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CNS Physiology - Grand Viva Q&A

(Guyton & Hall - South Asia Edition)

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SECTION 1: ORGANIZATION OF THE NERVOUS SYSTEM & SYNAPSES

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1. Spinal cord level - Generates walking movements, controls local blood flow, peristalsis, urination, etc.
2. Lower brain (subcortical) level - Controls subconscious activities like blood pressure, respiration, equilibrium, feeding responses, emotional reactions
3. Higher brain (cortical) level - Enables thought, language, memory, and precise voluntary movements

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• Determining the direction of signal transmission
• Selectively blocking weak signals while allowing strong signals to pass
• Amplifying certain signals and channeling them in multiple directions
• Some synapses facilitated by prior use (basis of memory)

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• A presynaptic terminal (also called terminal knob, bouton, end-foot, synaptic knob) is separated from the postsynaptic neuron by a synaptic cleft of 200-300 Angstroms (Å)
• The presynaptic terminal contains two key structures: transmitter vesicles (containing neurotransmitter) and mitochondria (supplying ATP for neurotransmitter synthesis)
• On an anterior motor neuron: 10,000-200,000 presynaptic terminals on its surface; 80-95% on dendrites, only 5-20% on the soma

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• The presynaptic membrane contains active zones where vesicles are docked
• Docking occurs via SNARE proteins: vesicle SNARE (synaptobrevin / v-SNARE) binds to membrane target SNAREs (syntaxin and SNAP-25 / t-SNAREs)
• Arrival of an action potential causes calcium ion influx into the terminal
• Calcium triggers vesicle fusion with the membrane and release of transmitter into the cleft
• The key phrase: "No calcium - no transmitter release"

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• EPSP (Excitatory Postsynaptic Potential): Transmitter opens sodium channels → Na+ influx → membrane depolarizes → neuron more likely to fire
• IPSP (Inhibitory Postsynaptic Potential): Transmitter opens K+ or Cl- channels → K+ leaves or Cl- enters → membrane hyperpolarizes → neuron less likely to fire
• EPSPs and IPSPs summate algebraically at the axon hillock; if the net effect reaches threshold, an action potential fires

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SECTION 2: SENSORY RECEPTORS AND SENSORY PROCESSING

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1. Mechanoreceptors - touch, pressure, stretch (e.g., Pacinian corpuscles, Meissner's corpuscles)
2. Thermoreceptors - cold and warm receptors
3. Nociceptors - pain receptors
4. Photoreceptors - rods and cones in the retina
5. Chemoreceptors - taste, smell, O2/CO2 in blood
6. Osmoreceptors - osmolality detection

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• Mechanical compression deforms the terminal fiber
• This opens ion channels, allowing Na+ to diffuse inward
• The Na+ influx creates a local depolarization = receptor potential
• This local current spreads to the first node of Ranvier inside the capsule
• At the node, it triggers a full action potential that propagates to the CNS
• Receptor potential magnitude increases with stimulus strength but in a non-linear (logarithmic-like) manner - allows sensitivity at low intensities yet prevents saturation at high intensities

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• Rapidly adapting (phasic) receptors: Pacinian corpuscles (adapt in milliseconds), hair receptors (within seconds) - signal "change" in stimulus
• Slowly adapting (tonic) receptors: Joint capsule receptors, muscle spindles, baroreceptors (may take 2 days) - signal "ongoing" stimulus
• Significance: allows the nervous system to focus on changes rather than constant, unchanging stimuli

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SECTION 3: SPINAL CORD REFLEXES

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• Stimulated when a muscle is suddenly stretched
• Receptor: Muscle spindle (nuclear bag and nuclear chain fibers innervated by Ia afferents)
• Pathway: Ia afferent → directly synapse on alpha motor neuron (monosynaptic) → muscle contracts
• Function: Opposes change in muscle length; maintains posture
• Example: Knee jerk (patellar reflex) - tapping patellar tendon stretches quadriceps → reflex contraction

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• Triggered by a painful stimulus
• Causes withdrawal of the limb from the stimulus
• Polysynaptic - involves multiple interneurons
• Has afterdischarge (continued contraction after stimulus removed) due to reverberating circuits among interneurons
• More interneurons = longer latency but also longer afterdischarge

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• Occurs 0.2-0.5 seconds after a flexor reflex is initiated on one limb
• The opposite limb extends to support body weight while the pained limb withdraws
• Signals cross to the opposite side of the cord to excite extensor muscles
• Long latency (200-500 ms) confirms many interneurons are involved
• Has an even longer afterdischarge than the flexor reflex
• Purpose: push entire body away from painful stimulus

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• When one muscle group is excited, the antagonist is simultaneously inhibited
• Example: When stretch reflex activates a flexor, the extensor is inhibited via interneurons releasing inhibitory neurotransmitters
• The neuronal circuit causing this is called reciprocal innervation
• The phenomenon is called reciprocal inhibition
• This prevents opposing muscles from fighting each other and allows smooth coordinated movement

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• Follows complete transection of the spinal cord
• All spinal cord functions below the lesion are completely suppressed (flaccid paralysis, loss of reflexes, loss of autonomic functions)
• Duration: minutes in frogs, weeks in primates, 2+ weeks in humans
• Recovery: Reflexes gradually return (often hyperreflexia due to loss of descending inhibition); autonomic dysreflexia may develop
• Cause: Loss of descending facilitatory signals (especially from corticospinal and reticulospinal tracts) that normally keep the cord slightly excited

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• Located in parallel with extrafusal muscle fibers
• Contains intrafusal fibers: nuclear bag fibers (detect dynamic changes) and nuclear chain fibers (detect static length)
• Innervated by:
  • Ia (primary) afferents - from both bag and chain fibers, respond to rate of stretch AND steady stretch
  • II (secondary) afferents - mainly from chain fibers, respond to steady stretch only
• The intrafusal fibers are also contractile via gamma motor neurons; gamma activation keeps spindle sensitive even when the muscle shortens (alpha-gamma co-activation)

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SECTION 4: MOTOR CORTEX AND CORTICOSPINAL TRACT

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• Located in the precentral gyrus (Brodmann area 4), anterior to the central sulcus
• Has a somatotopic (homuncular) organization - the motor homunculus
• Areas controlling skilled, fine movements (hand, fingers, face) are disproportionately large
• The cortex is activated by signals from: somatosensory cortex (parietal), thalamus (VL nucleus), basal ganglia, and cerebellum

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• Located anterior to the primary motor cortex
• Stores "motor programs" - learned complex sequences of movements
• Sends signals to the primary motor cortex to initiate specific movements
• Also sends fibers directly to the spinal cord (contributing to the corticospinal tract)

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• Located on the medial surface of the cerebral hemisphere, anterior to the primary motor cortex
• Functions in programming sequences of movements and is active during mental rehearsal of movement (even without actual movement)
• Works in parallel with the premotor area

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• Originates from the motor cortex, premotor area, and supplementary motor area
• Contains >1 million fibers per tract
• Betz cells (giant pyramidal neurons in primary motor cortex) give rise to the largest fibers (~16 micrometers diameter), only ~34,000 per tract (only 3% of total)
• These Betz cell fibers transmit impulses at ~70 m/sec - fastest signals from brain to cord
• The remaining 97% are fibers <4 micrometers, transmitting background tonic signals
• Descends through internal capsule → cerebral peduncles → pons → decussates at pyramids of medulla → lateral corticospinal tract in cord
• A small uncrossed portion forms the anterior corticospinal tract

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• Found only in the primary motor cortex
• ~60 micrometers in diameter - the largest neurons in the CNS
• Their axons are the fastest-conducting fibers to the spinal cord (70 m/sec)
• Their collaterals loop back to inhibit adjacent cortical areas → "sharpens" the excitatory signal boundaries
• Only ~34,000 Betz cell fibers per corticospinal tract despite >1 million total fibers

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• Upper motor neuron (UMN) lesion signs:
  • Contralateral spastic paralysis (or paresis)
  • Loss of fine voluntary movements (especially fingers)
  • Babinski sign positive (upward toe response on plantar stimulation)
  • Hyperreflexia
  • No muscle atrophy (anterior horn cells and muscles intact)
  • Increased tone (clasp-knife spasticity)

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SECTION 5: CEREBELLUM

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1. Vermis (central strip) - controls axial muscles (neck, trunk, shoulders, hips) and coordinates walking and other gross body movements
2. Intermediate zone of hemisphere - controls distal limb muscles, especially hands, fingers, feet, toes
3. Lateral zone of hemisphere - works with cerebral cortex in planning and timing sequential motor movements; without it, movements become uncoordinated and lose timing

• Anterior lobe
• Posterior lobe
• Flocculonodular lobe (oldest, works with vestibular system for equilibrium)

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1. Fastigial nucleus - receives from vermis; projects to vestibular nuclei and reticular formation → controls posture and equilibrium
2. Interposed nuclei (globose + emboliform) - receive from intermediate zone; project to red nucleus (rubrospinal tract) → controls distal limb movements
3. Dentate nucleus (largest) - receives from lateral hemisphere; projects via superior cerebellar peduncle to VL thalamus → motor cortex → planning of voluntary movements

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• Receives a "forward copy" (efference copy) of intended movement from motor cortex
• Simultaneously receives sensory feedback about actual movement
• Compares the two and sends corrective signals back to motor cortex via thalamus
• Functions: Coordination, timing, smooth execution of movements; maintaining equilibrium; motor learning
• It does NOT initiate movement - it only fine-tunes ongoing movement

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• Ataxia - incoordination of movements
• Dysmetria - inability to judge distance (past-pointing)
• Dysdiadochokinesia - inability to perform rapid alternating movements
• Intention tremor - tremor that worsens as the hand approaches a target
• Nystagmus - due to flocculonodular lobe involvement
• Hypotonia - reduced muscle tone
• Staccato/scanning speech - due to poor coordination of speech muscles
• Romberg negative (ataxia worse with eyes open, unlike sensory ataxia)

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SECTION 6: BASAL GANGLIA

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• Striatum = Caudate nucleus + Putamen
• Globus pallidus (internal and external segments - GPi and GPe)
• Subthalamic nucleus (STN)
• Substantia nigra (pars compacta = SNc; pars reticulata = SNr)

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• Works with motor cortex to plan and sequence complex movements
• Particularly important in:
  • Initiating and scaling movement (size/speed)
  • Suppressing unwanted movements
  • Cognitive functions related to movement sequences
• Receives input from entire cortex → processes → outputs via GPi/SNr → thalamus (VA/VL) → premotor and supplementary motor cortex
• Operates via direct pathway (facilitatory) and indirect pathway (inhibitory)

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• The substantia nigra pars compacta (SNc) uses dopamine and projects to the striatum (nigrostriatal pathway)
• Loss of dopaminergic neurons → Parkinson's disease
• Features of Parkinson's: Tremor at rest (pill-rolling, 4-7 Hz), rigidity (cogwheel/lead-pipe), bradykinesia, postural instability (TRAP mnemonic)
• Imbalance: decreased dopamine → direct pathway less active, indirect pathway more active → net inhibition of thalamus → reduced motor cortex activity

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SECTION 7: VESTIBULAR APPARATUS AND EQUILIBRIUM

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• Encased in petrous part of temporal bone (bony labyrinth)
• Membranous labyrinth contains:
  • Utricle and saccule - detect linear acceleration and gravity (static equilibrium)
  • Three semicircular canals (anterior, posterior, lateral) - detect angular acceleration (dynamic equilibrium)
• Maculae of utricle and saccule contain hair cells embedded in a gelatinous layer with statoconia (calcium carbonate crystals, specific gravity 2-3 times that of surrounding fluid)
• Utricle macula is horizontal - detects head tilt when upright
• Saccule macula is vertical - detects head orientation when lying down

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• Each hair cell has ~100 stereocilia plus one kinocilium (the tallest, located to one side)
• Stereocilia are connected to each other by tip links
• When stereocilia bend toward the kinocilium → K+ channels open → depolarization → increased firing
• When bent away from kinocilium → hyperpolarization → decreased firing
• This directionality allows the vestibular system to detect the direction of head movement/tilt

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• Each canal has a crista ampullaris at its ampulla containing hair cells with a cupula (gelatinous mass without statoconia)
• When the head rotates, endolymph tends to remain stationary (inertia) while the canal rotates with the head → endolymph flow relative to canal
• This flow deflects the cupula → bends hair cells → generates nerve impulses
• The three canals are oriented in three perpendicular planes → detect rotation in any direction

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SECTION 8: CEREBRAL CORTEX AND HIGHER FUNCTIONS

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• Primary somatosensory cortex (postcentral gyrus, areas 1, 2, 3) - receives touch, pain, temperature, proprioception; organized somatotopically
• Somatosensory association cortex - integrates different sensory modalities
• Primary visual cortex (area 17, occipital) - basic visual processing
• Primary auditory cortex (temporal gyrus, areas 41, 42)
• Most storage of memory occurs in the cerebral cortex

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• Bundle of nerve fibers connecting the two cerebral hemispheres
• Transmits learned information from one hemisphere to the other
• Motor cortex fibers from one side connect to the corresponding area of the opposite hemisphere via corpus callosum
• Enables coordination of bilateral movements

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• The relay station for almost all sensory information going to the cortex
• VPL (ventroposterolateral nucleus) - relays somatosensory signals from trunk and limbs
• VPM (ventroposteromedial) - face sensation
• VL/VA nuclei - relay motor signals from cerebellum and basal ganglia to motor cortex
• LGN (lateral geniculate nucleus) - visual relay
• MGN (medial geniculate nucleus) - auditory relay
• Pulvinar - association area integration
• Also involved in consciousness and arousal (via intralaminar nuclei)

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• Located in the reticular formation of the brainstem (extending from medulla to thalamus)
• Maintains wakefulness and consciousness
• Receives inputs from all sensory systems
• Projects diffusely to entire cortex via thalamus
• Destruction → permanent coma
• Stimulation → awakening, alertness
• GABA-ergic sleep-active neurons and monoaminergic wake-active neurons operate in opposition to regulate sleep-wake cycles

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SECTION 9: AUTONOMIC NERVOUS SYSTEM

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• Sympathetic: Increases heart rate (positive chronotropy), increases contractility (positive inotropy), increases conduction velocity via beta-1 receptors → NE → cAMP → Ca2+ influx
• Parasympathetic (vagus): Decreases heart rate (negative chronotropy), slows AV conduction via M2 receptors → ACh → Gi protein → decreased cAMP, increased K+ conductance (hyperpolarization)

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• All preganglionic synapses (both sympathetic and parasympathetic): Acetylcholine (nicotinic receptors)
• Parasympathetic postganglionic synapses (effector organ): Acetylcholine (muscarinic receptors)
• Sympathetic postganglionic synapses (most organs): Norepinephrine (alpha/beta adrenergic receptors)
• Exception - sympathetic postganglionic: Sweat glands - ACh (muscarinic); Adrenal medulla - directly innervated by preganglionic, releases epinephrine (80%) and NE (20%) into blood

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SECTION 10: PAIN AND ANALGESIA

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• Fast pain: perceived when finger is pricked
• Slow pain: the continued burning/aching sensation
• Both types: activated by nociceptors (mechanical, thermal, chemical)
• Substance P is the major neurotransmitter for slow pain (C fibers)

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• Proposed by Melzack and Wall
• Substantia gelatinosa (lamina II) of dorsal horn acts as a "gate"
• Large A-beta fibers (touch/pressure) activate inhibitory interneurons → "close the gate" → reduce pain
• Small C/A-delta fibers (pain) inhibit inhibitory interneurons → "open the gate" → increase pain transmission
• Descending control from brainstem can also close the gate
• Clinical application: Transcutaneous electrical nerve stimulation (TENS), spinal cord stimulation

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• Located in the periaqueductal gray (PAG) and periventricular gray areas of brainstem
• Stimulation produces profound analgesia
• Works via release of enkephalins and endorphins (endogenous opioids)
• These bind mu, delta, kappa opioid receptors
• Pathway: PAG → raphe magnus nucleus → releases serotonin → dorsal horn → inhibits pain transmission
• Also: NE-containing fibers from locus coeruleus contribute
• Exogenous opioids (morphine) mimic this system

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SECTION 11: CEREBROSPINAL FLUID (CSF)

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• Produced mainly by choroid plexus (70-80%) in the lateral, 3rd, and 4th ventricles
• Some from brain parenchyma extracellular fluid
• Volume: ~150 mL total; produced at ~500 mL/day (replaced ~3-4 times/day)
• Normal values:
  • Pressure: 60-150 mmH2O (lateral decubitus)
  • Protein: 15-45 mg/dL
  • Glucose: 60-80% of blood glucose
  • Cells: <5 WBC/mm3, no RBCs
  • Color: clear, colorless

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• Formed by tight junctions between cerebral capillary endothelial cells, supported by astrocyte foot processes
• Highly impermeable to ions and large molecules
• Freely crosses: O2, CO2, water, lipid-soluble molecules, glucose (via GLUT-1)
• Does NOT cross: Proteins, most drugs, bacteria, ionized substances
• Absent in: Hypothalamus, area postrema, posterior pituitary, pineal gland (circumventricular organs)
• Significance: Protects brain from toxins/pathogens; relevant to drug design for CNS diseases

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SECTION 12: SLEEP AND WAKEFULNESS

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• Wakefulness: Promoted by norepinephrine (locus coeruleus), serotonin (raphe nuclei), histamine (tuberomammillary nucleus), orexin/hypocretin (lateral hypothalamus), acetylcholine (brainstem)
• NREM sleep: Promoted by GABA and adenosine (accumulates during waking); VLPO nucleus in hypothalamus (GABAergic)
• REM sleep: Promoted by acetylcholine (pontine tegmentum); inhibited by NE and serotonin

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• Disorder of excessive daytime sleepiness with sudden onset of REM sleep
• Features: Sleep attacks, cataplexy (sudden loss of muscle tone triggered by emotion), sleep paralysis, hypnagogic hallucinations
• Caused by loss of orexin (hypocretin)-producing neurons in lateral hypothalamus (autoimmune destruction)
• Low CSF orexin levels are diagnostic

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HIGH-YIELD ONE-LINERS FOR VIVA

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CVS Physiology - Grand Viva Q&A

(Guyton & Hall - South Asia Edition, Pages 127-348)

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SECTION 1: CARDIAC MUSCLE & ACTION POTENTIAL

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• Phase 0 (Rapid depolarization): Fast Na+ channels open → rapid Na+ influx → membrane potential rises from -85 mV to +20 mV
• Phase 1 (Early repolarization): Fast Na+ channels close; transient K+ outflow
• Phase 2 (Plateau): L-type (slow) Ca2+ channels open → Ca2+ influx balances K+ efflux → maintains depolarization; this Ca2+ triggers further Ca2+ release from SR (calcium-induced calcium release); this phase is unique to cardiac muscle
• Phase 3 (Rapid repolarization): Ca2+ channels close; K+ channels open → K+ efflux → repolarization back to -85 mV
• Phase 4 (Resting membrane potential): -85 to -90 mV in ventricular muscle

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• SA node resting potential: -55 to -60 mV
• Ventricular muscle resting potential: -85 to -90 mV
• The lower (less negative) resting potential of SA node is because its membranes are naturally leaky to Na+ and Ca2+; the positive charges of entering ions partially neutralize intracellular negativity
• This leakiness underlies automaticity - the SA node cannot truly "rest" at a stable negative potential; it spontaneously depolarizes

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1. "Funny" current (If): Hyperpolarization-activated Na+ channels open → slow inward Na+ current (called If or pacemaker current)
2. Calcium current: T-type (transient) Ca2+ channels open → small Ca2+ influx
3. Decreased K+ conductance: K+ channels progressively close → less K+ exits → membrane drifts positive

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• The SA node fires fastest → suppresses all lower pacemakers by depolarizing them before they can self-discharge (overdrive suppression)
• SA node is the normal pacemaker of the heart
• If SA node fails, the next fastest takes over (escape rhythm)
• Example: AV node escape at 40-60/min = "junctional rhythm"

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SECTION 2: CONDUCTION SYSTEM

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• SA node: Located in posterolateral wall of right atrium, below SVC opening; 3 mm wide, 15 mm long, 1 mm thick; fibers only 3-5 µm diameter
• Internodal pathways: Anterior, middle, and posterior internodal tracts conduct impulse from SA to AV node
• AV node: Located in posterior septal wall of right atrium, above tricuspid valve; delays impulse by 0.09-0.12 seconds (allows atria to contract and fill ventricles before ventricular systole)
• Bundle of His: Passes through fibrous septum into interventricular septum
• Right and left bundle branches: Travel down either side of the interventricular septum
• Purkinje fibers: Spread beneath the endocardium; conduct at 1.5-4.0 m/sec (the fastest conducting tissue in the heart)
• AV node: slowest conduction (0.02-0.05 m/sec); Purkinje: fastest

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• AV nodal conduction velocity is only 0.02-0.05 m/sec (very slow), creating a delay of about 0.09-0.12 seconds
• This delay allows the atria to fully contract and empty blood into the ventricles before ventricular systole begins
• Without this delay, atria and ventricles would contract simultaneously → less efficient filling → reduced cardiac output
• The AV node also acts as a gatekeeper - limits the ventricular rate in atrial fibrillation/flutter (protects ventricles from excessively fast rates)

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• An accessory conduction pathway (Bundle of Kent) bypasses the AV node and connects atria directly to ventricles
• This pathway has no AV nodal delay → ventricles activated prematurely (pre-excitation)
• ECG: Short PR interval (<0.12 sec), delta wave (slurred upstroke of QRS), widened QRS
• Danger: If atrial fibrillation occurs, the accessory pathway can conduct at very high rates → ventricular fibrillation and sudden death

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SECTION 3: THE CARDIAC CYCLE

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• a wave: Caused by atrial contraction; right atrial pressure rises 4-6 mmHg; left atrial pressure rises 7-8 mmHg
• c wave: Caused by bulging of AV valves back toward atria at the start of ventricular contraction (isovolumetric phase) + slight traction on atrial musculature by contracting ventricles
• v wave: Caused by slow filling of atria from veins while AV valves are closed during ventricular systole; pressure rises gradually

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• EDV (preload): Volume of blood in ventricle at end of diastole = ~130 mL (normal)
• ESV: Volume remaining after ejection = ~60 mL
• Stroke Volume (SV): EDV - ESV = ~70 mL (range 60-80 mL)
• Ejection Fraction (EF): SV/EDV × 100 = 55-70% (normal); <50% = systolic dysfunction
• Formula: Cardiac Output (CO) = SV × HR = 70 mL × 72/min ≈ 5 L/min

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SECTION 4: HEART SOUNDS

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• Physiological splitting: Aortic valve closes before pulmonary during inspiration (increased RV filling delays pulmonary closure) - normal
• Wide fixed splitting: ASD (increased RV volume regardless of respiration)
• Paradoxical (reversed) splitting: LBBB, severe AS (aortic valve closes late)

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SECTION 5: CARDIAC OUTPUT & FRANK-STARLING MECHANISM

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• Cardiac Output (CO): Quantity of blood pumped into aorta per minute = SV × HR
• Normal resting CO: ~5 L/min (5.6 L/min in young men; ~4.9 L/min in women)
• Cardiac Index (CI): CO per square meter of body surface area = CO / BSA
• Normal CI: ~3 L/min/m² (BSA of 70 kg person ≈ 1.7 m²)
• CI peaks at age 10 (~4 L/min/m²) and declines to ~2.4 L/min/m² at age 80

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• Statement: "The heart pumps all the blood that returns to it, as long as the total amount does not exceed the physiological limit."
• Mechanism: As venous return increases → EDV increases → cardiac muscle fibers are stretched → optimal overlap of actin-myosin → greater force of contraction → increased stroke volume
• At the cellular level: Stretch increases Ca2+ sensitivity of troponin and reduces troponin-I inhibition → more cross-bridge formation
• Graphically: As right atrial pressure (preload) increases, cardiac output increases, but only up to a point (cardiac reserve limit)

• In heart failure: Frank-Starling curve is depressed (same preload → less output)
• In exercise: Increased venous return → stretch → greater SV (one component of increased CO)

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• Preload: The degree of myocardial stretch before contraction = EDV; determined by venous return; increased by: fluid overload, increased venous tone
• Afterload: The resistance the ventricle must overcome to eject blood = aortic pressure/TPR; increased by: hypertension, aortic stenosis
• Increased preload → increases SV (Frank-Starling)
• Increased afterload → decreases SV (ventricle works harder for less output); compensated by hypertrophy in chronic states

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1. Nervous stimulation: Sympathetic activation increases both cardiac output curve AND venous return (by constricting veins, raising Psf)
2. Hypertrophy: Physically enlarged heart muscle can pump more; takes weeks to months to develop (e.g., athletes, chronic pressure overload)

• Coronary artery disease / ischemia
• Valvular disease (stenosis/regurgitation)
• Cardiomyopathy
• Cardiac tamponade
• Toxic states (excess K+, severe acidosis)

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• Sympathetic stimulation has a dual effect:
  1. Makes the heart a stronger pump (positive inotropy + chronotropy)
  2. Increases mean systemic filling pressure (Psf) from ~7 mmHg to ~17 mmHg by constricting veins → increases venous return
• Result: Cardiac output can nearly double with maximal sympathetic stimulation
• Conversely, total sympathetic blockade (spinal anesthesia) → CO falls to ~2.5 L/min

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SECTION 6: ELECTROCARDIOGRAM (ECG)

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• Atrial repolarization is not visible - hidden within QRS complex
• T wave occurs 0.25-0.35 sec after QRS
• ECG is composed of both depolarization waves (P, QRS) and repolarization waves (T)

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• Lead I: Right arm (-) to Left arm (+); records lateral heart
• Lead II: Right arm (-) to Left leg (+); records inferior heart; usually tallest P and R waves
• Lead III: Left arm (-) to Left leg (+)
• aVR, aVL, aVF: Augmented unipolar limb leads

• V1-V6 placed on the chest surface; V1-V2 over right ventricle, V3-V4 over septum, V5-V6 over left ventricle

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SECTION 7: BLOOD PRESSURE REGULATION

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• Blood pressure = Cardiac output × Total peripheral resistance
• Normal: 120/80 mmHg (systolic/diastolic)
• Pulse pressure = Systolic - Diastolic = 40 mmHg
• Mean Arterial Pressure (MAP): Diastolic + 1/3 Pulse pressure = 80 + 13 = 93 mmHg (approximately 70-110 mmHg)
• Alternatively: MAP = (Systolic + 2×Diastolic) / 3

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• Baroreceptors: Stretch receptors in carotid sinus (IX nerve - Hering's nerve) and aortic arch (X nerve)
• Activated when BP rises → send signals to cardiovascular centers in medulla (NTS)
• Response to high BP: Inhibit vasomotor center + activate vagal center → reduced sympathetic outflow + increased parasympathetic → vasodilation + decreased HR + decreased contractility → BP falls
• Response to low BP: Decreased baroreceptor firing → sympathetic activation → vasoconstriction + tachycardia → BP rises

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• Increased arterial pressure → increased renal perfusion → increased urine output (pressure diuresis)
• Excess salt/water excreted → reduced blood volume → reduced venous return → reduced CO → BP falls to normal
• Kidneys are the ONLY organ that can provide infinite-gain, long-term BP control
• A damaged or abnormal kidney set-point is the key factor in essential (primary) hypertension

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SECTION 8: RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)

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1. Powerful vasoconstriction (arterioles > venules) → increases TPR → increases BP
2. Aldosterone secretion from adrenal cortex → Na+ and water retention → increased blood volume
3. ADH release from posterior pituitary → water retention
4. Direct renal effects → Na+/water retention
5. Thirst stimulation → increased fluid intake
6. Cardiac hypertrophy (long-term)

1. Decreased renal perfusion pressure (baroreceptors in JG cells)
2. Decreased Na+ delivery to macula densa (distal tubule)
3. Sympathetic stimulation (beta-1 receptors on JG cells)

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• Cause: Adrenal adenoma or hyperplasia → excess aldosterone secretion
• Effects: Increased renal Na+/water reabsorption → increased blood volume → hypertension
• In early stages: increased CO; in later stages: CO normalizes but TPR increases
• Features: Hypertension + hypokalemia + metabolic alkalosis + low renin
• If untreated: Can cause renal damage that perpetuates hypertension even after aldosterone excess is corrected

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SECTION 9: VENOUS RETURN & MEAN SYSTEMIC FILLING PRESSURE

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• Psf is the pressure throughout the circulation if the heart stops and blood redistributes equilibrium throughout all vessels
• Normal Psf = ~7 mmHg
• It represents the "fullness" of the vascular system - determined by blood volume and vascular compliance
• Venous return is driven by the gradient: Psf - Right atrial pressure
• Increased by: Blood transfusion, sympathetic stimulation (venous constriction) - can rise to 17 mmHg with max sympathetic stimulation
• Decreased by: Hemorrhage, acute venous dilation (syncope)

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1. Decreased blood volume (hemorrhage) - most common; insufficient blood to create filling pressure
2. Acute venous dilation - sudden sympathetic withdrawal (fainting/syncope); blood pools in veins
3. Obstruction of large veins - IVC/SVC obstruction
4. Decreased tissue mass (muscle wasting, prolonged inactivity) - reduced metabolic demand and blood flow
5. Decreased metabolic rate - hypothyroidism; reduced tissue O2 demand → reduced blood flow

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SECTION 10: LOCAL CIRCULATION & SPECIAL CIRCULATIONS

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• The ability of an organ to maintain constant blood flow despite changes in perfusion pressure (60-180 mmHg range)
• Mechanisms:
  1. Myogenic: When vessel wall is stretched by increased pressure → smooth muscle contracts (Bayliss effect)
  2. Metabolic: When flow falls → O2↓, CO2↑, adenosine↑, K+↑, pH↓ → vasodilation → flow returns to normal
• Best autoregulation: Kidney, brain, heart
• Poorest autoregulation: Skin, skeletal muscle (at rest)
• Purpose: Protects organ from pressure fluctuations and matches flow to metabolic need

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• Normal coronary flow: 250 mL/min at rest; can increase 4-5 fold during exercise
• Unique feature: Left coronary arteries are compressed during systole → most flow occurs in diastole; right coronary flow occurs throughout cycle
• Primary regulator: Local metabolic factors (adenosine is the most important vasodilator in coronary circulation; also: CO2, K+, lactate, prostaglandins)
• Oxygen extraction: The heart extracts ~70-80% of oxygen from blood at rest (vs. 25% for most tissues) → cannot significantly increase O2 extraction; relies on vasodilation to increase flow when demand rises
• Coronary steal: Vasodilators (e.g., dipyridamole) dilate vessels maximally - collateral vessels may divert blood away from ischemic zones → used in stress testing

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• Normal cerebral blood flow: ~750 mL/min = ~15% of resting CO
• Autoregulates between MAP 60-160 mmHg
• Blood-brain barrier (tight junctions) protects brain from toxins
• Primary regulator: CO2 (most potent cerebral vasodilator); hypercapnia → vasodilation → increased CBF; hypocapnia (hyperventilation) → vasoconstriction → decreased CBF
• Poor sympathetic innervation → spared from sympathetic vasoconstriction during exercise and shock (as mentioned by Guyton)
• Intracranial pressure (ICP): Normal = 7-15 mmHg; CPP (cerebral perfusion pressure) = MAP - ICP; CPP must be ≥50-60 mmHg

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SECTION 11: CARDIAC OUTPUT DURING EXERCISE

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1. Sympathetic nervous system activation:
   • Heart: Increased HR and contractility (positive chronotropy + inotropy)
   • Parasympathetic withdrawal → further HR increase
   • Peripheral vasoconstriction in non-essential organs (skin, gut, kidneys)
   • Exception: Coronary and cerebral vessels have poor vasoconstrictor innervation - spared from constriction
2. Increase in arterial pressure - moderate increase in MAP
3. Increase in cardiac output - can reach 20-25 L/min (4-5× normal) in moderate exercise; up to 40 L/min in elite athletes

• Active skeletal muscle: local metabolic vasodilation → diverts blood to muscles
• Increased venous return (muscle pump, respiratory pump, increased Psf from venous constriction)
• Local vasodilators in muscle: adenosine, CO2, K+, ATP, lactic acid

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• Resting VO2: ~250 mL/min
• Maximal VO2 (VO2 max): 3,500-4,000 mL/min in untrained; up to 6,000+ mL/min in trained athletes
• Fick principle: CO = VO2 / (arterial O2 content - venous O2 content) = VO2 / (a-vO2 difference)
• Normal a-vO2 difference at rest = 50 mL/L blood (5 mL/dL)
• During exercise: a-vO2 difference increases AND CO increases → together increase O2 delivery

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SECTION 12: SHOCK & CIRCULATORY FAILURE

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• Definition: Cardiac output so low that tissue nutrition is inadequate; potentially lethal within minutes to hours
• Types:
  1. Hypovolemic shock: Decreased blood volume (hemorrhage, dehydration, burns)
  2. Cardiogenic shock: Pump failure (MI, tamponade, severe valve disease)
  3. Distributive shock: Maldistribution of blood flow:
     • Septic shock: Bacterial toxins → massive vasodilation + capillary leak
     • Neurogenic (vasogenic) shock: Loss of vasomotor tone (spinal cord injury, deep anesthesia)
     • Anaphylactic shock: Histamine release → vasodilation
  4. Obstructive shock: Physical obstruction (massive PE, tension pneumothorax)

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• Initial insult → decreased CO → decreased tissue perfusion → ischemia
• Ischemia damages capillary endothelium → capillary leak → fluid loss from vessels
• Myocardial ischemia → weaker heart → even less CO
• Acidosis, toxins → vasodilation → venous pooling
• Eventually reaches "irreversible" state where even full resuscitation cannot restore life
• This is an example of positive feedback that Guyton discusses in Chapter 1 as potentially causing "vicious cycles and death"

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HIGH-YIELD ONE-LINERS FOR CVS VIVA

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