Day 106 NEET PG

Chapter: General Physiology; Topic: Body Fluids; Subtopic: Interstitial Fluid and Volume Measurement

Key Definitions & Concepts

• Interstitial Fluid (ISF): The fluid that fills the spaces between cells (interstitium); it constitutes the immediate environment of the body's cells (Internal Environment).

• Extracellular Fluid (ECF): The total fluid outside the cells, comprising two main sub-compartments: Plasma (intravascular) and Interstitial Fluid (extravascular).

• Indirect Measurement: The method used to quantify compartments for which no specific tracer exists; ISF is calculated, not measured directly.

• Plasma Volume: The fluid portion of the blood, measured directly using Evans Blue dye or Radio-iodinated Albumin.

• Total Body Water (TBW): The sum of Intracellular Fluid (ICF) and Extracellular Fluid (ECF); measured using Deuterium Oxide.

• Inulin: The classic substance used to measure ECF volume because it crosses capillary walls but not cell membranes.

• Starling Forces: The hydrostatic and oncotic pressures that govern the exchange of fluid between the plasma and the interstitial fluid.

• Lymphatic System: The drainage system that returns excess interstitial fluid and proteins back to the circulation; failure leads to lymphedema.

• Gel Matrix: In tissues, much of the interstitial fluid is trapped within a proteoglycan meshwork, preventing free flow (except in edema).

• Gibbs-Donnan Effect: Causes the concentration of diffusible cations (like Na+) to be slightly lower in ISF than in plasma due to the lack of proteins in ISF.

Lead Question - 2016

Calculation of interstitial fluid in a 50 years old is done by?

a) TBW minus ECF

b) ECF minus plasma volume

c) ICF minus ECF

d) TBW minus ICF

Explanation: The Extracellular Fluid (ECF) is the sum of the Plasma Volume (fluid inside vessels) and the Interstitial Fluid (fluid between cells). There is no single substance that distributes *exclusively* into the interstitial space without also entering the plasma. Therefore, Interstitial Fluid (ISF) cannot be measured directly using the dilution method. Instead, it must be calculated indirectly. We first measure the total ECF volume (using Inulin or Mannitol) and the Plasma Volume (using Evans Blue). Subtracting the Plasma Volume from the total ECF gives the volume of the Interstitial Fluid. Formula: ISF = ECF - Plasma Volume. Therefore, the correct answer is b) ECF minus plasma volume.

1. Interstitial Fluid typically constitutes what proportion of the total Extracellular Fluid (ECF) volume?

a) 1/4

b) 1/3

c) 1/2

d) 3/4

Explanation: The Extracellular Fluid (ECF) makes up about 20% of the total body weight (approx. 14 liters in a 70kg man). This ECF is subdivided into Plasma and Interstitial Fluid. Plasma volume is roughly 3.5 liters, which is 1/4 of the ECF. The remaining fluid, which bathes the cells, is the Interstitial Fluid. It accounts for approximately 10.5 liters, which represents 3/4 (or 75%) of the Extracellular Fluid volume. This ratio is important when calculating fluid shifts during resuscitation. Therefore, the correct answer is d) 3/4.

2. Which of the following substances can be used to measure Interstitial Fluid Volume directly?

a) Radioactive Sodium

b) Heavy Water (D2O)

c) None; it is calculated indirectly

d) Evans Blue dye

Explanation: The "Indicator Dilution Principle" requires a marker to distribute exclusively in the compartment of interest. Markers for ECF (Inulin, Sodium) enter both Plasma and Interstitial fluid. Markers for Plasma (Evans Blue, Albumin) stay in Plasma. There is no known substance that, when injected into the blood, crosses the capillary wall into the interstitium but avoids remaining in the plasma. Consequently, Interstitital Fluid Volume cannot be measured directly. It is always a derived value obtained by subtracting Plasma Volume from ECF volume. Therefore, the correct answer is c) None; it is calculated indirectly.

3. The composition of Interstitial Fluid is most similar to that of Plasma, with the significant exception that Interstitial Fluid has:

a) Much higher Sodium concentration

b) Much lower Protein concentration

c) Much higher Potassium concentration

d) Much lower Bicarbonate concentration

Explanation: Plasma and Interstitial Fluid are separated by the capillary membrane, which is highly permeable to ions and small solutes but relatively impermeable to large plasma proteins. Therefore, the electrolyte concentrations (Na+, K+, Cl-) are very similar between the two compartments (governed by the Gibbs-Donnan effect). The defining difference is the Protein concentration. Plasma has a high protein content (~7 g/dL), creating oncotic pressure. Interstitial fluid has a very low protein concentration because proteins generally do not cross the capillary barrier. Therefore, the correct answer is b) Much lower Protein concentration.

4. Edema is defined as the accumulation of excess fluid in the interstitial space. Which Starling force, when increased, favors the filtration of fluid from the capillary into the interstitium?

a) Plasma Oncotic Pressure

b) Interstitial Hydrostatic Pressure

c) Capillary Hydrostatic Pressure

d) Interstitial Oncotic Pressure

Explanation: Fluid movement across capillaries is determined by the balance of Starling Forces. Forces pushing fluid out (Filtration) are Capillary Hydrostatic Pressure and Interstitial Oncotic Pressure. Forces pulling fluid in (Reabsorption) are Plasma Oncotic Pressure and Interstitial Hydrostatic Pressure. An increase in Capillary Hydrostatic Pressure (e.g., in heart failure or venous obstruction) pushes more fluid out of the vessel than can be reabsorbed or drained by lymphatics, leading to the accumulation of Interstitial Fluid (Edema). Therefore, the correct answer is c) Capillary Hydrostatic Pressure.

5. Due to the Gibbs-Donnan effect caused by plasma proteins, the concentration of diffusible cations (like Sodium) in the Interstitial Fluid is:

a) Slightly lower than in Plasma

b) Slightly higher than in Plasma

c) Exactly the same as in Plasma

d) Dependent on the hematocrit

Explanation: Plasma proteins behave as non-diffusible anions (negative charge). According to the Gibbs-Donnan equilibrium, these negative charges attract diffusible cations (Na+, K+) to the plasma side and repel diffusible anions (Cl-) to the interstitial side. Consequently, the concentration of cations is slightly higher (~5%) in the plasma than in the interstitium. Conversely, the concentration of cations (like Sodium) in the Interstitial Fluid is slightly lower than in the plasma. This is a subtle but theoretically important distinction in fluid physiology. Therefore, the correct answer is a) Slightly lower than in Plasma.

6. A calculated increase in Interstitial Fluid Volume without a change in Plasma Volume would most likely be indicated by which measurement combination?

a) Normal Inulin space, Normal Evans Blue space

b) Increased Inulin space, Normal Evans Blue space

c) Normal Inulin space, Increased Evans Blue space

d) Increased D2O space, Normal Inulin space

Explanation: Interstitial Fluid (ISF) = ECF - Plasma. ECF is measured by the Inulin space. Plasma is measured by the Evans Blue space. If ISF increases (e.g., edema) but Plasma volume remains normal: 1. Plasma Volume (Evans Blue space) = Normal. 2. ISF = Increased. 3. ECF (Sum of Plasma + ISF) must be Increased. Therefore, the measurements would show an Increased Inulin space (reflecting the larger total ECF) alongside a Normal Evans Blue space. Subtracting the normal plasma from the large ECF yields a large ISF. Therefore, the correct answer is b) Increased Inulin space, Normal Evans Blue space.

7. Which of the following is a function of the lymphatic system regarding Interstitial Fluid dynamics?

a) To secrete proteins into the interstitium

b) To generate hydrostatic pressure for filtration

c) To return excess fluid and leaked proteins to the circulation

d) To actively transport Sodium into the interstitium

Explanation: In normal physiology, capillary filtration slightly exceeds reabsorption (by about 2-4 liters/day). Additionally, small amounts of plasma proteins inevitably leak into the interstitial space. The Lymphatic system acts as a scavenger mechanism. It collects this excess Interstitial Fluid and the leaked proteins and returns them to the venous circulation (via the thoracic duct). Without this function, protein would accumulate in the interstitium, abolishing the oncotic gradient, and fluid would build up, resulting in Lymphedema. Therefore, the correct answer is c) To return excess fluid and leaked proteins to the circulation.

8. "Third Spacing" refers to the accumulation of fluid in which compartment, rendering it physiologically unavailable for circulation?

a) Intracellular Fluid

b) Plasma

c) Functional Interstitial Fluid

d) Transcellular or Non-functional Interstitial spaces

Explanation: Fluid compartments are usually in dynamic equilibrium. "Third Spacing" describes the pathological sequestration of ECF into a space where it does not easily exchange with the rest of the ECF. This can be within body cavities (ascites, pleural effusion) or within traumatized tissues (bowel wall edema, severe burns). While anatomically often an extension of the interstitial or Transcellular space, functionally, this fluid is "lost" or trapped, leading to hypovolemia despite total body fluid overload. It is effectively a non-functional expansion of the interstitial/transcellular compartment. Therefore, the correct answer is d) Transcellular or Non-functional Interstitial spaces.

9. The interstitial fluid pressure in loose subcutaneous tissue is typically:

a) Subatmospheric (Negative)

b) Highly Positive (+10 mmHg)

c) Equal to arterial pressure

d) Equal to capillary oncotic pressure

Explanation: Measuring interstitial fluid pressure is difficult. However, using Guyton's capsule method or micropipettes, it has been determined that in loose subcutaneous tissues (where the skin is loose), the interstitial fluid pressure is Subatmospheric (Negative), roughly -3 to -6 mmHg relative to atmospheric pressure. This partial vacuum helps hold tissues together and prevents edema formation. The negative pressure is maintained by the constant pumping action of the lymphatics. If pressure becomes positive, free fluid accumulates (edema). Encapsulated organs (kidney) may have positive interstitial pressure. Therefore, the correct answer is a) Subatmospheric (Negative).

10. A specific marker used to measure Extracellular Fluid (ECF) volume must have all the following properties EXCEPT:

a) It must cross the capillary wall

b) It must penetrate the cell membrane

c) It should not be metabolized rapidly

d) It should not be toxic

Explanation: The ideal marker for measuring ECF volume (like Inulin, Mannitol, or Sucrose) must be able to leave the bloodstream to enter the interstitial space (cross capillary walls). Crucially, to measure only the ECF and not the Total Body Water, the marker Must NOT penetrate the cell membrane. If it entered the cells, it would measure TBW (like D2O). It also must be non-toxic, non-metabolized, and excreted relatively slowly or measurably to allow for equilibrium. Therefore, the correct answer is b) It must penetrate the cell membrane.

Chapter: General Physiology; Topic: Nerve-Muscle Physiology; Subtopic: Ionic Basis of Excitability

Key Definitions & Concepts

• Resting Membrane Potential (RMP): The baseline voltage across the cell membrane (-70 to -90 mV), determined primarily by the Potassium (K+) equilibrium potential due to high K+ permeability.

• Threshold Potential: The critical voltage level at which Voltage-Gated Sodium Channels (VGSCs) open explosively to generate an action potential.

• Potassium (K+): The major determinant of the Resting Potential. Changes in extracellular K+ (Hyperkalemia/Hypokalemia) shift the RMP closer to or further from the threshold.

• Calcium (Ca2+): The major determinant of the Threshold Potential. Extracellular Ca2+ stabilizes Na+ channels.

• Sodium (Na+): The major determinant of the Action Potential Amplitude (upstroke). Changes in [Na+] affect the height of the spike but have minimal effect on resting excitability.

• Hyperkalemia: High extracellular K+ depolarizes the membrane (makes RMP less negative), initially increasing excitability but potentially leading to depolarization block.

• Hypocalcemia: Low extracellular Ca2+ destabilizes Na+ channels, lowering the threshold potential (making it closer to RMP), causing tetany and hyperexcitability.

• Nernst Equation: Used to calculate the equilibrium potential for single ions; K+ has the most negative potential, anchoring the RMP.

• Chloride (Cl-): Primarily involved in inhibitory postsynaptic potentials (IPSPs) and stabilizing RMP, but less critical for spontaneous excitability changes than K+ or Ca2+.

• Excitability: The ease with which a cell can be triggered to fire an action potential; depends on the distance between RMP and Threshold.

Lead Question - 2016

Excitability of cells is maximally affected by change in concentration of which ion?

a) K+

b) Na+

c) Cl-

d) Ca+2

Explanation: The question asks about the *maximal* effect on *excitability*. Excitability is determined by the difference between the Resting Membrane Potential (RMP) and the Threshold Potential. 1. Potassium (K+): The RMP is primarily determined by the K+ gradient. Because extracellular K+ is very low (~4-5 mM), small absolute changes (e.g., rising to 7 mM) represent huge percentage changes. This significantly shifts the Nernst potential and the RMP. A shift in RMP directly alters the distance to the threshold. Thus, clinical changes in **Potassium (K+)** concentration have the most profound and direct effect on the resting excitability of cardiac and neural tissue (e.g., cardiac arrest in hyperkalemia). 2. Calcium (Ca2+): Affects the *Threshold*, but K+ affects the *Resting Potential*. Quantitatively, K+ disturbances are more common and dangerous causes of global excitability changes in clinical medicine. Therefore, the correct answer is a) K+ (interpreted from option 'a) IC+' which is likely a typo for K+).

1. Hypocalcemia (low extracellular Calcium) increases neuronal excitability causing tetany. This occurs because low Calcium:

a) Depolarizes the Resting Membrane Potential

b) Lowers the Threshold Potential (makes it more negative)

c) Blocks Potassium channels

d) Increases Sodium influx directly

Explanation: Extracellular Calcium ions bind to the outer surface of Voltage-Gated Sodium Channels, stabilizing them in the closed state. This "shielding" effect determines the voltage required to open the channels (the Threshold). In **Hypocalcemia**, this stabilizing effect is lost. Consequently, the sodium channels become easier to open; the **Threshold Potential lowers** (moves closer to the Resting Potential, e.g., from -55mV to -65mV). Because the gap between RMP (-70mV) and Threshold (-65mV) narrows, the cell becomes hyperexcitable and fires spontaneously, leading to tetany (Chvostek's sign). Therefore, the correct answer is b) Lowers the Threshold Potential (makes it more negative).

2. Which ion's equilibrium potential is closest to the Resting Membrane Potential of a typical neuron?

a) Sodium (+60 mV)

b) Potassium (-90 mV)

c) Calcium (+130 mV)

d) Chloride (-70 mV)

Explanation: The Resting Membrane Potential (RMP) is a weighted average of the equilibrium potentials of all permeant ions. The weighting factor is the membrane permeability. In the resting state, the membrane is highly permeable to **Potassium (K+)** due to open leak channels, and relatively impermeable to Sodium and Calcium. Because permeability to K+ is dominant, the RMP is pulled very close to the **Potassium Equilibrium Potential (-90 mV)**. It rests slightly less negative (e.g., -70 mV) due to a small contribution from Na+ leak. Therefore, the correct answer is b) Potassium (-90 mV).

3. Hyperkalemia (increased extracellular Potassium) initially causes increased excitability. However, severe or prolonged hyperkalemia can lead to paralysis and cardiac arrest due to:

a) Hyperpolarization block

b) Depolarization block (Accommodation)

c) Calcium channel blockade

d) Depletion of ATP

Explanation: High extracellular K+ depolarizes the cell (makes RMP less negative). Initially, this moves RMP closer to threshold (hyperexcitability). However, if the membrane remains persistently depolarized (e.g., at -50 mV), the Voltage-Gated Sodium Channels enter their **Inactivated State** (ball-and-chain closure). They cannot reset to the "closed-but-ready" state unless the membrane repolarizes. Since they remain chronically inactivated, they cannot open to generate an action potential. This refractory state is known as **Depolarization Block** or Accommodation, leading to muscle weakness/paralysis and asystole. Therefore, the correct answer is b) Depolarization block (Accommodation).

4. The amplitude (height) of the Action Potential is primarily dependent on the extracellular concentration of:

a) Potassium

b) Sodium

c) Calcium

d) Magnesium

Explanation: The upstroke (depolarization phase) of the action potential is driven by the rapid influx of Sodium (Na+) through voltage-gated channels. The membrane potential attempts to reach the Equilibrium Potential of Sodium (E-Na), which is typically around +60 mV. The peak voltage reached (overshoot) is determined by E-Na. According to the Nernst equation, E-Na depends on the ratio of extracellular to intracellular **Sodium**. Therefore, Hyponatremia (low extracellular Na+) will reduce the E-Na, resulting in a **smaller amplitude (shorter)** action potential, though it rarely affects the RMP or excitability significantly. Therefore, the correct answer is b) Sodium.

5. A change in the extracellular concentration of which ion would have the LEAST effect on the Resting Membrane Potential of a neuron?

a) Potassium

b) Chloride

c) Sodium

d) None, all affect it equally

Explanation: The GHK equation determines RMP based on permeability and concentration. The resting membrane has high permeability to K+ and moderate permeability to Cl-, but extremely **Low permeability to Sodium**. Because the permeability coefficient for Sodium ($P_{Na}$) is so small (approx 0.04 compared to 1.0 for K+), changing the extracellular **Sodium concentration** has a negligible effect on the resting potential. The membrane simply "ignores" the sodium gradient at rest. In contrast, small changes in K+ cause massive shifts in RMP. Therefore, the correct answer is c) Sodium.

6. In the treatment of severe Hyperkalemia (to prevent arrhythmias), Calcium Gluconate is administered. What is the mechanism of action of Calcium in this context?

a) It lowers serum Potassium levels

b) It raises the Threshold Potential, antagonizing the membrane depolarization

c) It hyperpolarizes the membrane directly

d) It blocks Potassium leak channels

Explanation: In hyperkalemia, the RMP becomes less negative (depolarized), moving it dangerously close to the threshold (e.g., RMP moves from -90 to -70, closer to a threshold of -65). This causes instability. Calcium Gluconate does not lower K+ levels. Instead, increased extracellular Calcium stabilizes sodium channels and **Raises the Threshold Potential** (makes it less negative, e.g., moves it from -65 to -55). By moving the threshold away from the depolarized RMP, Calcium restores the normal "distance" or safety margin between RMP and threshold, stabilizing the cardiac membrane (Membrane Stabilization). Therefore, the correct answer is b) It raises the Threshold Potential, antagonizing the membrane depolarization.

7. Which transport protein is primarily responsible for establishing the ion gradients (High Na+ out, High K+ in) that underlie excitability?

a) Na+ Leak Channel

b) Voltage-gated K+ channel

c) Na+-K+ ATPase

d) Na+-Ca2+ Exchanger

Explanation: While leak channels and the Nernst potential explain the voltage, the actual concentration gradients (High K+ inside, High Na+ outside) must be created and maintained against diffusion. This is the function of the **Na+-K+ ATPase** (Sodium-Potassium Pump). This primary active transporter consumes ATP to pump 3 Na+ out and 2 K+ in. Without this pump, the ion gradients would run down (dissipate), and the cell would lose its ability to generate electrical signals. It is the "battery charger" of the cell. Therefore, the correct answer is c) Na+-K+ ATPase.

8. The "Goldman-Hodgkin-Katz" equation differs from the Nernst equation because it:

a) Calculates the potential for a single ion only

b) Accounts for the permeability of multiple ions simultaneously

c) Assumes the membrane is impermeable to Chloride

d) Applies only to active transport

Explanation: The Nernst equation calculates the equilibrium potential for a single ion assuming ideal conditions. However, real membranes are permeable to several ions at once (Na, K, Cl). The **Goldman-Hodgkin-Katz (GHK) equation** calculates the actual membrane potential ($V_m$) by considering both the concentration gradients AND the relative **Permeability ($P$)** of all relevant ions. It is a weighted average. This explains why the RMP (-70 mV) is between $E_K$ (-90 mV) and $E_{Na}$ (+60 mV), but much closer to $E_K$ due to higher permeability. Therefore, the correct answer is b) Accounts for the permeability of multiple ions simultaneously.

9. Inhibitory Postsynaptic Potentials (IPSPs) in the central nervous system are often generated by the opening of channels for which ion?

a) Sodium

b) Calcium

c) Chloride

d) Magnesium

Explanation: Excitation (EPSP) involves depolarization (Na+ or Ca2+ influx). Inhibition (IPSP) involves hyperpolarization or stabilization of the membrane potential to prevent firing. This is achieved by opening channels for **Chloride (Cl-)** or Potassium (K+). GABA-A and Glycine receptors are Ligand-gated **Chloride channels**. When they open, Cl- flows into the cell (down its concentration gradient) or holds the potential at the Cl- equilibrium potential (~-70 mV), making it harder for the cell to reach threshold. This influx of negative charge produces the IPSP. Therefore, the correct answer is c) Chloride.

10. If the Na+-K+ pump is inhibited by Digoxin, what is the initial effect on the Resting Membrane Potential?

a) It immediately becomes 0 mV

b) It hyperpolarizes significantly

c) It depolarizes slightly (by a few mV)

d) It becomes equal to the Sodium equilibrium potential

Explanation: The Na+-K+ pump is electrogenic, pumping 3 Na+ out for 2 K+ in. This net loss of positive charge contributes directly to the RMP, adding about -4 mV to -5 mV of negativity. If the pump is acutely inhibited (e.g., by cardiac glycosides), this electrogenic contribution is lost immediately. Consequently, the RMP will **Depolarize slightly** (become less negative by a few millivolts). Over a longer period, as the concentration gradients run down (Na+ accumulates inside, K+ is lost), the depolarization will become profound, but the immediate effect is the loss of the electrogenic component. Therefore, the correct answer is c) It depolarizes slightly (by a few mV).

Chapter: General Physiology; Topic: Sensory System; Subtopic: Pain Pathways (Ascending Tracts)

Key Definitions & Concepts

• Nociception: The neural process of encoding noxious stimuli; the physiological perception of pain caused by tissue damage.

• Neospinothalamic Tract: The "Specific" pain pathway. Carries fast, sharp, well-localized pain (A-delta fibers). Projects to the VPL nucleus of the thalamus and then to the Somatosensory Cortex.

• Paleospinothalamic Tract: The "Non-specific" pain pathway. Carries slow, burning, aching, poorly localized pain (C-fibers). Projects to the Reticular Formation and Intralaminar nuclei of the thalamus.

• A-delta Fibers: Myelinated, fast-conducting fibers responsible for "First Pain" (sharp/pricking). Release Glutamate.

• C-Fibers: Unmyelinated, slow-conducting fibers responsible for "Second Pain" (dull/aching). Release Substance P and Glutamate.

• Substantia Gelatinosa (Lamina II): The "gatekeeper" area in the dorsal horn of the spinal cord where pain modulation occurs (Gate Control Theory).

• Lissauer’s Tract: The dorsolateral tract where pain fibers ascend or descend 1-2 segments before entering the dorsal horn.

• Anterolateral System: The collective name for the Spinothalamic, Spinoreticular, and Spinomesencephalic tracts carrying pain and temperature.

• VPL Nucleus (Ventral Posterolateral): The specific relay nucleus in the thalamus for body sensation (pain/temp/touch).

• Intralaminar Nuclei: Non-specific thalamic nuclei that project diffusely to the cortex and limbic system, mediating the emotional and arousal aspects of pain.

[Image of Pain pathways diagram]

Lead Question - 2016

Non-specific pain pathway is for?

a) Nociceptive pain

b) Neuropathic pain

c) Idiopathic pain

d) Inflammatory pain

Explanation: The ascending pain pathways are divided into the Neospinothalamic tract (Lateral/Specific) and the Paleospinothalamic tract (Medial/Non-specific). The Neospinothalamic tract carries "fast" sharp pain (A-delta fibers) directly to the specific sensory nuclei of the thalamus (VPL) for precise localization. The Paleospinothalamic tract carries "slow" burning or aching pain (C-fibers) and projects widely to the Reticular Formation and the Non-specific Intralaminar nuclei of the thalamus. This pathway is responsible for the arousal, emotional, and unpleasant aspects of pain. Both pathways are physiological systems designed to transmit signals arising from tissue damage, which is the definition of Nociceptive pain. Neuropathic pain is pathological damage to the nerve itself. Therefore, the correct answer is a) Nociceptive pain.

1. Which neurotransmitter is primarily released by A-delta fibers at their synapse in the dorsal horn to mediate fast pain?

a) Substance P

b) Glutamate

c) Glycine

d) Enkephalin

Explanation: Primary afferent nociceptors release excitatory neurotransmitters in the spinal cord. A-delta fibers, which are responsible for fast, sharp, and localized pain (first pain), primarily release Glutamate. Glutamate acts on AMPA and NMDA receptors to produce rapid synaptic transmission (milliseconds). In contrast, C-fibers (slow pain) release both Glutamate and the neuropeptide Substance P. Substance P is released more slowly and over a longer duration, contributing to the lingering, aching quality of slow pain. Glycine and Enkephalins are inhibitory transmitters involved in pain suppression. Therefore, the correct answer is b) Glutamate.

2. A patient experiences loss of pain and temperature sensation on the right side of the body below the level of the umbilicus. This indicates a lesion in the:

a) Right Dorsal Column

b) Left Lateral Spinothalamic Tract

c) Right Lateral Spinothalamic Tract

d) Left Dorsal Column

Explanation: The pathway for pain and temperature (Spinothalamic tract) decussates (crosses over) very early, usually within 1-2 segments of entry into the spinal cord, via the anterior white commissure. It then ascends in the Contralateral Lateral Funiculus. Therefore, a lesion of the spinothalamic tract causes loss of pain and temperature sensation on the Opposite (Contralateral) side of the body below the lesion. Since the patient has symptoms on the Right side, the lesion must be in the Left Lateral Spinothalamic Tract. Dorsal column lesions cause ipsilateral loss of vibration/proprioception. Therefore, the correct answer is b) Left Lateral Spinothalamic Tract.

3. The "Gate Control Theory" of pain proposes that non-painful stimuli (like rubbing a bumped shin) can inhibit pain transmission. This modulation occurs anatomically in the:

a) Thalamus

b) Somatosensory Cortex

c) Substantia Gelatinosa (Lamina II)

d) Reticular Formation

Explanation: The Gate Control Theory states that the transmission of pain signals through the dorsal horn of the spinal cord can be modulated by the simultaneous activation of large myelinated touch fibers (A-beta fibers). These A-beta fibers stimulate inhibitory interneurons (in the Substantia Gelatinosa of Rolando, Lamina II) that release Enkephalins/GABA. These inhibitory interneurons then presynaptically inhibit the incoming C-fibers and A-delta fibers, effectively "closing the gate" to pain transmission before it ascends to the brain. Therefore, the anatomical site is the Substantia Gelatinosa (Lamina II). Therefore, the correct answer is c) Substantia Gelatinosa (Lamina II).

4. The Paleospinothalamic tract (Slow Pain pathway) terminates primarily in which thalamic nuclei?

a) Ventral Posterolateral (VPL) Nucleus

b) Ventral Posteromedial (VPM) Nucleus

c) Intralaminar and Midline Nuclei

d) Lateral Geniculate Body

Explanation: The Spinothalamic system has two main projection targets. The Neospinothalamic tract (Fast pain) projects to the Ventrobasal complex (VPL and VPM), providing somatotopic localization ("My finger hurts"). The Paleospinothalamic tract (Slow pain) projects diffusely to the Reticular Formation of the brainstem and the Intralaminar (e.g., Centromedian) and Midline nuclei of the thalamus. These non-specific nuclei project widely to the cortex and limbic system, mediating the "suffering," alerting, and emotional aspects of pain ("I feel awful"), which are poorly localized. Therefore, the correct answer is c) Intralaminar and Midline Nuclei.

5. A 50-year-old male presents with severe, burning, intractable pain on the left side of his body following a stroke two months ago. Examination reveals raised threshold to pain but exaggerated response once perceived (Hyperpathia). This condition is known as:

a) Brown-Sequard Syndrome

b) Thalamic Pain Syndrome (Dejerine-Roussy)

c) Syringomyelia

d) Tabes Dorsalis

Explanation: This is the classic presentation of Thalamic Pain Syndrome (Dejerine-Roussy Syndrome). It typically results from a lacunar stroke involving the VPL/VPM nuclei of the thalamus (posterior cerebral artery territory). The initial anesthesia is followed weeks later by the development of severe, spontaneous, burning, or crushing pain (Central Neuropathic Pain) on the contralateral side. The pain is often exacerbated by light touch (Allodynia) or emotional stress and is notoriously difficult to treat. It represents a disinhibition of pain pathways or aberrant reorganization. Therefore, the correct answer is b) Thalamic Pain Syndrome (Dejerine-Roussy).

6. Which descending pathway is primarily responsible for the endogenous analgesia system (pain suppression)?

a) Corticospinal tract

b) Periaqueductal Gray (PAG) - Raphe Magnus pathway

c) Vestibulospinal tract

d) Rubrospinal tract

Explanation: The brain has a powerful descending system to inhibit pain entry at the spinal cord level. The key control center is the Periaqueductal Gray (PAG) matter in the midbrain. The PAG receives input from the hypothalamus and cortex. It projects to the Nucleus Raphe Magnus (in the medulla) and the Locus Coeruleus. Neurons from the Raphe Magnus (Serotonergic) and Locus Coeruleus (Noradrenergic) descend in the dorsolateral funiculus to the spinal cord dorsal horn, where they activate inhibitory interneurons (enkephalinergic) to block pain transmission. Therefore, the correct answer is b) Periaqueductal Gray (PAG) - Raphe Magnus pathway.

7. Visceral pain is often "referred" to somatic structures (e.g., cardiac pain to the left arm). The physiological basis for this Referred Pain is:

a) Convergence of somatic and visceral fibers on the same second-order neurons

b) Direct connection between the heart and the arm muscles

c) Misinterpretation by the peripheral receptors

d) Crossing over of fibers in the dorsal root ganglion

Explanation: Referred pain occurs because visceral pain fibers and somatic pain fibers (from the skin/muscles) enter the spinal cord at the same segment and Converge on the same Second-Order Neurons (Projection neurons) in the dorsal horn. Since the brain is accustomed to receiving signals from the skin (somatic) much more frequently than from the viscera, it "misinterprets" the signal coming from the shared neuron as originating from the corresponding dermatome. For example, heart afferents (T1-T5) converge with arm afferents (T1-T5), causing the brain to perceive the pain in the arm. Therefore, the correct answer is a) Convergence of somatic and visceral fibers on the same second-order neurons.

8. The tract of Lissauer (Dorsolateral fasciculus) serves which important function in the pain pathway?

a) It carries pain fibers directly to the brainstem

b) It allows pain fibers to ascend or descend 1-2 segments before entering the dorsal horn

c) It contains the cell bodies of the second-order neurons

d) It is the site of decussation

Explanation: When dorsal root fibers (A-delta and C) enter the spinal cord, they do not immediately penetrate the grey matter. Instead, they enter the Tract of Lissauer (Dorsolateral fasciculus) located at the tip of the dorsal horn. Here, the fibers bifurcate and ascend or descend for 1-2 spinal segments before synapsing on second-order neurons in the dorsal horn (Substantia Gelatinosa). This anatomical arrangement explains why a spinal cord lesion results in sensory loss that may begin 1-2 segments below the actual level of the lesion. Therefore, the correct answer is b) It allows pain fibers to ascend or descend 1-2 segments before entering the dorsal horn.

9. Anterolateral Cordotomy is a surgical procedure used for intractable pain relief. To relieve pain in the right leg, the surgeon must cut the:

a) Right Anterolateral quadrant

b) Left Anterolateral quadrant

c) Right Dorsal column

d) Left Dorsal column

Explanation: The Anterolateral system (Spinothalamic tract) carries pain and temperature information. Crucially, these fibers cross over (decussate) to the opposite side of the spinal cord almost immediately upon entry (within 1-2 segments). Therefore, pain signals from the Right leg ascend in the Left side of the spinal cord. To interrupt these signals and provide pain relief for the right leg, the surgeon must perform a cordotomy on the Left Anterolateral quadrant of the spinal cord (usually a few segments above the painful level to account for Lissauer's tract ascent). Therefore, the correct answer is b) Left Anterolateral quadrant.

10. Which receptor type is responsible for transduction of noxious heat (>45°C) and is activated by Capsaicin (from chili peppers)?

a) Piezo2

b) TRPM8

c) TRPV1

d) ASIC

Explanation: Nociceptors express specific ion channels that transduce noxious stimuli. The TRPV1 (Transient Receptor Potential Vanilloid 1) channel is the classic heat-sensing receptor. It opens in response to noxious heat (>43-45°C) and protons (acid). Crucially, it is also the specific receptor for Capsaicin, the active ingredient in hot chili peppers. Binding of capsaicin lowers the heat activation threshold to body temperature, creating the sensation of "burning" heat. TRPM8 detects cold/menthol. Piezo2 detects touch. ASIC detects acid. Therefore, the correct answer is c) TRPV1.

Chapter: General Physiology; Topic: Sensory System; Subtopic: Nerve Fiber Classification and Pain Transmission

Key Definitions & Concepts

• Erlanger-Gasser Classification: Classifies nerve fibers into A, B, and C types based on diameter, myelination, and conduction velocity.

• A-alpha (Aα) Fibers: The largest, fastest myelinated fibers; carry somatic motor signals and proprioception (muscle spindle).

• A-delta (Aδ) Fibers: Thinly myelinated fibers; responsible for "Fast Pain" (sharp, pricking, localized) and temperature (cold).

• C Fibers: The smallest, unmyelinated fibers with the slowest conduction velocity; responsible for "Slow Pain" (dull, aching, burning), diffuse visceral pain, and post-ganglionic autonomic signals.

• B Fibers: Medium-sized myelinated preganglionic autonomic fibers.

• Visceral Pain: Typically perceived as dull, aching, cramping, and poorly localized; transmitted almost exclusively by C fibers via the sympathetic/parasympathetic nerves.

• First Pain vs. Second Pain: First pain is sharp and immediate (A-delta); Second pain is delayed, burning, and longer-lasting (C fibers).

• Substance P: The primary neuropeptide neurotransmitter released by C fibers in the dorsal horn (along with glutamate).

• Paleospinothalamic Tract: The ascending pathway that primarily carries slow pain signals from C fibers to the brainstem and intralaminar nuclei.

• Susceptibility to Anesthesia: C fibers (small, unmyelinated) are generally the most susceptible to block by local anesthetics compared to large A fibers.

[Image of Nerve fiber classification diagram]

Lead Question - 2016

Dull visceral pain is carried by which type of neurons?

a) A gamma

b) Aa

c) C fibres

d) B

Explanation: Pain sensation is transmitted by two primary types of nerve fibers: A-delta and C fibers. A-delta fibers are myelinated and fast, carrying sharp, well-localized, "pricking" pain (cutaneous fast pain). C fibers are unmyelinated, thin, and slow-conducting. They carry dull, aching, burning, and poorly localized pain. Visceral pain is characteristically dull, deep, and cramping. The vast majority of afferents from the viscera are unmyelinated C fibers traveling with autonomic nerves. Therefore, the dull quality of visceral pain is encoded by these fibers. A-alpha are motor/proprioceptive. A-gamma are motor to muscle spindles. B fibers are preganglionic autonomic. Therefore, the correct answer is c) C fibres.

1. Which nerve fiber type has the slowest conduction velocity?

a) A-beta

b) A-delta

c) B fibers

d) C fibers

Explanation: Conduction velocity depends on axon diameter and myelination. Large, myelinated fibers conduct fastest (saltatory conduction). C fibers are unique because they are Unmyelinated and have the smallest diameter (0.5-2 micrometers). Consequently, they have the slowest conduction velocity (0.5-2 meters/sec). This slow speed accounts for the delay perceived in "second pain" (the throbbing ache that follows the initial sharp injury). All A fibers and B fibers are myelinated and faster. Therefore, the correct answer is d) C fibers.

2. Which sensory modality is primarily carried by A-beta fibers?

a) Sharp Pain

b) Temperature (Warmth)

c) Fine Touch and Vibration

d) Dull Aching Pain

Explanation: A-beta fibers are large, myelinated axons with fast conduction velocities (30-70 m/s). They are responsible for transmitting non-noxious cutaneous sensations such as Fine Touch, Vibration, and Pressure (from mechanoreceptors like Pacinian and Meissner corpuscles). These fibers ascend in the Dorsal Columns. Importantly, stimulating A-beta fibers (e.g., rubbing skin) can inhibit pain transmission from C fibers in the dorsal horn, forming the basis of the "Gate Control Theory" of pain relief. Therefore, the correct answer is c) Fine Touch and Vibration.

3. When a local anesthetic is applied to a nerve bundle, which fibers are typically blocked first?

a) Large myelinated motor fibers (A-alpha)

b) Small myelinated fibers (A-delta)

c) Small unmyelinated fibers (C fibers) and B fibers

d) Proprioceptive fibers

Explanation: Susceptibility to local anesthetic block is determined by size and myelination. Generally, smaller diameter fibers are blocked before larger ones because the anesthetic penetrates the axon more easily (surface area to volume ratio) and a shorter length of nerve needs to be affected to stop conduction in unmyelinated/short internode fibers. Therefore, the sequence of block is usually: Autonomic (B/C fibers) -> Pain/Temp (C and A-delta) -> Touch/Pressure (A-beta) -> Motor (A-alpha). Thus, C fibers (pain) are among the first to be blocked. Therefore, the correct answer is c) Small unmyelinated fibers (C fibers) and B fibers.

4. Muscle Spindles, which provide information about muscle length and stretch, are innervated by sensory fibers of type:

a) Ia and II

b) Ib

c) III (A-delta)

d) IV (C)

Explanation: In the numerical classification system (Lloyd-Hunt) used for sensory afferents from muscle: Type Ia fibers (primary endings) and Type II fibers (secondary endings) innervate Muscle Spindles. Type Ib fibers innervate Golgi Tendon Organs. Type III fibers correspond to A-delta (fast pain/cold). Type IV fibers correspond to C fibers (slow pain). The Ia fibers are the largest and fastest, crucial for the stretch reflex. Therefore, the correct answer is a) Ia and II.

5. Which nerve fiber type is responsible for the transmission of "First Pain" (sharp, localized)?

a) A-alpha

b) A-beta

c) A-delta

d) C fibers

Explanation: When you accidentally touch a hot stove, you feel two distinct waves of pain. The first is an immediate, sharp, well-localized "ouch" sensation. This is First Pain (or fast pain), carried by A-delta fibers (Group III). These are thinly myelinated and conduct at 6-30 m/s. Following this is a delayed, dull, burning ache ("Second Pain"), carried by slower, unmyelinated C fibers (0.5-2 m/s). This dual transmission serves first to withdraw (reflex) and then to protect/heal (ache). Therefore, the correct answer is c) A-delta.

6. Which fibers are most susceptible to block by hypoxia (pressure)?

a) A-fibers (Large myelinated)

b) B-fibers

c) C-fibers (Unmyelinated)

d) All are equally susceptible

Explanation: Different stressors block nerve fibers in different orders. Hypoxia (Pressure/Compression): Affects Large Myelinated (A fibers) first. This is why your leg "falls asleep" (numbness/motor loss) when crossed for too long, but you might still feel a dull ache later. Local Anesthetics: Affect Small fibers (C fibers) first. Temperature (Cold): Affects myelinated fibers before unmyelinated, but intermediate sizes often blocked early. Mnemonic: "HAL" - Hypoxia blocks A-fibers (Large). Therefore, the correct answer is a) A-fibers (Large myelinated).

7. Preganglionic autonomic neurons fall under which Erlanger-Gasser classification?

a) A-gamma

b) B fibers

c) C fibers

d) A-delta

Explanation: The Erlanger-Gasser classification is: A: Somatic motor and sensory (alpha, beta, gamma, delta). B: Preganglionic Autonomic (sympathetic/parasympathetic). These are lightly myelinated, medium diameter (3-15 m/s). C: Postganglionic Autonomic (motor) and Slow Pain (sensory). These are unmyelinated. A-gamma fibers are motor to muscle spindles (intrafusal fibers). Therefore, the correct answer is b) B fibers.

8. The neurotransmitter "Substance P" is most closely associated with the synaptic transmission of:

a) Fine touch

b) Vibration

c) Slow, chronic pain

d) Fast, sharp pain

Explanation: Nociceptive C-fibers release excitatory neurotransmitters at their synapse in the spinal cord (Substantia Gelatinosa). While Glutamate is released for rapid signaling, C-fibers also co-release the neuropeptide Substance P. Substance P acts on NK-1 receptors. It is released slowly and its effects are prolonged, contributing to the temporal summation and the lasting, aching quality of Slow, chronic pain. A-delta fibers (fast pain) release primarily Glutamate. Therefore, the correct answer is c) Slow, chronic pain.

9. A-gamma (γ) motor neurons innervate:

a) Extrafusal muscle fibers (Skeletal muscle)

b) Intrafusal muscle fibers (Muscle Spindle)

c) Smooth muscle

d) Golgi tendon organs

Explanation: The motor output to muscle is divided into Alpha and Gamma systems. A-alpha motor neurons: Innervate the main force-generating muscle fibers (Extrafusal fibers). A-gamma motor neurons: Innervate the specialized muscle fibers inside the Muscle Spindle (Intrafusal fibers). Activation of gamma motor neurons contracts the ends of the spindle, keeping it taut and sensitive to stretch even when the main muscle shortens (Alpha-Gamma Coactivation). Therefore, the correct answer is b) Intrafusal muscle fibers (Muscle Spindle).

10. Which fiber type corresponds to Group IV in the numerical (Lloyd-Hunt) classification?

a) A-alpha

b) A-beta

c) A-delta

d) C fibers

Explanation: There are two classifications: Letter (Erlanger-Gasser) for all nerves, and Number (Lloyd-Hunt) specifically for sensory nerves from muscle. Group I (Ia/Ib) = A-alpha (largest). Group II = A-beta. Group III = A-delta. Group IV = C fibers (unmyelinated). Knowing the equivalence is important as questions may use either terminology interchangeably. Group IV fibers typically carry pain (nociception) from muscles. Therefore, the correct answer is d) C fibers.

Chapter: General Physiology; Topic: Sensory System; Subtopic: Ascending Tracts and Sensory Transmission

Key Definitions & Concepts

• C Fibers: Small, unmyelinated nerve fibers with slow conduction velocity (0.5–2 m/s). They are responsible for transmitting slow (burning) pain, temperature (warmth), and crude touch.

• Lateral Spinothalamic Tract (LSTT): The ascending pathway in the lateral white column of the spinal cord that carries pain and temperature sensations to the thalamus.

• Anterior Spinothalamic Tract (ASTT): The ascending pathway in the anterior white column that carries crude touch and pressure sensations.

• Posterior Column-Medial Lemniscus Pathway (PCML): The pathway responsible for fine touch, vibration, and proprioception; consists of large, myelinated A-beta fibers.

• Substantia Gelatinosa: Located in Lamina II of the dorsal horn; the primary site where C fibers synapse and where pain modulation (Gate Control) occurs.

• Substance P: A neuropeptide neurotransmitter released by C fibers involved in the transmission of slow pain and neurogenic inflammation.

• Paleospinothalamic Pathway: The phylogenetically older division of the pain system (C fibers) that projects to the reticular formation and intralaminar nuclei, mediating the emotional aspect of pain.

• Neospinothalamic Pathway: The newer division (A-delta fibers) projecting to the VPL nucleus, mediating the localization of sharp pain.

• Decussation: The crossing over of nerve fibers to the opposite side. Spinothalamic fibers decussate in the spinal cord (anterior white commissure), whereas PCML fibers decussate in the medulla.

• Lissauer's Tract: The dorsolateral tract where primary afferent fibers may ascend or descend 1-2 segments before entering the dorsal horn gray matter.

[Image of Pain pathways diagram]

Lead Question - 2016

'C' fibers carry sensations through which pathway?

a) Posterior column

b) Anterior spinothalamic tract

c) Lateral spinothalamic tract

d) All of the above

Explanation: Nerve fibers are classified based on myelination and diameter. 'C' fibers are unmyelinated, small-diameter fibers responsible for transmitting Slow Pain (aching/burning) and Temperature sensations. These modalities are carried centrally by the Lateral Spinothalamic Tract. The Anterior Spinothalamic Tract carries crude touch and pressure (which also utilizes C and A-delta fibers, but the classic association for "sensation" regarding C fibers in isolation is pain/temperature). The Posterior Column carries fine touch and proprioception via large A-beta fibers. Therefore, the specific pathway for the hallmark sensations of C fibers (pain/temp) is the lateral tract. Therefore, the correct answer is c) Lateral spinothalamic tract.

1. A patient presents with a cape-like distribution of loss of pain and temperature sensation across the shoulders and arms. Proprioception is preserved. This "Dissociated Sensory Loss" is characteristic of a lesion affecting the:

a) Dorsal Root Ganglia

b) Anterior White Commissure

c) Posterior Columns

d) Corticospinal Tract

Explanation: This clinical picture describes Syringomyelia, a condition where a cystic cavity (syrinx) forms in the central canal of the spinal cord. As the cyst expands, it compresses the Anterior White Commissure. This is the anatomical location where the second-order neurons of the Spinothalamic tract (carrying pain and temperature) decussate (cross over) to the opposite side. Compression here interrupts these crossing fibers bilaterally at the level of the lesion, causing segmental loss of pain and temperature. The dorsal columns (proprioception) located posteriorly are typically spared. Therefore, the correct answer is b) Anterior White Commissure.

2. Which neurotransmitter is the primary agent responsible for the slow, prolonged synaptic transmission of pain signals from C fibers in the dorsal horn?

a) Glutamate

b) Glycine

c) Substance P

d) Acetylcholine

Explanation: C fibers release excitatory neurotransmitters to activate second-order neurons. They release Glutamate (acting on AMPA/NMDA receptors) for rapid signaling, but uniquely, they also co-release the neuropeptide Substance P. Substance P acts on NK-1 receptors. It has a slow onset and a long duration of action, allowing for the temporal summation of signals. This prolonged depolarization contributes to the characteristically "dull, aching, and persistent" nature of slow pain carried by C fibers. A-delta fibers release primarily Glutamate. Therefore, the correct answer is c) Substance P.

3. In the Brown-Sequard syndrome (hemisection of the spinal cord), which sensory deficit is observed on the CONTRA-lateral side below the level of the lesion?

a) Loss of vibration sense

b) Loss of fine touch

c) Loss of pain and temperature

d) Loss of proprioception

Explanation: In a spinal cord hemisection, tracts traveling on one side are cut. The Dorsal Columns (proprioception/vibration) ascend ipsilaterally and cross in the medulla; thus, damage causes ipsilateral loss. The Corticospinal tract (motor) is also crossed above; thus, damage causes ipsilateral paralysis. However, the Lateral Spinothalamic Tract (pain/temperature) contains fibers that have already crossed (decussated) at the spinal level below. Therefore, cutting the right side of the cord interrupts pain signals coming from the Left (Contralateral) side of the body. Therefore, the correct answer is c) Loss of pain and temperature.

4. The Paleospinothalamic pathway, which carries slow pain info via C fibers, projects primarily to which non-specific nuclei to mediate arousal and emotion?

a) Ventral Posterolateral (VPL) nucleus

b) Medial Geniculate Body

c) Intralaminar nuclei of Thalamus

d) Ventral Anterior nucleus

Explanation: The pain system has two main projection targets. The Neospinothalamic tract (fast pain) goes to the VPL nucleus for localization. The Paleospinothalamic tract (slow pain/C fibers) has a more diffuse termination. It projects to the Reticular Formation (for alertness) and the Intralaminar Nuclei (e.g., Centromedian) of the thalamus. These nuclei project diffusely to the cortex and limbic system, generating the emotional, unpleasant, and alerting responses ("suffering") associated with chronic pain, rather than precise localization. Therefore, the correct answer is c) Intralaminar nuclei of Thalamus.

5. A neurosurgeon performs a Cordotomy to relieve intractable pain in a cancer patient's right leg. To achieve this, the surgeon must interrupt the spinothalamic tract in the:

a) Right dorsal column

b) Left anterolateral quadrant

c) Right anterolateral quadrant

d) Left posterior horn

Explanation: The lateral spinothalamic tract carries pain information from the contralateral side of the body because fibers cross the midline shortly after entering the cord. Therefore, pain signals from the Right leg ascend in the Left side of the spinal cord (specifically the anterolateral quadrant). To relieve pain in the right leg, the surgeon must cut the Left Anterolateral Quadrant. The cut is usually made a few segments higher than the pain level to account for the ascent of fibers in Lissauer's tract before crossing. Therefore, the correct answer is b) Left anterolateral quadrant.

6. C fibers terminate primarily in which specific lamina of the dorsal horn?

a) Lamina I (Marginal Nucleus)

b) Lamina II (Substantia Gelatinosa)

c) Lamina III and IV (Nucleus Proprius)

d) Lamina IX (Motor pools)

Explanation: The gray matter of the spinal cord is divided into Rexed Laminae. Pain fibers have specific termination sites. A-delta fibers (fast pain) terminate largely in Lamina I (Marginal Zone) and Lamina V. C fibers (slow pain) terminate almost exclusively in Lamina II, also known as the Substantia Gelatinosa. This area is rich in interneurons and opioids and is the key anatomical site for the "Gate Control" modulation of pain transmission. Therefore, the correct answer is b) Lamina II (Substantia Gelatinosa).

7. Which sensory modality is NOT carried by the Anterolateral System (Spinothalamic tracts)?

a) Thermal sensation

b) Vibration

c) Crude touch

d) Pain

Explanation: The sensory systems are broadly divided into two pathways. The Anterolateral System (Anterior + Lateral Spinothalamic) carries Pain, Temperature, Crude touch, pressure, tickle, and itch. The Posterior Column-Medial Lemniscus (PCML) pathway carries Fine (discriminative) touch, Vibration, and Proprioception (joint position sense). Therefore, Vibration is the specific modality that does NOT travel in the Anterolateral system; it travels in the dorsal columns. This distinction is vital for localizing spinal cord lesions. Therefore, the correct answer is b) Vibration.

8. A patient with a stroke in the posterior cerebral artery territory develops "Thalamic Pain Syndrome" (Dejerine-Roussy). This involves a lesion of the VPL nucleus, which is the relay station for:

a) Spinothalamic tract only

b) Medial Lemniscus only

c) Both Spinothalamic tract and Medial Lemniscus

d) Trigeminal lemniscus

Explanation: The Ventral Posterolateral (VPL) nucleus of the thalamus is the master relay station for all somatosensory information from the body (neck down). It receives input from Both the Spinothalamic tract (Pain/Temp/Crude touch) and the Medial Lemniscus (Fine touch/Vibration/Proprioception). A lesion here causes complete hemianesthesia (loss of all sensation) on the contralateral side of the body. Recovery can be complicated by the development of excruciating central neuropathic pain. Therefore, the correct answer is c) Both Spinothalamic tract and Medial Lemniscus.

9. Lateral Medullary Syndrome (Wallenberg Syndrome) results in loss of pain and temperature on the ipsilateral face and contralateral body. The body sensory loss is due to damage to the:

a) Medial Lemniscus

b) Lateral Spinothalamic Tract

c) Spinal Nucleus of Trigeminal

d) Nucleus Gracilis

Explanation: In the lateral medulla, the Lateral Spinothalamic Tract (carrying pain/temp from the contralateral body) ascends located peripherally. A PICA infarct damages this tract, causing loss of pain/temp on the Contralateral Body. Simultaneously, the infarct damages the Spinal Nucleus/Tract of Trigeminal (carrying pain/temp from the ipsilateral face), causing loss of sensation on the Ipsilateral Face. This "crossed" sensory loss is the hallmark of Wallenberg syndrome. The Medial Lemniscus is medial and spared. Therefore, the correct answer is b) Lateral Spinothalamic Tract.

10. Unlike the Dorsal Column pathway, the first-order neurons of the Spinothalamic pathway:

a) Synapse immediately in the dorsal horn

b) Ascend all the way to the medulla before synapsing

c) Are multipolar neurons

d) Cross the midline in the dorsal root ganglion

Explanation: There is a fundamental difference in the trajectory of the first-order neuron. In the Dorsal Column system, the primary axon enters the cord and ascends ipsilaterally all the way to the medulla before synapsing. In the Spinothalamic system, the first-order neuron enters the cord and Synapses immediately (or within 1-2 segments via Lissauer's tract) on a second-order neuron in the dorsal horn. It is the second-order neuron that decussates and ascends. Both have cell bodies in the DRG (pseudounipolar). Therefore, the correct answer is a) Synapse immediately in the dorsal horn.

Chapter: General Physiology; Topic: Nerve-Muscle Physiology; Subtopic: Classification of Nerve Fibers

Key Definitions & Concepts

• Erlanger-Gasser Classification: Classifies peripheral nerve fibers into A, B, and C groups based on diameter, myelination, and conduction velocity.

• C Fibers: The smallest nerve fibers (0.5-2 micrometers) and the only group that is Unmyelinated. They conduct impulses slowly (0.5-2 m/s).

• Sensory Function of C Fibers: They carry "Slow Pain" (dull, aching, burning), temperature (warmth), crude touch, and itch from the periphery to the dorsal horn (Dorsal Root C fibers).

• Motor Function of C Fibers: They constitute the postganglionic autonomic fibers (Sympathetic and Parasympathetic) supplying smooth muscle, cardiac muscle, and glands.

• A-Fibers: Large, myelinated fibers subdivided into alpha, beta, gamma, and delta. Responsible for somatic motor and fast sensory functions.

• B-Fibers: Medium-sized, lightly myelinated fibers. They are exclusively Preganglionic Autonomic fibers.

• Remak Bundles: The unique histological arrangement where multiple unmyelinated C fiber axons are enveloped by a single Schwann cell without forming myelin sheaths.

• Susceptibility: C fibers are most susceptible to block by local anesthetics but least susceptible to block by pressure/hypoxia.

• Polymodal Nociceptors: C fiber terminals that respond to multiple types of noxious stimuli (mechanical, thermal, and chemical).

• Group IV Fibers: The equivalent term for C fibers in the Lloyd-Hunt numerical classification used for muscle afferents.

[Image of Nerve fiber classification diagram]

Lead Question - 2016

Types C nerve fibers are?

a) Sensory

b) Motor

c) Mixed

d) Any of the above

Explanation: The classification of C fibers includes two distinct functional groups. First, the Dorsal Root C fibers are sensory afferents responsible for transmitting slow pain, temperature, and crude touch. Second, the Sympathetic C fibers represent the postganglionic autonomic efferents (motor) supplying viscera, vessels, and glands. Therefore, anatomically and functionally, the category "Type C fibers" encompasses both sensory (afferent) and motor (autonomic efferent) neurons. Consequently, the correct description for the group as a whole is that they can be either sensory or motor depending on the specific nerve. Therefore, the correct answer is d) Any of the above (or functionally "Mixed" in the context of the whole body's population, but 'Any of the above' covers the fact that individual C fibers can be sensory OR motor).

1. Which physiological feature is unique to Type C nerve fibers compared to Type A and Type B fibers?

a) They have the largest diameter

b) They are unmyelinated

c) They are exclusively motor

d) They have the fastest conduction velocity

Explanation: The defining structural characteristic of Type C fibers in the Erlanger-Gasser classification is that they are Unmyelinated. Both Type A (somatic motor/sensory) and Type B (preganglionic autonomic) fibers possess a myelin sheath, which allows for faster saltatory conduction. C fibers lack this sheath; instead, multiple axons are embedded in the cytoplasm of a Schwann cell (Remak bundle), leading to continuous, slow conduction (0.5 to 2.0 m/s). This lack of myelin explains their slow transmission of "second pain." Therefore, the correct answer is b) They are unmyelinated.

2. Which sensory modality is primarily transmitted by C fibers?

a) Proprioception

b) Fine touch and vibration

c) Slow, burning pain

d) Fast, sharp pain

Explanation: Sensory information is segregated by fiber type. Proprioception travels on the fastest fibers (A-alpha, A-beta). Fine touch and vibration travel on A-beta fibers. Fast, sharp ("first") pain travels on A-delta fibers. C fibers, due to their slow conduction speed, transmit sensations that have a delayed onset or prolonged duration, specifically Slow, burning, aching pain ("second pain"), warmth, and itch (pruritus). This is why a stubbed toe hurts sharply first (A-delta), followed by a throbbing ache (C fiber). Therefore, the correct answer is c) Slow, burning pain.

3. In the autonomic nervous system, postganglionic sympathetic neurons are classified as:

a) Type A-gamma fibers

b) Type B fibers

c) Type C fibers

d) Type A-delta fibers

Explanation: The autonomic pathway consists of a two-neuron chain. The Preganglionic neuron (from CNS to ganglion) is a myelinated Type B fiber. The Postganglionic neuron (from ganglion to effector organ) is an unmyelinated Type C fiber. This applies to both the sympathetic and parasympathetic divisions (though parasympathetic postganglionic fibers are very short). Thus, the "motor" component of C fibers refers to these autonomic efferents regulating smooth muscle and glands. Therefore, the correct answer is c) Type C fibers.

4. When comparing susceptibility to nerve block, C fibers are the MOST susceptible to:

a) Hypoxia

b) Pressure

c) Local Anesthetics

d) Electrical stimulation

Explanation: Local anesthetics (like Lidocaine) block sodium channels. They penetrate small, unmyelinated fibers much more easily than large, myelinated ones (due to surface area/volume ratios and the need to block usually 3 nodes of Ranvier in myelinated fibers). Therefore, C fibers (pain/autonomic) are blocked first by Local Anesthetics. Conversely, they are the least susceptible to pressure/hypoxia, which preferentially blocks large A fibers first (causing limbs to "fall asleep" with loss of touch/motor but preservation of slow pain). Therefore, the correct answer is c) Local Anesthetics.

5. Which neurotransmitter is characteristically co-released with Glutamate by nociceptive C fibers in the spinal cord?

a) Acetylcholine

b) Substance P

c) Glycine

d) Norepinephrine

Explanation: C fibers involved in pain transmission release excitatory neurotransmitters at their synapse in the dorsal horn (substantia gelatinosa). While Glutamate mediates rapid transmission, C fibers uniquely release neuropeptides, most notably Substance P (and CGRP). Substance P binds to NK-1 receptors and mediates slow, prolonged synaptic potentials, contributing to the "wind-up" phenomenon and the lasting nature of slow pain. A-delta fibers rely mostly on Glutamate. Therefore, the correct answer is b) Substance P.

6. According to the Lloyd-Hunt numerical classification of sensory nerve fibers, Group IV fibers are equivalent to:

a) A-alpha fibers

b) A-beta fibers

c) A-delta fibers

d) C fibers

Explanation: The numerical classification (Group I-IV) is used primarily for muscle afferents. Group Ia/Ib = A-alpha (Primary spindle/GTO). Group II = A-beta (Secondary spindle/Touch). Group III = A-delta (Fast pain/Cold). Group IV = C fibers (Slow pain/Temperature). Knowing these equivalents is crucial as physiology questions often interchange the terminology. Group IV fibers are the unmyelinated free nerve endings in muscle and joints responding to noxious stimuli. Therefore, the correct answer is d) C fibers.

7. The "Triple Response of Lewis" (Red reaction, Flare, Wheal) is mediated in part by the antidromic release of substances from which nerve fibers?

a) Sympathetic postganglionic fibers

b) Sensory C fibers

c) Motor A-alpha fibers

d) Parasympathetic fibers

Explanation: When skin is injured, the "Flare" component (redness spreading beyond the injury site) is caused by an Axon Reflex. Impulses travel up sensory C fibers and then travel "backwards" (antidromically) down other branches of the same nerve fiber supplying adjacent skin. This triggers the release of vasoactive neuropeptides like Substance P and CGRP from the nerve terminals, causing vasodilation and mast cell degranulation (histamine release). This neurogenic inflammation is a specific function of peptidergic C fibers. Therefore, the correct answer is b) Sensory C fibers.

8. Which of the following values represents the typical conduction velocity range for C fibers?

a) 70-120 m/s

b) 30-70 m/s

c) 3-15 m/s

d) 0.5-2.0 m/s

Explanation: Conduction velocities are strictly stratified. A-alpha: 70-120 m/s (fastest). A-beta: 30-70 m/s. A-gamma: 15-30 m/s. A-delta: 6-30 m/s. B fibers: 3-15 m/s. C fibers: 0.5-2.0 m/s (slowest). Because they are unmyelinated, they rely on continuous conduction, which is significantly slower than saltatory conduction. This velocity is roughly equivalent to walking speed. Therefore, the correct answer is d) 0.5-2.0 m/s.

9. A-delta fibers differ from C fibers in that A-delta fibers:

a) Are unmyelinated

b) Carry visceral pain primarily

c) Have a higher threshold for activation

d) Conduct impulses faster due to thin myelination

Explanation: A-delta and C fibers are both nociceptors, but they have key structural differences. A-delta fibers are thinly myelinated, whereas C fibers are unmyelinated. This myelination allows A-delta fibers to conduct impulses faster (6-30 m/s vs 0.5-2 m/s). This speed difference is the physiological basis for the "double pain" sensation (sharp first, aching second). A-delta fibers are responsible for the initial, localizing withdrawal reflex. Visceral pain is predominantly C fiber mediated. Therefore, the correct answer is d) Conduct impulses faster due to thin myelination.

10. The receptor type most commonly found on the terminal ends of C fibers that responds to noxious heat (>43°C) and Capsaicin is:

a) Piezo2

b) TRPV1

c) Merkel disc

d) Meissner corpuscle

Explanation: The molecular transducer for heat pain located on C fibers (and some A-delta fibers) is the TRPV1 (Transient Receptor Potential Vanilloid 1) channel. This ion channel opens in response to damaging heat, low pH (acid), and Capsaicin (the hot compound in chili peppers). Activation of TRPV1 leads to the influx of Calcium and Sodium, depolarizing the C fiber and generating the sensation of burning pain. Piezo2 is for touch; Meissner/Merkel are touch receptors on A-beta fibers. Therefore, the correct answer is b) TRPV1.

Chapter: General Physiology; Topic: Sensory System; Subtopic: Thermal Sensation and Nerve Fibers

Key Definitions & Concepts

• Thermoreceptors: Free nerve endings located in the skin that detect changes in temperature; divided into cold and warmth receptors.

• Cold Receptors: The most numerous thermoreceptors; stimulated by temperatures between 10°C and 40°C. Signals are transmitted primarily by A-delta fibers (and some C fibers).

• Warmth Receptors: Less numerous than cold receptors; stimulated by temperatures between 30°C and 49°C. Signals are transmitted almost exclusively by C fibers.

• A-delta Fibers (Type III): Thinly myelinated, fast-conducting fibers responsible for "Fast Pain" (sharp) and "Cold" sensation.

• C Fibers (Type IV): Unmyelinated, slow-conducting fibers responsible for "Slow Pain" (aching), "Warmth," and itch.

• Paradoxical Cold: The sensation of cold perceived when a cold receptor is stimulated by a noxious heat stimulus (above 45°C).

• TRP Channels: Transient Receptor Potential channels on nerve endings that act as molecular thermometers (e.g., TRPM8 for cold/menthol, TRPV1 for heat/capsaicin).

• Lateral Spinothalamic Tract: The ascending pathway in the spinal cord carrying pain and temperature sensations to the thalamus.

• Adaptation: Thermoreceptors show rapid adaptation; they respond vigorously to changes in temperature but decrease firing during constant temperature.

• Spatial Summation: The ability to detect weak thermal stimuli increases significantly when a larger area of skin is stimulated.

[Image of Nerve fiber classification diagram]

Lead Question - 2016

Warmth sensation is carried by?

a) A alpha fibers

b) A beta fibers

c) A gamma fibers

d) A delta fibers

Explanation: Thermal sensations are transmitted by specific nerve fibers. Warmth sensation is transmitted mainly by unmyelinated Type C fibers at transmission velocities of 0.4 to 2 m/s. Cold sensation is transmitted mainly by Type A-delta fibers (thinly myelinated) and to a lesser extent by Type C fibers. In the provided options, "A S" likely represents A-delta (due to OCR error), and "A (3" represents A-beta. Since Warmth is physiologically carried by C fibers (which are not listed as a clear option here, but are the correct physiological answer), one must differentiate carefully. If the question implies thermal sensation in general or "Cold," A-delta is the answer. However, for "Warmth" specifically, the strict answer is C fibers. (Note: In exams, if C is absent and A-delta is the only thermal fiber listed, it is sometimes chosen by exclusion, but C is the correct physiology). Therefore, the correct physiological answer is C fibers.

1. Which specific TRP ion channel is activated by innocuous cold temperatures (10-25°C) and cooling agents like Menthol?

a) TRPV1

b) TRPM8

c) TRPV3

d) TRPA1

Explanation: Thermoreception is mediated by Transient Receptor Potential (TRP) channels. TRPM8 (Melastatin 8) is the primary cold-sensing receptor. It opens in response to cooling temperatures (below 25°C) and chemical agents like Menthol (from mint) and Eucalyptol, producing a sensation of cold. TRPV1 responds to noxious heat (>43°C) and Capsaicin. TRPV3/TRPV4 respond to warm temperatures. TRPA1 responds to noxious cold and irritants (mustard oil). Therefore, the correct answer is b) TRPM8.

2. The sensation of "Paradoxical Cold" occurs when a cold receptor is stimulated by:

a) Extreme cold (< 0°C)

b) Hot stimulus (> 45°C)

c) Mechanical pressure

d) Chemical irritants

Explanation: Paradoxical cold is a physiological curiosity where a heat stimulus produces a sensation of cold. This occurs because Cold Receptors (A-delta fibers) can be stimulated not only by low temperatures but also by high, noxious temperatures (typically > 45°C). Because the "labeled line" for that nerve fiber communicates "cold" to the brain, the brain interprets this high-heat activation as "cold." This is often experienced when entering a very hot bath. Therefore, the correct answer is b) Hot stimulus (> 45°C).

3. Which type of nerve fiber is primarily responsible for transmitting signals from Cold Receptors?

a) A-alpha

b) A-beta

c) A-delta

d) B fibers

Explanation: There is a distinct difference in the transmission of cold vs. warmth. Cold signals are transmitted primarily by A-delta fibers (thinly myelinated, conduction velocity ~20 m/s). Some cold signals are also carried by C fibers. In contrast, warmth signals are carried almost exclusively by C fibers. This explains why the sensation of cold is perceived relatively quickly compared to the slower, building sensation of warmth. Therefore, the correct answer is c) A-delta.

4. Thermal sensations (both pain and temperature) ascend the spinal cord via which tract?

a) Dorsal Column Medial Lemniscus

b) Lateral Spinothalamic Tract

c) Anterior Spinothalamic Tract

d) Spinocerebellar Tract

Explanation: The Anterolateral System is responsible for pain and temperature. Specifically, the Lateral Spinothalamic Tract carries fibers for Pain and Temperature. These fibers enter the spinal cord, synapse in the dorsal horn, and cross (decussate) to the contralateral side via the anterior white commissure before ascending. The Anterior Spinothalamic tract carries crude touch and pressure. The Dorsal Columns carry fine touch and proprioception. Therefore, the correct answer is b) Lateral Spinothalamic Tract.

5. A lesion of the Lateral Spinothalamic tract on the right side of the spinal cord at T10 would result in loss of thermal sensation on the:

a) Right leg

b) Left leg

c) Right arm

d) Left arm

Explanation: Because the fibers carrying pain and temperature decussate (cross over) almost immediately upon entering the spinal cord (within 1-2 segments), the Lateral Spinothalamic Tract on one side carries information from the Opposite (Contralateral) side of the body. A lesion on the Right side at T10 would block signals ascending from the Left side below that level. Thus, the patient would lose temperature sensation in the Left leg. Therefore, the correct answer is b) Left leg.

6. At what temperature range do pain receptors (nociceptors) begin to be stimulated by heat, eliciting the sensation of burning pain?

a) > 30°C

b) > 37°C

c) > 45°C

d) > 60°C

Explanation: Thermal receptors function within specific ranges. Warmth receptors are active from roughly 30°C to 45°C. As the temperature rises above 45°C, the warmth receptors stop firing or are saturated, and the heat begins to cause tissue damage. At this point (>45°C), Pain receptors (polymodal nociceptors stimulating TRPV1 channels) are activated, and the sensation changes from "warm/hot" to "burning pain." Cold pain typically begins below 10-15°C. Therefore, the correct answer is c) > 45°C.

7. Which receptor is the molecular target for Capsaicin (the active component of chili peppers) and is responsible for the sensation of spicy heat?

a) TRPM8

b) TRPV1

c) TRPA1

d) Piezo2

Explanation: TRPV1 (Transient Receptor Potential Vanilloid 1) is a non-selective cation channel located on nociceptive nerve endings (C and A-delta fibers). It is activated by noxious heat (>43°C) and low pH (acid). Crucially, it is also activated by Capsaicin. When capsaicin binds to TRPV1, it lowers the channel's activation threshold to below body temperature, causing it to open at normal body heat. This results in the brain perceiving a sensation of "burning hot" despite no actual temperature rise. Therefore, the correct answer is b) TRPV1.

8. Compared to cold receptors, warmth receptors are:

a) More numerous

b) Less numerous

c) Equal in number

d) Found only in the viscera

Explanation: Mapping of thermal spots on the skin reveals a significant disparity in density. Cold receptors are far more numerous than warmth receptors. In most areas of the body, there are 3 to 10 times as many cold spots as warm spots. This evolutionary adaptation likely reflects the greater environmental threat posed by hypothermia compared to mild hyperthermia. Both receptors are free nerve endings found in the skin. Therefore, the correct answer is b) Less numerous.

9. Spatial summation is a critical feature of thermal sensation. This means that:

a) Temperature sensation persists after the stimulus is removed

b) Rapid changes in temperature are felt more intensely

c) Small changes in temperature are detected if a large area of skin is stimulated

d) Thermal signals summate with pain signals

Explanation: Thermal receptors (especially warmth) show strong Spatial Summation. While a tiny change in temperature (e.g., 0.01°C) applied to a single spot might not be felt, the same tiny change applied over a large body surface area (like the entire trunk) is easily detected. This allows the body to monitor total body heat load very precisely. This summation occurs centrally in the spinal cord and brainstem. Temporal adaptation is also a feature (feeling the bath water cool down over time). Therefore, the correct answer is c) Small changes in temperature are detected if a large area of skin is stimulated.

10. The cell bodies of the primary afferent neurons carrying temperature sensation from the body are located in the:

a) Dorsal Horn of Spinal Cord

b) Dorsal Root Ganglion

c) Ventral Posterior Nucleus of Thalamus

d) Sympathetic Chain Ganglion

Explanation: All primary somatic sensory neurons (for touch, pain, temperature, proprioception) have their cell bodies located in the Dorsal Root Ganglion (DRG) (for the body) or the Trigeminal Ganglion (for the face). These are pseudounipolar neurons. The peripheral process extends to the skin (free nerve ending), and the central process enters the spinal cord to synapse in the dorsal horn (Substantia Gelatinosa). The dorsal horn contains the second-order neuron bodies. Therefore, the correct answer is b) Dorsal Root Ganglion.

Chapter: General Physiology; Topic: Nerve-Muscle Physiology; Subtopic: Contractile and Regulatory Proteins of Muscle

Key Definitions & Concepts

• Myosin: The contractile protein that forms the Thick Filaments. It is a molecular motor that converts chemical energy (ATP) into mechanical force.

• Actin: The globular protein (G-actin) that polymerizes to form the double-helical Thin Filaments (F-actin). It contains the binding sites for myosin.

• ATPase Activity: A localized enzymatic function on the Myosin Head (S1 fragment) that hydrolyzes ATP into ADP and inorganic phosphate (Pi) to energize the cross-bridge.

• Tropomyosin: A regulatory filamentous protein that lies in the groove of the actin helix, covering the myosin-binding sites in the resting state.

• Troponin Complex: A heterotrimer consisting of Troponin T (binds Tropomyosin), Troponin I (Inhibits binding), and Troponin C (binds Calcium).

• Cross-Bridge Cycle: The cyclical attachment, power stroke, detachment, and re-cocking of myosin heads interacting with actin.

• Power Stroke: The conformational change where the myosin head pivots, pulling the actin filament toward the center of the sarcomere (M-line); triggered by the release of Phosphate.

• ATP Binding: Essential for the detachment of the myosin head from the actin filament after the power stroke.

• Titin: A giant elastic protein connecting the Z-disk to the M-line, maintaining the alignment of the thick filament.

• Sliding Filament Theory: Muscle contraction occurs by the sliding of thin filaments over thick filaments, shortening the sarcomere without changing filament length.

[Image of Myosin molecule structure]

Lead Question - 2016

True about myosin?

a) Thin filament

b) Covers active site of action

c) Has ATPase activity

d) Ca+ binding protein

Explanation: Myosin is the major contractile protein comprising the Thick Filament (Actin forms the Thin filament). It does not cover the active site; that is the function of Tropomyosin in the resting state. It does not bind Calcium directly to initiate contraction; Calcium binds to Troponin C on the thin filament. The defining functional characteristic of the Myosin head is that it acts as an enzyme: it possesses ATPase activity. It hydrolyzes ATP to ADP and Pi, storing the energy required for the power stroke and muscle contraction. Therefore, the correct answer is c) Has ATPase activity.

1. The detachment of the myosin cross-bridge from the actin filament is strictly dependent on the binding of:

a) Calcium ions

b) ADP

c) ATP

d) Magnesium

Explanation: The cross-bridge cycle involves distinct steps governed by ATP processing. The hydrolysis of ATP "cocks" the myosin head. The release of Inorganic Phosphate (Pi) triggers the Power Stroke. The release of ADP leaves the myosin head attached to actin in a low-energy "rigor" state. For the myosin head to detach and begin a new cycle, a new molecule of ATP must bind to the nucleotide-binding pocket on the myosin head. In the absence of ATP (as in death), detachment cannot occur, leading to Rigor Mortis. Therefore, the correct answer is c) ATP.

2. Which structural component of the sarcomere remains constant in length during skeletal muscle contraction?

a) I Band

b) H Zone

c) A Band

d) Distance between Z lines

Explanation: According to the Sliding Filament Theory, contraction involves the interdigitation of filaments, not the shortening of the filaments themselves. The A Band corresponds to the entire length of the Thick filaments (Myosin). Since the myosin filaments do not shorten, the width of the A Band remains constant. The I Band (thin filaments only) and the H Zone (thick filaments only) both shorten as the overlap increases. The distance between Z lines (the sarcomere length) decreases. Therefore, the correct answer is c) A Band.

3. A 10-year-old boy presents with progressive muscle weakness and calf pseudohypertrophy. He is diagnosed with Duchenne Muscular Dystrophy. This condition is caused by a defect in Dystrophin, a protein that links actin to:

a) The Z-disk

b) The M-line

c) The Transverse Tubules

d) The Sarcolemma and Extracellular Matrix

Explanation: Dystrophin is a massive cytoskeletal protein located on the inner surface of the muscle cell membrane (sarcolemma). Its crucial function is to mechanically link the internal cytoskeleton (specifically the Actin filaments) to the transmembrane Dystrophin-Glycoprotein Complex (DGC), which anchors the fiber to the Extracellular Matrix (laminin). This linkage stabilizes the sarcolemma during contraction. Absence of dystrophin leads to membrane fragility, calcium influx, and necrosis of muscle fibers (DMD). It does not link to Z-disks (Titin/Alpha-actinin do that). Therefore, the correct answer is d) The Sarcolemma and Extracellular Matrix.

4. During the resting state of skeletal muscle, the interaction between actin and myosin is physically blocked by:

a) Troponin C

b) Titin

c) Tropomyosin

d) Myosin Light Chains

Explanation: Regulation of contraction occurs on the thin filament. In the absence of Calcium (resting state), the filamentous protein Tropomyosin lies directly over the myosin-binding groove on the actin helix. This creates "steric hindrance," physically blocking the myosin heads from attaching to actin. When Calcium is released, it binds to Troponin C, causing a conformational change in the Troponin complex that pulls Tropomyosin aside, uncovering the active sites and allowing cross-bridge formation. Therefore, the correct answer is c) Tropomyosin.

5. The myosin molecule is a hexamer composed of:

a) 1 Heavy chain and 5 Light chains

b) 2 Heavy chains and 4 Light chains

c) 4 Heavy chains and 2 Light chains

d) 6 Heavy chains

Explanation: The myosin II molecule (skeletal muscle myosin) is a large protein complex. It is composed of Two Heavy Chains and Four Light Chains (Total = 6 polypeptide chains). The heavy chains coil around each other to form the "tail" and diverge to form the two globular "heads." Each head is associated with two light chains: one Essential Light Chain (stabilizes the head) and one Regulatory Light Chain (regulates ATPase activity, especially in smooth muscle). Therefore, the correct answer is b) 2 Heavy chains and 4 Light chains.

6. In the length-tension relationship of skeletal muscle, the active tension is maximal when:

a) The muscle is fully stretched (no overlap)

b) The muscle is fully shortened (actin overlap)

c) There is optimal overlap between thick and thin filaments

d) The passive tension is zero

Explanation: The force generated by a muscle fiber is directly proportional to the number of cross-bridges formed between actin and myosin. This depends on the sarcomere length. At Optimal Length (L0) (usually 2.0 - 2.2 micrometers), there is maximal overlap between the myosin heads and actin filaments, allowing the maximum number of cross-bridges to form. If the muscle is stretched too far (no overlap) or shortened too much (actin filaments overlap each other and hit Z-disks), the number of effective cross-bridges decreases, reducing active tension. Therefore, the correct answer is c) There is optimal overlap between thick and thin filaments.

7. Which protein acts as a "molecular ruler" determining the precise length of the actin (thin) filaments during muscle development?

a) Titin

b) Nebulin

c) Desmin

d) Alpha-actinin

Explanation: The sarcomere contains giant accessory proteins that maintain structural integrity. Nebulin is a large, non-elastic protein that runs along the entire length of the thin filament. It is thought to act as a "Molecular Ruler," dictating the precise length of the actin polymer during assembly. In contrast, Titin is the molecular ruler and spring for the thick filament and provides resting elasticity. Alpha-actinin anchors actin to the Z-disk. Desmin connects Z-disks of adjacent myofibrils. Therefore, the correct answer is b) Nebulin.

8. The "S1 fragment" obtained by proteolytic cleavage of myosin contains which functional domains?

a) Tail region for filament assembly

b) Binding sites for Actin and ATP

c) Binding sites for Troponin and Tropomyosin

d) Hinge region only

Explanation: Proteolytic digestion of myosin (using papain or trypsin) yields specific fragments: Light Meromyosin (LMM) and Heavy Meromyosin (HMM). HMM is further split into S1 and S2. The S1 fragment corresponds to the globular Myosin Head. This is the functional "business end" of the molecule. It contains the Binding site for Actin and the ATPase enzymatic pocket (binding site for ATP). The tail (LMM) is for self-assembly into filaments. The S2 is the flexible neck. Therefore, the correct answer is b) Binding sites for Actin and ATP.

9. Which subunit of the Troponin complex mediates the inhibition of the actin-myosin interaction in the absence of calcium?

a) Troponin C

b) Troponin T

c) Troponin I

d) Calmodulin

Explanation: The Troponin complex has three distinct subunits with specific functions. Troponin T (TnT) binds the complex to Tropomyosin. Troponin C (TnC) is the calcium-binding sensor. Troponin I (TnI) is the Inhibitory subunit. In the resting state, TnI binds strongly to actin, holding the tropomyosin in the blocking position and inhibiting ATPase activity. Upon calcium binding to TnC, the interaction between TnI and actin is weakened, allowing tropomyosin to move. TnI levels in blood are markers for cardiac muscle damage. Therefore, the correct answer is c) Troponin I.

10. Smooth muscle myosin differs from skeletal muscle myosin in that its interaction with actin is primarily regulated by:

a) Troponin C binding to Calcium

b) Phosphorylation of the Regulatory Light Chain

c) Direct binding of Calcium to the Heavy chain

d) Removal of Tropomyosin

Explanation: This is a fundamental difference between muscle types. Skeletal muscle is "thin-filament regulated" (Calcium binds Troponin C). Smooth muscle lacks Troponin. Instead, it is "thick-filament regulated." Calcium binds to Calmodulin, and the Ca-Calmodulin complex activates an enzyme called Myosin Light Chain Kinase (MLCK). MLCK then Phosphorylates the Regulatory Light Chain on the myosin head. Only the phosphorylated form of smooth muscle myosin can interact with actin to cause contraction. Therefore, the correct answer is b) Phosphorylation of the Regulatory Light Chain.

Chapter: General Physiology; Topic: Nerve-Muscle Physiology; Subtopic: Ultrastructure of Cardiac vs. Skeletal Muscle

Key Definitions & Concepts

• T-Tubules (Transverse Tubules): Invaginations of the sarcolemma (cell membrane) that penetrate deep into the muscle fiber, allowing the action potential to reach the interior quickly.

• Z Line (Disk): The boundary of the sarcomere; in cardiac muscle, T-tubules are located here.

• A-I Junction: The region where the A band (thick filaments) and I band (thin filaments) overlap; in skeletal muscle, T-tubules are located here.

• Diad (Dyad): The structure formed in cardiac muscle by one T-tubule and one terminal cisterna of the Sarcoplasmic Reticulum (SR).

• Triad: The structure formed in skeletal muscle by one T-tubule and two terminal cisternae of the SR.

• Calcium-Induced Calcium Release (CICR): The mechanism in cardiac muscle where the influx of extracellular Ca2+ through L-type channels triggers the release of stored Ca2+ from the SR.

• L-Type Calcium Channel (DHP Receptor): Voltage-gated channels in the T-tubule; in cardiac muscle, they act as functional Ca2+ channels essential for contraction.

• Ryanodine Receptor (RyR): The Calcium release channel on the SR; RyR2 is the cardiac isoform, while RyR1 is skeletal.

• Intercalated Discs: Specialized cell junctions connecting cardiac myocytes, containing desmosomes (mechanical strength) and gap junctions (electrical continuity).

• Phospholamban: A regulatory protein in cardiac muscle SR that, when phosphorylated (by sympathetic stimulation), increases SERCA activity and relaxation rate.

Lead Question - 2016

In cardiac muscles, T-tubules are present at?

a) Z lines

b) A lines

c) I lines

d) A-I junction

Explanation: There is a distinct anatomical difference between skeletal and cardiac muscle regarding the location of the Transverse Tubules (T-tubules). In mammalian Skeletal Muscle, the T-tubules are located at the A-I Junctions (the overlap between actin and myosin). Since there are two A-I junctions per sarcomere, skeletal muscle has two T-tubules per sarcomere. In contrast, in Cardiac Muscle (ventricular myocytes), the T-tubules are located at the Z lines (Z disks). Because there is only one Z line per sarcomere end (sharing with the next), there is effectively one T-tubule per sarcomere. Cardiac T-tubules are also significantly wider (larger diameter) than skeletal ones. Therefore, the correct answer is a) Z lines.

1. Which of the following structural arrangements represents the Calcium release unit in mammalian Cardiac muscle?

a) Triad located at the Z line

b) Triad located at the A-I junction

c) Diad located at the Z line

d) Diad located at the A-I junction

Explanation: The interaction between the T-tubule and the Sarcoplasmic Reticulum (SR) differs between muscle types. In skeletal muscle, one T-tubule is flanked by two terminal cisternae of the SR, forming a "Triad." In Cardiac muscle, the SR is less well-developed and does not form extensive terminal cisternae. Instead, small expansions of the SR make contact with the T-tubule. Usually, a single T-tubule associates with a single subsarcolemmal SR cisterna, forming a Diad (or Dyad). As established in the lead question, these cardiac T-tubules (and thus the Diads) are located at the Z line. Therefore, the correct answer is c) Diad located at the Z line.

2. The mechanism of Excitation-Contraction coupling in cardiac muscle differs from skeletal muscle because cardiac muscle is dependent on:

a) Mechanical coupling between DHP and RyR

b) Influx of extracellular Calcium (Calcium-Induced Calcium Release)

c) Sodium influx only

d) Complete independence from extracellular ions

Explanation: In skeletal muscle, the DHP receptor acts as a mechanical voltage sensor that physically pulls open the Ryanodine receptor (RyR1). Extracellular Ca2+ is not required for the release signal. In Cardiac muscle, the DHP receptor acts as a true Calcium channel. Depolarization opens these L-type channels, allowing a small amount of Extracellular Calcium to enter the cell. This entering Calcium ("trigger calcium") binds to the Ryanodine Receptors (RyR2) on the SR, causing them to open and release a massive amount of stored Calcium. This process is called Calcium-Induced Calcium Release (CICR). Therefore, the correct answer is b) Influx of extracellular Calcium (Calcium-Induced Calcium Release).

3. A patient with heart failure is prescribed a drug that inhibits the Na+/K+ ATPase. This leads to increased contractility. This mechanism works because the resulting intracellular Sodium accumulation directly affects the function of which transporter near the T-tubule?

a) SERCA pump

b) Na+/Ca2+ Exchanger (NCX)

c) L-type Calcium Channel

d) Ryanodine Receptor

Explanation: This describes the mechanism of Digoxin (Cardiac Glycosides). The Na+/K+ ATPase normally keeps intracellular Na+ low. Inhibition leads to increased intracellular Na+. This reduces the gradient for the Na+/Ca2+ Exchanger (NCX), which is located on the sarcolemma and T-tubules. The NCX normally pumps Ca2+ out using the energy of Na+ coming in. If intracellular Na+ is high, the gradient is weaker, and the NCX works less effectively (or reverses). Consequently, less Calcium is extruded, leading to higher intracellular Calcium, increased SR loading, and stronger contractions (positive inotropy). Therefore, the correct answer is b) Na+/Ca2+ Exchanger (NCX).

4. Structurally, how do the T-tubules of cardiac muscle compare to those of skeletal muscle?

a) Cardiac T-tubules are narrower and more numerous

b) Cardiac T-tubules are wider and fewer in number

c) Cardiac T-tubules are absent

d) Cardiac T-tubules are arranged longitudinally

Explanation: Anatomical adaptations reflect function. Cardiac T-tubules are significantly Wider (larger diameter, about 5 times wider) than those in skeletal muscle. This allows for easier diffusion of ions and nutrients into the deep myofibrils and provides a reservoir of extracellular calcium (glycocalyx helps trap Ca2+ here). However, because they are located only at the Z lines (1 per sarcomere) rather than the A-I junctions (2 per sarcomere), there are Fewer T-tubules in cardiac muscle compared to skeletal muscle. Therefore, the correct answer is b) Cardiac T-tubules are wider and fewer in number.

5. The Ryanodine Receptor isoform found in the Sarcoplasmic Reticulum of cardiac muscle is:

a) RyR1

b) RyR2

c) RyR3

d) IP3 Receptor

Explanation: The Calcium release channels on the Sarcoplasmic Reticulum are known as Ryanodine Receptors (RyR). There are distinct isoforms. RyR1 is the skeletal muscle isoform, which is physically coupled to the DHP receptor. RyR2 is the Cardiac muscle (and brain) isoform, which is activated by Calcium binding (CICR). RyR3 is found in the brain and other tissues. Mutations in RyR1 are associated with Malignant Hyperthermia, while mutations in RyR2 are associated with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Therefore, the correct answer is b) RyR2.

6. A calcium channel blocker like Verapamil exerts its negative inotropic effect by acting on which protein located in the T-tubule membrane?

a) Ryanodine Receptor

b) Na+/Ca2+ Exchanger

c) L-type Calcium Channel (DHP receptor)

d) T-type Calcium Channel

Explanation: Verapamil and Diltiazem are non-dihydropyridine calcium channel blockers. They target the L-type Voltage-Gated Calcium Channels located on the sarcolemma and within the T-tubules. In cardiac muscle, the influx of calcium through these channels is the absolute requirement to trigger contraction (Trigger Calcium). Blocking these channels reduces the amount of trigger calcium entering during the plateau phase (Phase 2), thereby reducing the amount of calcium released from the SR, leading to decreased force of contraction (Negative Inotropy). Therefore, the correct answer is c) L-type Calcium Channel (DHP receptor).

7. Phospholamban is a regulatory protein found in the SR membrane of cardiac muscle. When phosphorylated by Protein Kinase A (during sympathetic stimulation), it:

a) Inhibits the L-type Calcium channel

b) Inhibits SERCA, slowing relaxation

c) Relieves inhibition of SERCA, accelerating relaxation

d) Closes the Ryanodine Receptor

Explanation: In the resting state, unphosphorylated Phospholamban acts as a "brake" or inhibitor of the SERCA pump (Sarcoplasmic Endoplasmic Reticulum Calcium ATPase). During sympathetic stimulation (fight or flight), Beta-adrenergic stimulation leads to PKA activation. PKA phosphorylates Phospholamban. This phosphorylation removes the inhibition on SERCA. Consequently, SERCA pumps Calcium back into the SR faster and more efficiently. This accelerates muscle relaxation (Positive Lusitropy) and increases the SR calcium stores for the next beat (contributing to Positive Inotropy). Therefore, the correct answer is c) Relieves inhibition of SERCA, accelerating relaxation.

8. In skeletal muscle, the T-tubules are located at the A-I junction. This means there are how many T-tubules per sarcomere?

a) One

b) Two

c) Three

d) Four

Explanation: A sarcomere extends from one Z line to the next Z line. It contains one full A band in the center and two half I bands on either side. The boundary between the A band and the I band is the A-I Junction. Since there is an A-I junction on both sides of the A band within a single sarcomere, there are Two A-I junctions. Consequently, in skeletal muscle where T-tubules are located at these junctions, there are Two T-tubules per sarcomere. This contrasts with the single T-tubule (at the Z line) in cardiac muscle. Therefore, the correct answer is b) Two.

9. The electrical continuity between adjacent cardiac muscle cells, allowing them to function as a syncytium, is provided by:

a) T-tubules

b) Desmosomes

c) Gap Junctions

d) Fascia adherens

Explanation: Cardiac muscle cells are connected end-to-end by specialized structures called Intercalated Discs. These discs contain three types of junctions. Fascia adherens and Desmosomes provide mechanical strength, holding the cells together during contraction. Gap Junctions (Connexons) provide low-resistance electrical pathways that allow ions to flow freely from one cell to the next. This ensures that the action potential spreads rapidly across the entire heart muscle, allowing the ventricles to contract as a single coordinated unit or functional syncytium. Therefore, the correct answer is c) Gap Junctions.

10. Unlike skeletal muscle, cardiac muscle contraction cannot be tetanized (sustained contraction without relaxation). This is primarily due to:

a) The absence of Troponin

b) The very short refractory period

c) The long Absolute Refractory Period overlapping with contraction

d) The lack of T-tubules

Explanation: Tetanization requires high-frequency stimulation where new action potentials are generated before the muscle has relaxed from the previous twitch. In cardiac muscle, the Action Potential is very long (due to the L-type Ca2+ plateau). Consequently, the Absolute Refractory Period (time when Na+ channels are inactivated) is also extremely long (almost as long as the mechanical contraction itself). By the time the membrane is excitable again, the muscle has already begun to relax. This protective mechanism prevents summation and tetanus, which would be fatal for the heart's pumping function (filling requires relaxation). Therefore, the correct answer is c) The long Absolute Refractory Period overlapping with contraction.

Chapter: General Physiology; Topic: Nerve-Muscle Physiology; Subtopic: Structure of the Sarcomere

Key Definitions & Concepts

• Sarcomere: The functional contractile unit of a muscle fiber; defined as the segment between two consecutive Z lines (disks).

• A Band (Anisotropic): The dark band containing the entire length of the Thick filaments (Myosin) and the overlapping parts of the Thin filaments. Its length remains constant during contraction.

• I Band (Isotropic): The light band containing only Thin filaments (Actin) and no thick filaments. It spans across two adjacent sarcomeres, bisected by the Z line.

• H Zone: The central region of the A Band containing only thick filaments (no actin overlap). It shortens/disappears during contraction.

• Z Line: The dark line bisecting the I Band; anchors the thin filaments.

• M Line: The dark line in the center of the H zone; anchors the thick filaments.

• Sarcomere Length Formula: Length = Length of A Band + (2 x Half-I Band). Since the "I Band" usually refers to the *full* light band spanning two sarcomeres, the portion *within* one sarcomere is two halves, equaling the total width of one I band. Thus, Sarcomere = A Band + I Band (width).

• Sliding Filament Theory: During contraction, thin filaments slide over thick filaments. The Z lines move closer together, shortening the I band and H zone, but the A band length is unchanged.

• Optimal Length: The sarcomere length (2.0-2.2 µm) at which maximal tension can be generated due to optimal overlap.

• Titin: A giant elastic protein connecting the Z line to the M line, stabilizing the thick filament.

Lead Question - 2016

In a muscle fiber at rest, the length of the I band is 1 mm and A band is 1.5 mm. What is the length of the sarcomere?

a) 0.5 mm

b) 2.5 mm

c) 3.5 mm

d) 5 mm

Explanation: A single sarcomere extends from one Z-line to the next Z-line. The structure consists of one full A Band in the center. Flanking the A band on either side is half of an I Band (since the full I band is bisected by the Z-line and shared between two sarcomeres). Therefore, the total length of one sarcomere = Length of A Band + (Length of ½ I Band + Length of ½ I Band). Mathematically, this simplifies to: Sarcomere Length = Length of A Band + Length of one full I Band. Given: A Band = 1.5 mm (micrometers usually, but mm in question), I Band = 1.0 mm. Calculation: 1.5 + 1.0 = 2.5 mm. Therefore, the correct answer is b) 2.5 mm.

1. Which band of the sarcomere disappears completely during maximal skeletal muscle contraction?

a) A Band

b) Z Line

c) H Zone

d) M Line

Explanation: During contraction, the thin filaments (actin) slide over the thick filaments (myosin) toward the center of the sarcomere (M line). The H Zone is the central part of the A band that, in a resting state, contains only myosin and no actin overlap. As the actin filaments slide inward, they invade the H zone. At maximal contraction, the actin filaments from opposite sides meet (and may even overlap) at the center, causing the H Zone to disappear completely. The I band also narrows significantly but doesn't technically disappear until extreme shortening. The A band remains constant. Therefore, the correct answer is c) H Zone.

2. The "Z-line" (Zwischenscheibe) creates the physical boundary of the sarcomere. Which protein is the primary structural component anchoring Actin filaments to the Z-line?

a) Myomesin

b) Alpha-actinin

c) Titin

d) Desmin

Explanation: The Z-line is a dense protein disc. The thin filaments (Actin) are anchored here. The primary protein responsible for cross-linking the actin filaments to the Z-disc lattice is Alpha-actinin. Myomesin is found at the M-line (anchoring myosin). Titin connects the Z-line to the M-line (providing elasticity). Desmin forms intermediate filaments that connect adjacent Z-lines (sarcomeres) to each other laterally, keeping myofibrils aligned. Therefore, the correct answer is b) Alpha-actinin.

3. Which protein extends from the Z-line to the M-line and is responsible for the passive elasticity (resting tension) of the muscle?

a) Nebulin

b) Dystrophin

c) Titin

d) Tropomyosin

Explanation: Titin (Connectin) is a giant protein (the largest known). It spans half the sarcomere, anchoring the thick filament to the Z-line and extending to the M-line. A portion of the Titin molecule in the I-band region acts like a molecular spring. When the muscle is stretched, Titin uncoils, generating Passive Tension (elastic recoil) that prevents overstretching and helps the muscle return to its resting length. Nebulin acts as a ruler for actin length. Dystrophin connects the cytoskeleton to the membrane. Therefore, the correct answer is c) Titin.

4. The "M Line" (Mittelscheibe) is located in the center of the sarcomere. It serves as the attachment point for:

a) Thin filaments

b) Thick filaments

c) Z-discs

d) T-tubules

Explanation: The sarcomere has structural symmetry. While the Z-line anchors the thin filaments at the ends, the M Line acts as the anchor point for the Thick filaments (Myosin) in the center of the sarcomere. Proteins like Myomesin and C-protein are found here, holding the myosin bundles in a hexagonal lattice. This anchoring ensures that the thick filaments remain centered during the sliding process of contraction. The enzyme Creatine Kinase is also located at the M-line to regenerate ATP. Therefore, the correct answer is b) Thick filaments.

5. Which band of the sarcomere contains the enzyme Creatine Kinase to rapidly regenerate ATP?

a) Z Line

b) I Band

c) M Line

d) Actin-Myosin Overlap zone

Explanation: Muscle contraction requires immediate ATP availability. The enzyme Creatine Kinase (MM isoform) transfers a phosphate group from Phosphocreatine to ADP to regenerate ATP. Structurally, this enzyme is bound to the M Line (within the A band) of the sarcomere. This strategic location places the ATP-regenerating machinery right next to the Myosin heads (which are the ATPases) in the center of the thick filament array, ensuring efficient energy supply during contraction. Therefore, the correct answer is c) M Line.

6. In the cross-section of a myofibril at the A-I overlap zone, each Thick filament is surrounded by how many Thin filaments?

a) 2

b) 3

c) 4

d) 6

Explanation: The myofilaments are arranged in a precise hexagonal lattice. In the region where actin and myosin overlap (A band), each Thick filament (Myosin) is surrounded by a hexagonal array of 6 Thin filaments (Actin). Conversely, each Thin filament sits in the center of a triangle formed by 3 Thick filaments. This 1:6 (or 2:1 ratio overall) geometry allows each myosin head to interact with multiple actin filaments, maximizing force generation. Therefore, the correct answer is d) 6.

7. If the length of a sarcomere is stretched beyond 3.65 micrometers, the active tension developed drops to zero because:

a) Titin breaks

b) There is no overlap between thick and thin filaments

c) The H zone disappears

d) Calcium cannot bind to Troponin

Explanation: The Length-Tension relationship is fundamental to muscle physiology. Active tension depends on the number of cross-bridges formed. At a sarcomere length of ~3.65 µm (in frog muscle, often cited as the limit), the actin filaments are pulled completely out of the A band. Consequently, There is no overlap between thick and thin filaments. Without overlap, myosin heads cannot bind to actin, no cross-bridges can form, and the active tension generated is zero. The muscle is "disengaged." Therefore, the correct answer is b) There is no overlap between thick and thin filaments.

8. Which of the following proteins serves as a "molecular ruler" to regulate the length of the Thin (Actin) filament?

a) Titin

b) Nebulin

c) Myomesin

d) Obscurin

Explanation: The precise length of filaments is critical for the crystalline structure of the sarcomere. Nebulin is a large, non-elastic filamentous protein that runs along the entire length of the Thin Filament (Actin). It is anchored at the Z-line. It is thought to act as a "Molecular Ruler" that dictates exactly how long the actin polymer grows during muscle development. Titin performs a similar ruler/scaffold function for the Thick filament (Myosin). Therefore, the correct answer is b) Nebulin.

9. During isotonic contraction, which measurement changes?

a) Length of the A band

b) Length of the Myosin filament

c) Length of the I band

d) Length of the Actin filament

Explanation: In isotonic contraction, the muscle shortens. Based on the sliding filament theory: 1. Actin and Myosin filament lengths remain constant. 2. The A band (Myosin length) remains constant. 3. The filaments slide past each other. 4. The Z-lines move closer together. 5. This shortening of the sarcomere occurs at the expense of the I Band and the H Zone, which both decrease in length (shorten). Therefore, the visible change is in the I band. Therefore, the correct answer is c) Length of the I band.

10. The region of the sarcomere containing ONLY Actin filaments is the:

a) A Band

b) H Zone

c) I Band

d) M Line

Explanation: Definitions are key here. A Band = Length of Myosin (includes Actin overlap). H Zone = Center of A Band with Myosin ONLY. I Band = The light band spanning the Z-line, containing ONLY Actin (Thin) filaments (no Myosin). M Line = Center anchor for Myosin. Therefore, the region exclusively containing actin is the I Band. Therefore, the correct answer is c) I Band.