Week 11
Explain how clinicians distinguish between nociceptive, neuropathic, inflammatory, and psychogenic pain. Give examples
Nociceptive pain:
Cause: Tissue injury (muscle, bone, skin).
Clues: Sharp, aching, throbbing; pain matches injury site.
Example: Sprained ankle, fracture.
Neuropathic pain:
Cause: Nerve damage or dysfunction.
Clues: Burning, shooting, tingling, “electric.”
Example: Diabetic neuropathy, sciatica.
Inflammatory pain:
Cause: Immune activation and tissue inflammation.
Clues: Redness, warmth, swelling, tenderness.
Example: Rheumatoid arthritis, gout.
Psychogenic pain:
Cause: Psychological factors strongly influencing pain perception.
Clues: Pain worsens with stress, anxiety, trauma; exam may not match severity.
Example: Tension headaches, somatic symptom disorder.
Describe the steps of olfactory transduction starting from odorant binding to the generation of an action potential in the olfactory sensory neuron.
Odorant binds to an olfactory GPCR on the cilia of the olfactory sensory neuron.
The GPCR activates, α-subunit leaves and activates adenylate cyclase.
Adenylate cyclase converts ATP → cAMP.
cAMP channels open, Na+ and Ca2+ enter
If the depolarization reaches threshold, an action potential is generated in the olfactory sensory neuron and carried along the olfactory nerve to the brain.
Describe the steps of a somatic reflex and explain how they differ from the steps of an autonomic reflex.
A somatic reflex is a rapid, involuntary response that involves skeletal muscles. The steps typically are:
Stimulus detection – A sensory receptor detects a change (e.g., touching a hot object).
Afferent signal – Sensory neurons transmit the signal to the spinal cord.
Integration – Interneurons in the spinal cord process the signal.
Efferent signal – Motor neurons carry the response signal back to skeletal muscles.
Effector response – The skeletal muscle contracts, producing a reflex action.
Autonomic reflexes, in contrast, control smooth muscle, cardiac muscle, or glands and have some differences:
They usually involve two neurons in the efferent pathway (preganglionic and postganglionic neurons) instead of just one motor neuron.
The integration can occur in the spinal cord or brainstem, depending on the reflex.
The effectors are involuntary tissues (heart, glands, smooth muscle), producing responses like changes in heart rate, digestion, or pupil size.
So, the main differences are effector type (skeletal vs. smooth/cardiac/gland) and neuron arrangement (single motor neuron vs. two-neuron chain).
Macular degeneration primarily affects the region containing the fovea. Explain why this results in significant functional vision loss.
The fovea is the central part of the macula responsible for high-acuity vision because it has a high density of cone photoreceptors and a direct, one-to-one connection to bipolar and ganglion cells.
In macular degeneration, the fovea and surrounding macula are damaged, which leads to:
Loss of central vision, making tasks like reading, recognizing faces, and fine detail work very difficult.
Relatively preserved peripheral vision, because rods in the peripheral retina are less affected, so patients may still see around the edges but not centrally.
Compare A-delta and C fibers in terms of conduction velocity, myelination, and the type of pain they mediate. Why do we experience sharp pain followed by dull pain?
Conduction velocity:
A-delta: fast (5–30 m/s) → rapid pain transmission
C fibers: slow (0.5–2 m/s) → delayed pain transmission
Myelination:
A-delta: thinly myelinated
C fibers: unmyelinated
Type of pain:
A-delta: sharp, well-localized, “first” pain
C fibers: dull, burning, aching, poorly localized, “second” pain
Explain how TRP channels contribute to pain sensation. Include at least two stimuli that activate different TRP channel types.
TRP channels are ion channels on sensory neurons that open in response to specific stimuli, allowing ions in and triggering pain signals to the brain. Some sense heat, cold, pain etc.
Describe how hair cells in the Organ of Corti convert mechanical vibrations into neural signals. Include what happens when stereocilia bend toward vs. away from the kinocilium.
1. Sound vibrations → basilar membrane movement
Sound waves vibrate the basilar membrane in the cochlea.
Hair cells in the Organ of Corti move up and down with the membrane.
2. Stereocilia bend due to shearing force
The tectorial membrane stays relatively still, so the movement creates a shear that bends the stereocilia on top of each hair cell.
3. Bending toward the kinocilium = depolarization
Tip links stretch and open mechanically gated K⁺ channels.
Endolymph (which is K⁺-rich) drives K⁺ into the hair cell.
Cell depolarizes, opens Ca²⁺ channels, and increases neurotransmitter release onto the auditory nerve.
4. Bending away from the kinocilium = hyperpolarization
Tip links relax → K⁺ channels close.
Less K⁺ enters → the hair cell hyperpolarizes.
Neurotransmitter release decreases.
5. Result:
The auditory nerve converts this pattern of depolarization/hyperpolarization into neural signals that encode sound frequency and intensity.
Discuss how the location and length of pre-ganglionic and post-ganglionic neurons in each branch of the ANS influence their function.
Sympathetic division (fight or flight):
Pre-ganglionic neurons are short and located in the thoracolumbar spinal cord (T1–L2).
Post-ganglionic neurons are long, extending from sympathetic ganglia near the spinal cord to distant target organs.
This arrangement allows rapid, widespread activation because one pre-ganglionic neuron can synapse with many post-ganglionic neurons.
Parasympathetic division (rest and digest):
Pre-ganglionic neurons are long and located in the brainstem or sacral spinal cord.
Post-ganglionic neurons are short, close to or within target organs.
This setup enables localized, precise control of organ function rather than a mass response.
In short: short pre + long post = broad, fast response (sympathetic); long pre + short post = targeted, fine-tuned response (parasympathetic).
Explain how the RPE (retinal pigment epithelium) supports photoreceptors and how dysfunction of the RPE contributes to AMD.
Nutrient and waste management: It transports nutrients from the choroid to photoreceptors and removes metabolic waste.
Photoreceptor renewal: It phagocytoses shed photoreceptor outer segments, preventing toxic buildup.
Light absorption: It absorbs stray light to improve visual contrast and reduce phototoxic damage.
Visual cycle support: It regenerates 11-cis-retinal, the chromophore needed for phototransduction.
RPE dysfunction, as seen in age-related macular degeneration (AMD), disrupts these processes:
Accumulation of waste products (like drusen) damages photoreceptors.
Impaired nutrient supply and photoreceptor renewal accelerates degeneration.
This leads to central vision loss, especially affecting the fovea where photoreceptor density is highest.
Compare the roles of α-cells and β-cells in the regulation of blood glucose. Include how amylin and glucagon support insulin function or counteract it.
β-cells:
Secrete insulin, which lowers blood glucose by promoting uptake into muscle and fat, and stimulating glycogen and fat storage.
Also secrete amylin, which slows gastric emptying and suppresses post-meal glucagon, supporting insulin’s glucose-lowering effect.
α-cells:
Secrete glucagon, which raises blood glucose by stimulating glycogen breakdown and gluconeogenesis in the liver.
During fasting or low glucose, glucagon counteracts insulin to maintain adequate blood glucose.
Trace the pain sensory pathway from a painful stimulus in the periphery all the way to the somatosensory cortex. Identify the three neuron types and what happens at each synapse.
1. First-order neuron (peripheral → spinal cord):
Nociceptors in the skin detect the painful stimulus.
The first-order neuron carries the signal through the dorsal root and synapses in the dorsal horn of the spinal cord.
Neurotransmitters: glutamate and substance P.
2. Second-order neuron (spinal cord → thalamus):
The second-order neuron crosses (decussates) to the opposite side in the spinal cord.
Ascends in the spinothalamic tract.
Synapses in the thalamus (ventral posterior nucleus).
3. Third-order neuron (thalamus → cortex):
The third-order neuron projects from the thalamus to the primary somatosensory cortex.
This is where the brain localizes and interprets the pain.
Compare how the semicircular canals and the utricle/saccule detect different kinds of movement.
Semicircular Canals (Rotational / Angular Movement):
Detect head rotation (shaking yes/no, turning your head).
Filled with endolymph; movement of the fluid bends hair cells in the ampulla.
Respond best to changes in rotation (start/stop turning).
Utricle and Saccule (Linear Movement & Gravity):
Detect linear acceleration (moving forward, up/down) and head tilt relative to gravity.
Hair cells sit under a gel layer with otoliths (tiny calcium crystals) that shift with movement or tilt.
Respond to constant position (like leaning your head sideways) and straight-line motion.
Describe the major differences between lipophilic and hydrophilic hormones
Solubility:
Lipophilic (e.g., steroid hormones, thyroid hormones) dissolve in lipids/fats.
Hydrophilic (e.g., peptide and catecholamine hormones) dissolve in water.
Transport in blood:
Lipophilic hormones need carrier proteins to travel in blood.
Hydrophilic hormones are freely soluble in plasma.
Receptor location:
Lipophilic hormones bind to intracellular receptors (cytoplasm or nucleus).
Hydrophilic hormones bind to membrane receptors on the cell surface.
Mechanism of action:
Lipophilic hormones often regulate gene transcription and have slower, long-lasting effects.
Hydrophilic hormones usually trigger second messenger cascades, producing fast, short-term effects.
Explain the roles of insulin and glucagon in maintaining normal blood glucose levels. How do they balance each other during fasting versus after a meal?
Insulin and glucagon are key pancreatic hormones that maintain blood glucose within a narrow range:
Insulin (from β-cells) lowers blood glucose by promoting glucose uptake into muscle and fat, and stimulating glycogen and fat synthesis.
Glucagon (from α-cells) raises blood glucose by stimulating glycogen breakdown and gluconeogenesis in the liver.
During a meal:
Blood glucose rises → insulin dominates → glucose is stored in tissues and blood levels normalize.
During fasting:
Blood glucose drops → glucagon dominates → liver releases glucose to maintain energy supply, especially for the brain.
The sympathetic and parasympathetic systems often have opposite effects. Choose three organs and explain how each system affects that organ
Heart:
SNS: Increases heart rate and contractility to boost blood flow during stress (“fight or flight”).
PNS: Decreases heart rate via the vagus nerve, promoting rest and energy conservation.
Pupil of the eye:
SNS: Dilates pupils to improve vision in low light or during alertness.
PNS: Constricts pupils for near vision and protection from bright light.
Digestive tract:
SNS: Reduces peristalsis and secretion, slowing digestion to redirect energy elsewhere.
PNS: Stimulates peristalsis and enzyme secretion, promoting nutrient absorption and “rest and digest.”
Outline the steps of GPCR activation starting from ligand binding.
ligand binds to the GPCR
GPCR changes shape and activates the G-protein
The G-protein’s α subunit exchanges GDP for GTP.
α subunit leaves and activates something else
The α subunit hydrolyzes GTP → GDP, turning itself off.
α recombines with βγ (beta and gamma), returning the G-protein to its resting state.
Describe the molecular steps of the phototransduction cascade
Photon hits rhodopsin, changing the shape of retinal molecule
Activated rhodopsin activates the G-protein
α-subunit activates PDE (phosphodiesterase).
PDE breaks down cGMP → GMP, lowering cGMP levels.
Low cGMP causes cGMP-gated Na⁺/Ca²⁺ channels to close.
With channels closed, the photoreceptor hyperpolarizes.
Hyperpolarization reduces glutamate release at the synapse with bipolar cells.
Bipolar and ganglion cells adjust their activity → neural signal sent to the brain.
explain how negative feedback operates in both the HPT and HPA axes
HPT axis:
The hypothalamus releases TRH (thyrotropin-releasing hormone).
TRH stimulates the anterior pituitary to release TSH (thyroid-stimulating hormone).
TSH stimulates the thyroid gland to release T3 and T4.
High levels of T3/T4 inhibit TRH and TSH release, preventing overproduction.
HPA axis:
The hypothalamus releases CRH (corticotropin-releasing hormone).
CRH stimulates the anterior pituitary to release ACTH (adrenocorticotropic hormone).
ACTH stimulates the adrenal cortex to release cortisol.
Elevated cortisol inhibits CRH and ACTH release, preventing excess cortisol.
In both axes, the end hormone signals back to the hypothalamus and pituitary to shut off further stimulation, keeping the system stable.
Explain why a person who is athletic or normal weight can still develop Type II diabetes
Genetics: Some people inherit genes that reduce insulin sensitivity or impair β-cell function.
Age and lifestyle factors: Sedentary habits, poor sleep, or chronic stress can contribute to insulin resistance even in normal-weight people.
Fat distribution: Visceral fat (around organs) is more metabolically active and harmful than subcutaneous fat, so someone can appear lean but still have risky fat deposits.
β-cell dysfunction: Over time, even modest insulin resistance can overwhelm pancreatic β-cells, reducing insulin secretion and raising blood glucose.
Explain how hormone receptors (GPCRs, 1-TMS receptors, and nuclear receptors) differ in mechanism of action
GPCRs (G-protein-coupled receptors):
Located on the cell membrane.
Bind hydrophilic hormones (e.g., epinephrine).
Activate second messenger cascades, producing fast, short-term responses.
1-TMS receptors (single transmembrane-spanning receptors, e.g., receptor tyrosine kinases):
Span the membrane once.
Ligand binding triggers autophosphorylation and downstream signaling pathways , affecting gene expression or metabolism.
Typically mediate slower, longer-lasting responses than GPCRs but faster than nuclear receptors.
Nuclear receptors:
Found in the cytoplasm or nucleus.
Bind lipophilic hormones (steroids, thyroid hormones).
Hormone-receptor complex directly regulates gene transcription, producing slow but long-lasting effects.
Explain the difference between direct and indirect sensory receptor activation. Include TRP channels and GPCRs in your explanation.
Direct activation:
The stimulus directly opens an ion channel, causing ions to flow and creating a receptor potential.
Example: TRP channels (like TRPV1) open directly in response to heat, cold, or chemicals such as capsaicin.
Indirect activation:
The stimulus activates a GPCR, which triggers a second-messenger cascade that eventually opens or closes ion channels.
Example: Olfactory receptors or some nociceptors that use GPCRs to activate downstream signaling before generating a receptor potential.
Explain why photoreceptors have high energy demands and how the retinal pigment epithelium (RPE) protects them from oxidative damage.
Phagocytosing shed photoreceptor outer segments, removing damaged membranes before they build up.
Absorbing excess light with melanin, reducing photo-oxidative stress.
Providing antioxidants and neutralizing ROS.
Maintaining nutrient delivery and waste removal through its tight connection with the choroid.
A patient presents with dilated pupils, elevated heart rate, and reduced salivation. Explain which branch of the ANS is dominant, what neurotransmitters are involved, and why the body would initiate these changes.
Neurotransmitters involved:
Preganglionic neurons release acetylcholine (ACh) onto nicotinic receptors of postganglionic neurons.
Postganglionic neurons release norepinephrine (NE) onto adrenergic receptors in target organs (except for sweat glands, which use ACh).
Why these changes occur:
Dilated pupils improve vision and allow more light in for heightened awareness.
Elevated heart rate increases blood flow to muscles and vital organs.
Reduced salivation conserves energy for essential systems and reduces digestive activity, which isn’t immediately needed for survival.
In a situation where leptin cannot be effectively detected in its target tissues, what would be the effects on blood glucose, insulin, and its target tissues?
higher blood glucose
higher insulin
more hunger and more eating behavior
Explain the difference between direct and indirect sensory receptor activation.
direct = stimulus acts on the receptor itself
indirect = stimulus acts via a chemical signal.