26169.jpg

Explain all these thoroughly for first year mbbs

Reading File

Finding Sources

Reading File

Loading Image

Reading File

Loading Image

I now have excellent content from the textbooks. Let me compile the comprehensive answer for the 1st year MBBS student.

SGD Topics - 1st Year MBBS Physiology

Sahiwal Medical College | Tutor: Dr. Aroona

1. Properties of Synapse

A synapse is the specialized junction between two neurons (or between a neuron and an effector) where information is transmitted. It has two sides: the presynaptic terminal (sending side) and the postsynaptic membrane (receiving side), separated by a synaptic cleft of 200-300 Angstroms (Å).

Chemical synapse showing Ca²⁺ entry, synaptic vesicles, neurotransmitter release, and postsynaptic receptors

Chemical synapse anatomy - Guyton & Hall Medical Physiology

Types of Synapses

Feature	Chemical Synapse	Electrical Synapse
Transmission medium	Neurotransmitter	Gap junctions (ion current)
Direction	One-way only	Bidirectional
Synaptic cleft	200-300 Å	Very narrow / absent
Speed	Slight delay (1ms)	Instantaneous
Main role	Most CNS synapses	Synchronizing neuronal groups

Key Properties of Chemical Synapses

1. One-way (Unidirectional) Transmission Chemical synapses only transmit from the presynaptic to the postsynaptic neuron. This is because only the presynaptic terminal contains synaptic vesicles and only the postsynaptic membrane has receptors. This directionality allows precise signal routing.

2. Synaptic Delay There is a delay of about 0.5 ms at each synapse. This time accounts for: Ca²⁺ entry into the terminal → vesicle docking → exocytosis → neurotransmitter diffusion → receptor binding. Pathways with many synapses have longer total delays.

3. Summation (Spatial and Temporal) A single presynaptic terminal discharge does NOT produce enough EPSP to fire the postsynaptic neuron. About 40-80 terminals must fire simultaneously. There are two types:

Spatial summation: Multiple presynaptic terminals fire at the same time
Temporal summation: A single terminal fires in rapid succession, building up EPSP

4. Excitatory Postsynaptic Potential (EPSP) When an excitatory transmitter (e.g., glutamate) binds, Na⁺ rushes in, raising the membrane potential from -65 mV toward 0 mV (to about -45 mV). If EPSP reaches the threshold at the axon hillock (initial segment), an action potential fires. The axon hillock has 7x more voltage-gated Na⁺ channels than the soma, making it the site of AP generation.

5. Inhibitory Postsynaptic Potential (IPSP) Inhibitory transmitters (e.g., GABA, glycine) open K⁺ or Cl⁻ channels, making the membrane MORE negative (e.g., -65 → -70 mV) - called hyperpolarization. This makes it harder to reach firing threshold.

6. Fatigue With repeated high-frequency stimulation, the synapse fatigues - synaptic vesicles deplete, the postsynaptic response diminishes. This is a protective mechanism preventing excessive nervous system stimulation.

7. Effect of Calcium Ca²⁺ entry through voltage-gated calcium channels in the presynaptic terminal is absolutely necessary for vesicle exocytosis. Without Ca²⁺, no neurotransmitter is released. The SNARE protein complex (synaptobrevin, syntaxin, SNAP-25) mediates vesicle docking and fusion.

8. Neurotransmitters

Small-molecule, fast-acting: Acetylcholine, glutamate, GABA, glycine, dopamine, norepinephrine, serotonin
Neuropeptides, slow-acting: Substance P, enkephalins, endorphins (cause longer-lasting effects, act on second messenger systems)

9. Post-tetanic Potentiation After a burst (tetanus) of presynaptic stimulation, subsequent stimuli produce a larger than normal postsynaptic response for a period - due to residual Ca²⁺ in the presynaptic terminal.

10. Sensitization and Habituation Synaptic responses can increase (sensitization) or decrease (habituation) with repeated stimulation - this forms the cellular basis of learning and memory.

2. Axonal Transport

The cell body (soma) is the metabolic engine of the neuron. All proteins are synthesized there (since axons lack ribosomes). Yet the axon terminal can be 1 meter or more away - so a transport system is needed to ship proteins down (and return signals up).

Kinesin walking along microtubules in anterograde axonal transport

Kinesin motor protein walking along microtubules - Neuroscience: Exploring the Brain

Types of Axonal Transport

Type	Direction	Speed	Motor Protein	What is Carried
Fast anterograde	Soma → Terminal	~400 mm/day	Kinesin	Synaptic vesicles, membrane organelles, enzymes
Slow anterograde	Soma → Terminal	0.5-10 mm/day	Kinesin	Cytoskeletal proteins (actin, tubulin), metabolic enzymes
Retrograde	Terminal → Soma	~200 mm/day	Dynein	Used vesicles, NGF, viral particles, toxins

Mechanism

The axon contains microtubules running along its length like railway tracks
Kinesin is the motor protein for anterograde transport - it "walks" toward the (+) end of microtubules (toward the terminal), using ATP
Dynein is the motor protein for retrograde transport - it "walks" toward the (-) end (toward the soma), also using ATP
Material is packaged in membrane-bound vesicles

Clinical Importance

Herpes zoster and polio virus travel by retrograde transport to reach the cell body
Tetanus toxin travels retrogradely to the spinal cord
Nerve Growth Factor (NGF) travels retrogradely to signal the soma about conditions at the terminal
Interrupting axonal transport (as in axonal injury) leads to Wallerian degeneration (see below)
This is why the cell body maintains the functional integrity of the entire axon

Source: Ganong's Review of Medical Physiology, 26th Ed.; Neuroscience: Exploring the Brain, 5th Ed.

3. Nerve Injury

Peripheral nerve injuries are classified by the Seddon Classification (clinical) and the Sunderland Classification (anatomical):

Seddon Classification

Grade	Name	What is Damaged	Recovery
1st	Neurapraxia	Myelin only (conduction block)	Full, within weeks
2nd	Axonotmesis	Axon cut, endoneurium intact	Good, Wallerian degeneration occurs
3rd	Neurotmesis	Entire nerve (including connective tissue) severed	Poor without surgery

Sunderland Classification

Grade	Injury	Recovery
I	Focal demyelination (=neurapraxia)	Complete
II	Axon + myelin disrupted, endoneurium intact (=axonotmesis)	Good
III	Axon, myelin, endoneurium disrupted; perineurium intact	Variable
IV	Only epineurium intact	Poor
V	Complete severance (=neurotmesis)	None without surgery

Segmental Demyelination (Grade I / Neurapraxia)

Only a focal segment of the myelin sheath is damaged
The axon itself is intact
Results in slowing of conduction velocity or conduction block across that segment
Recovery occurs by remyelination within weeks to months
New myelin is thinner with more internodes

4. Wallerian Degeneration

Named after Augustus Waller (1850), who observed that cutting a nerve causes degeneration of the segment distal to the cut.

Wallerian degeneration - chromatolysis in cell body, axon and myelin degeneration distally, macrophage infiltration

Wallerian degeneration following axotomy - Bradley & Daroff's Neurology

What Triggers It?

Disruption of normal anterograde axonal transport from the soma to the distal axon. Without the soma's supply, the distal axon degenerates.

Changes Distal to the Injury (Days 1-7)

Day 1-2: Axon becomes irregular and granular; rapid influx of Ca²⁺ and Na⁺ through the disrupted membrane activates calcium-dependent proteases
Day 3: Schwann cells retract from nodes of Ranvier; activated Schwann cells and macrophages begin digesting the myelin - forming myelin ovoids
Day 7: The entire distal axon degenerates; macrophages (recruited by cytokines) phagocytose myelin debris - this entire process takes approximately 1 week
After cleanup: Schwann cells proliferate and form Bands of Büngner - longitudinal tubes that serve as guides for regenerating axons

Changes Proximal to the Injury

A limited degree of axon breakdown extends proximally up to the first node of Ranvier
The cell body undergoes CHROMATOLYSIS:
- Nissl substance (rough endoplasmic reticulum) breaks up and disperses
- Cell nucleus shifts to an eccentric (peripheral) position
- Cell body swells
- This represents a metabolic shift from axon maintenance to protein synthesis - preparing for regeneration
In very proximal injuries (e.g., root avulsion), the cell body itself may undergo apoptosis

Changes at the Target Organ

If the nerve does not regenerate in time, the denervated muscle undergoes atrophy and collagen deposition in endomysium/perimysium
Target organs must remain viable for successful reinnervation

5. Nerve Regeneration

Axon sprout with growth cone, filopodia, lamellipodia advancing through Bands of Büngner guided by Schwann cells

Growth cone of a regenerating axon - Bradley & Daroff's Neurology

How Regeneration Begins

After Wallerian degeneration clears the distal segment, the proximal stump sprouts new axon buds. This process depends on the type of injury:

1. Remyelination (Grade I / Focal Demyelination Only)

Schwann cells divide and remyelinate the damaged segment
Recovery of function within weeks to months
New myelin is thinner with more internodes per original internode

2. Collateral Sprouting (Partial Nerve Injury)

When some (not all) axons to a muscle are damaged
Intact motor axons produce sprouts from:
- Nodes of Ranvier → nodal sprouts
- Nerve terminals → terminal sprouts (as early as 4 days after injury)
These sprouts adopt denervated muscle fibers, increasing motor unit size
Clinical recovery takes 3-6 months

3. Proximal-to-Distal Regeneration (Severe/Complete Injury, Grades II-V)

The step-by-step sequence:

Axon sprouting from the proximal stump begins (stimulated by chromatolysis)
A growth cone forms at the tip of each sprout - it has:
- Filopodia (finger-like projections that sense the environment)
- Lamellipodia (sheet-like projections)
The growth cone is guided through Bands of Büngner (the tunnels left by Schwann cells in the distal stump) toward the target
Neurotropism: Guidance molecules (semaphorins, ephrins, netrins, slits) attract or repel the growth cone
Neurotrophic factors that promote regeneration: NGF, BDNF, NT-3, NT-4, GDNF, CNTF, FGF, IGF
Growth cone secretes plasminogen activators to dissolve cellular debris blocking the path

Rate of Regeneration

Proximal lesions: 2-3 mm/day
Distal lesions: ~1 mm/day
Average: ~1 inch (~25 mm) per month (classic teaching point)

Factors Affecting Regeneration

Factor	Effect
Intact endoneurial tube	Improves success significantly
Disrupted endoneurial tube	Axons may stray, forming neuroma (source of neuropathic pain)
Delay >4 months to cross gap	Distal tube shrinks to <3 μm, impedes recovery
Age	Younger patients regenerate better
Proximal vs distal injury	Proximal injuries have poorer outcome (longer time to target)
Denervated muscle >2 years	Irreversible fibrosis, no reinnervation possible

Clinical Note on Neuroma

When regenerating axons stray into surrounding connective tissue (due to disrupted endoneurium), they form a disorganized tangle called a neuroma. Sodium channels accumulate at this site, generating ectopic firing and neuropathic pain.

Summary Table for Quick Revision

Topic	Key Numbers / Points to Remember
Synaptic cleft width	200-300 Å
Presynaptic terminals on motor neuron	10,000-200,000
Terminals needed for EPSP→AP	40-80
Synaptic delay	~0.5 ms
Fast anterograde transport	~400 mm/day; motor: kinesin
Slow anterograde transport	0.5-10 mm/day
Retrograde transport	~200 mm/day; motor: dynein
Wallerian degeneration completes	~1 week distal to injury
Chromatolysis	Cell body response to axon injury
Collateral sprouting onset	4 days after injury
Nerve regeneration rate	1-2 mm/day (~1 inch/month)
Max time for reinnervation	~2 years

Sources: Guyton & Hall Textbook of Medical Physiology; Ganong's Review of Medical Physiology, 26th Ed.; Neuroscience: Exploring the Brain, 5th Ed.; Bradley & Daroff's Neurology in Clinical Practice

This is a shared conversation. Sign in to Orris to start your own chat.