. 469-470
Epineurium
- Dense irregular fibrous coat that surrounds the entire nerve trunk and fills the spaces between fascicles
- Has a superficial dense region and a deeper, looser region containing larger blood vessels
- Extends as interfascicular epineurium between fascicle groups
- Current Surgical Therapy 14e, p. 980
Mesoneurium
- Loose connective tissue extending from the epineurium to surrounding tissues
- Allows nerve gliding during range of motion and carries the segmental (extrinsic) blood supply to the nerve
- Campbell's Operative Orthopaedics 15th Ed, p. 3840
Figure: Epi-, peri-, and endoneurium. (a) 3D diagram; (b) H&E histology showing fascicles (N), perineurium (P), epineurium (E), artery (A), vein (V); (c) perineurial septa (S) within a fascicle; (d) SEM of a single fascicle showing myelinated axons and endoneurium. - Junqueira's Basic Histology, 17e
Figure: Full cross-sectional anatomy showing fascicles, perineurium, external epineurium, interfascicular epineurium, endoneurium, nerve fiber, and mesoneurium. - Current Surgical Therapy 14e
3. The Individual Nerve Fiber
Each nerve fiber = axon + Schwann cell sheath.
Myelinated Fibers
- A single Schwann cell rotates around one axon many times, laying down multiple layers of its membrane (containing sphingomyelin) - this is the myelin sheath
- Myelin is an electrical insulator that reduces ion flow ~5000-fold
- The segment of fiber covered by one Schwann cell = internode (0.1-1.8 mm; longer internodes on more heavily myelinated fibers)
- The gap between successive Schwann cells, where the axon membrane is exposed = node of Ranvier (2-3 µm long)
- Action potentials jump from node to node = saltatory conduction - this increases velocity 5-50 fold and is energy efficient
- Guyton & Hall Medical Physiology, p. (Ch. 5)
Unmyelinated Fibers
- Several axons (~10-20) are embedded within the cytoplasmic processes of a single Schwann cell (Remak cell) but are not wrapped
- Conduct impulses slowly by continuous conduction along the membrane
- Unmyelinated fibers outnumber myelinated ~2:1 in a typical nerve trunk
- Sensory and motor nerves have unmyelinated:myelinated ratio of ~4:1
Figure: (A) Single Schwann cell wrapping around one large axon forming myelin sheath with node of Ranvier. (B) One Schwann cell partially wrapping multiple unmyelinated axons (Remak bundle). - Guyton & Hall
Figure: Axon, myelin, Schwann cell nucleus/membrane, internode, node (nodal gap), and basal lamina. - Campbell's Operative Orthopaedics, 15e
4. Nerve Fiber Classification
Two classification systems are in use - the Erlanger-Gasser (letter) system and the Lloyd-Hunt (Roman numeral) system for sensory fibers only.
Erlanger-Gasser Classification (Ganong's Review of Medical Physiology, 26e)
| Fiber Type | Function | Diameter (µm) | Velocity (m/s) | Myelinated? |
|---|
| Aα | Proprioception; somatic motor (α motor neurons) | 12-20 | 70-120 | Yes |
| Aβ | Touch, pressure | 5-12 | 30-70 | Yes |
| Aγ | Motor to muscle spindles (intrafusal fibers) | 3-6 | 15-30 | Yes |
| Aδ | Pain (fast/sharp), temperature, touch | 2-5 | 12-30 | Yes |
| B | Preganglionic autonomic | <3 | 3-15 | Yes |
| C | Slow/aching pain, temperature; postganglionic autonomic | 0.3-1.3 | 0.5-2.3 | No |
Lloyd-Hunt Classification (Sensory Only - Costanzo Physiology, 7e)
| Type | Corresponds to | Example |
|---|
| Ia | Aα | Muscle spindle primary afferents |
| Ib | Aα | Golgi tendon organ afferents |
| II | Aβ | Muscle spindle secondary afferents; touch, pressure |
| III | Aδ | Touch, pressure, fast pain, temperature |
| IV | C | Slow pain, temperature |
Clinical note: Local anesthetics block unmyelinated C fibers before myelinated A fibers. Conversely, pressure on a nerve selectively blocks large-diameter A fibers (motor, touch, pressure) first, leaving pain (C fibers) relatively intact - the classic "arm fell asleep" pattern.
5. Fascicular Topography
- Proximally, sensory and motor axons intermingle significantly within nerve trunks
- More distally, they segregate into distinct motor and sensory fascicles
- This has direct surgical implications: proximal nerve repairs (e.g. facial nerve within the temporal bone) risk synkinesis/dyskinesis due to poorly differentiated fascicles; distal repairs have better outcomes because the fascicular architecture is more defined
- Current Surgical Therapy 14e, p. 980
6. Blood Supply
- Extrinsic (segmental) supply: enters through the mesoneurium at multiple points along the nerve
- Intrinsic (longitudinal) supply: runs within the epineurium and perineurium; branches penetrate into the endoneurium
- Endoneurial capillaries have tightly joined endothelium - a second component of the blood-nerve barrier
- This dual supply means peripheral nerves can tolerate moderate stretching or positional changes without ischemia
Summary: Structural Hierarchy
Nerve trunk
└── Epineurium (dense irregular CT)
└── Fascicles (grouped by interfascicular epineurium)
└── Perineurium (tight-junction sealed fibrocytes)
└── Individual nerve fibers
└── Endoneurium (loose CT)
└── Axon + Schwann cell (± myelin)
Sources: - Junqueira's Basic Histology, 17e | Histology: A Text and Atlas (Ross), 8e | Guyton & Hall Medical Physiology | Ganong's Review of Medical Physiology, 26e | Costanzo Physiology, 7e | Campbell's Operative Orthopaedics, 15e | Current Surgical Therapy, 14e