Week 1 Supplement – Comprehensive Study Notes

Sensory Processing – General Senses

• Pathway overview (body excluding face)
  • Peripheral somatic receptor → peripheral nerve → spinal cord (dorsal root & ascending tracts) → thalamus (ventral posterior nuclei) → primary somatosensory cortex (post-central gyrus, parietal lobe) → higher-order association areas.
  • Functional significance
  • Thalamus = master sensory relay; filters/coordinates incoming data before conscious perception.
  • Post-central gyrus maps stimuli via the somatotopic "homunculus," allocating greater cortical area to regions with high receptor density (e.g.
    fingertips, lips).
• Pathway overview (face & anterior scalp)
  • Trigeminal nerve (CN V; ophthalmic, maxillary, mandibular branches) → trigeminal sensory nuclei in brainstem → decussation/ascension → thalamus → primary somatosensory cortex.
  • Clinical note: Lesions in CN V or its nuclei produce ipsilateral facial numbness, contrasting with contralateral body deficits in spinal/medullary lesions.
• General sense modalities covered
  • Touch (fine, crude), pressure, vibration, proprioception, temperature, nociception (pain).
  • Receptor types: mechanoreceptors (Meissner, Pacinian, Merkel, Ruffini), thermoreceptors, nociceptors, proprioceptors (muscle spindles, Golgi tendon organs).

Sensory Processing – Special Senses

• Unified theme: All special-sense pathways (except olfaction) synapse in the thalamus before reaching cortex.
• Taste (Gustation)
  • Cranial nerves: CN VII (facial – anterior 2/3 tongue), CN IX (glossopharyngeal – posterior 1/3), CN X (vagus – epiglottis, pharynx).
  • Pathway: Taste buds → respective cranial nerve → solitary nucleus (medulla) → thalamus (VPM) → gustatory area of post-central gyrus & insula → orbitofrontal integration.
  • Clinical correlation: Ageusia or dysgeusia with CN VII damage; brainstem lesions can selectively abolish contralateral taste.
• Hearing (Audition)
  • Cranial nerve: CN VIII (vestibulocochlear – cochlear division).
  • Pathway: Hair cells in Organ of Corti → spiral ganglion → cochlear nuclei (medulla) → bilateral projections through superior olivary complex & inferior colliculus → thalamus (medial geniculate body) → primary auditory cortex (transverse temporal gyri hidden in lateral sulcus, superior temporal lobe).
  • Key feature: Extensive bilateral crossing ensures partial hearing preservation after unilateral lesions.
• Vision
  • Cranial nerve: CN II (optic nerve) conveying retinal output.
  • Pathway: Retina → optic nerve → optic chiasm (nasal fibers cross) → optic tract → thalamus (lateral geniculate nucleus, LGN) → optic radiations → primary visual cortex (striate cortex, occipital lobe).
  • Additional projections: Superior colliculus (reflexive eye/head movements), pretectal area (pupillary reflex), suprachiasmatic nucleus (circadian rhythm).
• Smell (Olfaction) – unique exception
  • Cranial nerve: CN I (olfactory nerve – technically fila of olfactory receptor neurons).
  • Pathway: Olfactory epithelium → olfactory bulb & tract → primary olfactory cortex (piriform, entorhinal, amygdala) WITHOUT thalamic relay → diverse limbic structures (hippocampus, amygdala), orbitofrontal cortex (conscious odor identification).
  • Notable implications: Rapid memory-emotion link; early degeneration in Alzheimer’s & Parkinson’s.

Vision & Hemispheric Lateralization

• Principle: Each cerebral hemisphere processes the visual field that projects onto the contralateral half of each retina – i.e. left visual field (LVF) → right occipital lobe; right visual field (RVF) → left occipital lobe.
• Motor-sensory coupling
  • The hemisphere that commands right-side motor output also receives LVF input; facilitates eye–hand coordination during tasks (e.g. catching, writing).
• Lesion patterns
  • Optic tract lesion → contralateral homonymous hemianopia (loss of same visual field in both eyes).
  • Occipital stroke respecting calcarine artery sparing macula → macular sparing homonymous hemianopia.

Hypophyseal (Pituitary) Portal System

• Definition: A two-capillary-bed venous network linking hypothalamus to anterior pituitary (adenohypophysis).
• Comparative circulatory patterns
  • Normal systemic: $\text{Heart} \rightarrow \text{Arteries} \rightarrow \text{Arterioles} \rightarrow \text{Capillaries} \rightarrow \text{Venules} \rightarrow \text{Veins} \rightarrow \text{Heart}.$
  • Portal: Same sequence PLUS a second capillary bed before returning to heart: $\text{Heart} \rightarrow \text{Arteries} \rightarrow \text{Arterioles} \rightarrow \text{Capillaries}<em>1 \rightarrow \text{Venules} \rightarrow \text{Capillaries}</em>2 \rightarrow \text{Venules} \rightarrow \text{Veins} \rightarrow \text{Heart}.$
• Functional purpose
  • Delivers releasing/inhibiting hormones (e.g. TRH, CRH, GnRH, GHRH, somatostatin, dopamine) directly and concentrated to anterior pituitary without systemic dilution; permits minute hypothalamic outputs to orchestrate large endocrine responses.
• Clinical relevance
  • Interruption (e.g. pituitary stalk injury) abolishes portal flow → panhypopituitarism; posterior pituitary hormones often spared.

Types of Chemical Secretions

• Exocrine
  • Definition: Secretion to body surface or lumen via ducts.
  • Examples: Sweat, saliva, digestive enzymes (pancreatic juices via pancreatic duct), sebaceous oil.
• Autocrine
  • Definition: Chemical messenger acts on same cell that secreted it; immediate feedback regulation.
  • Example: IL-2 secretion by activated T-cells promotes own proliferation.
• Paracrine
  • Definition: Local diffusion to neighboring cells within same tissue; limited by interstitial distance.
  • Example: Nitric oxide (NO) from endothelium causing vascular smooth-muscle relaxation.
• Endocrine
  • Definition: Classic hormones enter bloodstream, travel long distance to target cells with specific receptors.
  • Example: Insulin from pancreatic β-cells regulating systemic glucose.

Taste Receptors, Opsins & G-Protein-Coupled Receptors (GPCRs)

• Taste chemistry
  • Sweet: Detects sugars; receptor: T1R2/T1R3 GPCR heterodimer.
  • Umami: Detects glutamate/aspartate; receptor: T1R1/T1R3 GPCR.
  • Salty: Detects $\text{Na}^+$ influx through ENaC channels (not GPCR).
  • Sour: Detects $\text{H}^+$ (acid) via PKD2L1 channels/proton-sensitive channels.
  • Bitter: Diverse toxic alkaloids; >25 T2R GPCR subtypes – broad detection spectrum.
• GPCR mechanism (generic)
  • Ligand binds extracellular domain → conformational change → intracellular G-protein (α, β, γ) exchanges $\text{GDP}$ for $\text{GTP}$ on α-subunit → dissociation → α-GTP & βγ activate downstream effectors (adenylyl cyclase, phospholipase C, ion channels) → second-messenger cascades (cAMP, IP3/DAG) → physiological response.
  • Desensitization via phosphorylation (GRKs) & arrestin binding.
• Visual phototransduction
  • Opsins: Light-sensitive GPCR-like proteins; rods express rhodopsin, cones express photopsins (S/M/L – blue/green/red); melanopsin in retinal ganglion cells for circadian regulation.
  • Retinal (vitamin A derivative) covalently bound to opsin; photon converts 11-cis-retinal → all-trans → triggers opsin activation → transducin (G-protein) → cGMP phosphodiesterase → $\downarrow$ cGMP → closure of cGMP-gated $\text{Na}^+/\text{Ca}^{2+}$ channels → hyperpolarization → reduced glutamate release.
  • Wavelength sensitivity determines color perception; genetic defects (e.g. opsin gene mutations) cause color-blindness.

Hormone Chemistry & Transport

• Steroid hormones (derived from cholesterol)
  • Examples: Cortisol, aldosterone, testosterone, estradiol, progesterone, calcitriol.
  • Properties: Hydrophobic/lipophilic, poor aqueous solubility.
  • Plasma transport: Bind carrier proteins (e.g. albumin, CBG, SHBG); creates equilibrium of "bound" vs "free" hormone.
  • Free (unbound) fraction = biologically active; bound fraction = reservoir prolonging half-life.
• Peptide/amine hormones
  • Examples: Insulin, glucagon, growth hormone, catecholamines.
  • Hydrophilic; circulate unbound; act via membrane receptors & second messengers.
• Thyroid hormones (T3, T4)
  • Synthesis requires iodine incorporation into thyroglobulin in thyroid follicular lumen.
  • Lipophilic, but unique amine class; transported bound to TBG, transthyretin, albumin.
• Clinical nugget: Measuring total vs free T4 differentiates binding-protein abnormalities from true thyroid dysfunction.

Bound vs. Free Hormone Concept

• Law of mass action: $\text{H}<em>{\text{free}} + \text{P} \leftrightarrow \text{HP}</em>{\text{bound}}$.
• Only $\text{H}_{\text{free}}$ diffuses into cells, interacts with receptors, and undergoes metabolic clearance.
• Rising binding-protein concentration (e.g. pregnancy ↑ TBG) elevates total hormone but free hormone remains steady after equilibration; hence physiological euthyroid state.

Additional Chemical & Cellular Facts

• Inner-ear hair cells
  • Endolymph (high $\text{K}^+$, low $\text{Na}^+$) bathes stereocilia; mechanical deflection opens tip-link channels → massive $\text{K}^+$ influx (not $\text{Na}^+$), depolarizing cell, triggering $\text{Ca}^{2+}$-mediated neurotransmitter (glutamate) release.
  • Contrast: Most neurons depolarize via $\text{Na}^+$; cochlear design exploits electrochemical gradient between endolymph & perilymph.
• Protein structure basics
  • Primary: Linear amino-acid sequence.
  • Secondary: $\alpha$-helices, $\beta$-sheets via hydrogen bonding.
  • Tertiary: 3-D folding driven by hydrophobic interactions, ionic bonds, disulfide bridges.
  • Quaternary: Multi-subunit assembly (e.g. hemoglobin = $\alpha<em>2\beta</em>2$).
• Glycogen
  • Branched polymer of $\alpha$-1→4-linked glucose with $\alpha$-1→6 branches every ~8–12 residues; stored in liver & skeletal muscle for rapid glucose mobilization.
  • Enzymes: Glycogen synthase (formation), glycogen phosphorylase (breakdown).
  • Hormonal regulation: Glucagon/epinephrine stimulate breakdown; insulin promotes synthesis.