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Stressor
Stimulus producing a stress response (heat, cold, emotional reaction.)
Cold pressor test (CPT)
Uses nociceptive cold stimulus.
Central Integrator
Hypothalamus initiates the stress response (common to both pathways).
What are the 2 mediated stress response pathways?
Neurally mediated (Sympathetic/sympathoadrenal)
Endocrine-mediated (HPA axis)
What initiates the Neurally-mediated (sympathetic/Sympathoadrenal) pathway ?
The hypothalamus, which activates preganglionic sympathetic neurons that release ACh onto postganglionic neurons and adrenal medulla chromaffin cells.
What does the adrenal medulla release during the sympathetic stress response, and why is it fast?
It releases epinephrine into the bloodstream. It is fast because it is neurally triggered by the preganglionic ACh.
What happens if preganglionic sympathetic ACh release is blocked?
Both NE and Epi release stop, because both pathways depend on the initial cholinergic signal.
What are the major effectors of the neurally mediated stress response?
Heart (contractile + auto-rhythmic cells), smooth muscle of vasculature, pancreas, and other sympathetic targets.
What is the timing difference between the sympathetic response and HPA axis.
Sympathetic: Seconds
HPA axis: minutes to hours
What initiates the endocrine-mediated (HPA axis) stress response?
The hypothalamus releases CRH, which simulates the anterior pituitary.
What hormone does the anterior pituitary release in the HPA axis, what what does it act on?
ACTH, which acts on the adrenal cortex.
What hormone does the adrenal cortex release in the HPA axis, and what is the main role?
Cortisol, which provides sustained metabolic support during stress.
What are the major effects of cortisol?
Increased Gluconeogenesis (liver), Increased protein catabolism (muscle), increased Lipolysis, decreased immune function, and maintains vascular responsiveness to NE/Epi
What structures are involved in the sympathetic vs. HPA stress pathways.
Sympathetic: hypothalamus → Sympathetic NS → Adrenal medulla
HPA: Hypothalamus → Anterior pituitary → Adrenal cortex
Which pathways uses adrenergic receptors, and which uses intracellular steroid receptors?
Adrenergic receptors: Sympathetic (NE/Epi)
Steroid receptors: HPA axis (cortisol)
What neurotransmitter do preganglionic sympathetic neurons release?
ACh
What receptor type does ACh bind to postganglionic sympathetic neurons and adrenal medulla chromaffin cells?
Nicotinic cholinergic receptors (nAChR)
What 2 target cells types express nicotinic ACh receptors int he sympathetic pathway?
Postganglionic sympathetic neurons
Adrenal medulla chromaffin cells
What neurotransmitter do postganglionic sympathetic neurons release?
NE
What does the adrenal medulla release during sympathetic activation?
Epi and some NE(catecholamines)
What receptors types do Epi and NE act on in target tissues?
Adrenergic receptors (alpha and beta)
What is the sequence of hormones in the HPA axis?
CRH → ACTH → Cortisol
What receptors does cortisol bind to in target cells?
Glucocorticoid receptors (intracellular steroid receptors)
Which stress pathway uses neurotransmitters and which uses hormones?
SNS: ACh → NE/Epi (neurotransmitters)
HPA: CRH → ACTH → Cortisol (hormones)
Which pathway is fast and which is slow?
Fast: Sympathetic (seconds)
Slow: HPA axis (minutes-hours)
What receptors mediate the increased heart rate and increased contractility during acute stress?
Beta-1 adrenergic receptors on cardiac contractile and auto-rhythmic cells.
Which organs receive vasodilation during acute stress, and through what receptors?
Heart, skeletal muscle, and liver via beta-2 adrenergic receptors.
Which organs undergo vasoconstriction during acute stress, and through what receptor?
GI tract, Skin, and intestinal blood vessels via alpha-adrenergic receptors.
What is the overall cardiovascular redistribution during fight-or-flight?
Increased blood flow to essential organs (muscle, heart) and decreased blood flow to GI tract and skin.
Why does systolic blood pressure rise later in the stress response?
Because vasoconstriction develops progressively, increasing total peripheral resistance.
What are the major metabolic effects of acute stress?
Mobilization of fuel: Increased glycogenolysis (liver), increased gluconeogenesis (liver), increased lipolysis (adipose), and increased protein catabolism (skeletal muscle).
What is the met metabolic outcome of acute stress?
Increased blood glucose and increased free fatty acids (FFA) for immediate energy.
How does acute stress affect pancreatic hormone secretion?
Decreased insulin and increased glucagon (the “pancreatic tilt”).
How does acute stress affect protein synthesis?
Protein synthesis decreased (shift toward catabolism)
What receptor mediates pupil dilation during acute stress?
Alpha-adrenergic receptors on radial muscle of the iris.
How does acute stress affect GI motility and digestion?
GI motility decreased and digestion is inhibited.
What happens to attention and cognitive altertness during acute stress?
Attention and alertness increase due to NE/Epi effects on the brain.
What happens during alarm phase of GAS?
Immediate SNS activation, catecholamine release, and rising cortisol. Early CPT sign: increased heart rate.
What is the body’s goal during alarm phase?
Provide energy substrates (glucose, FFA) and remove the stressor
What characterizes the resistance phase of GAS?
Coping phase supported by cortisol; performance remains high but at a physiological cost (immune suppression begins).
What symptoms may appear during the resistance phase?
Feeling “on edge”, headaches, irritability, but still functioning.
What defines exhaustion phase of GAS?
Resources depleted, coping capacity exceeded, increased risk of physiological harm.
Give an example of exhaustion phase in real life?
Fatigue and frequent illness during exam week.
What physiological variable is measured with the finger pulse transducer in CPT?
HR
How do you calculate HR in Labchart?
Measure time for 5 cycles, then compute: HR=(Cycles/Time) * 60
How is systolic blood pressure (SBP) measured during CPT?
Using a sphygmomanometer, reading the pressure where Korotkoff sounds first appear as cuff pressure falls.
When should SBP be measured during CPT?
Near the end of the 3-minute immersion, when vasoconstriction is well established.
What statistical test is appropriate for comparing baseline vs. CPT values (HR, SBP, VAS)?
Dependent (paired) t-test
Why is a paired t-test appropriate for CPT data?
Because the same individuals are measured at two time points.
What type of variable was compared in the CPT analysis?
Percent change from baseline.
What is the general formula for percent change?
Percentage change = (CPT-Baseline)/Baseline * 100
What does a positive percent change (ex. +50%) mean?
The dependent variable increased by 50% from baseline.
What does negative percent change (ex, -50%) mean?
The dependent variable decreased by 50% from baseline.
How do you determine whether CPT significantly affected a variable?
Compare the p-value to alpha=0.05
What does it mean if p<0.05 in the CPT analysis?
The change from baseline to CPT is statistically significant.
What does it mean if p > 0.05 in the CPT analysis?
There is no statistically significant difference between baseline and CPT values.
What changes are expected during CPT for VAS, HR, and SBP?
Increased VAS (pain rating), increased heart rate, increased SBP
What is the basic structural organization of skeletal muscle?
Muscle fibers → grouped into fascicles → bundled into whole muscles → attached to skeleton via tendons.
How do skeletal muscle typically work around joints?
Antagonistically-one muscle flexes while the opposing muscle extends (ex. biceps vs. triceps).
What is a motor unit?
A single somatic motor neuron and all the muscle fibers it innervates.
What is the smallest functional unit for muscle contraction?
Motor unit
How does the nervous system increase muscle force?
By recruiting more motor units as load or force demand increases.
Why do small motor units allow for fine control?
Because each motor neuron innervates fewer fibers, allowing precise, graded movements.
What happens when a larger force is required?
Larger motor units with more fibers are recruited to increase total force output.
What determines the strength of a whole-muscle contraction?
The number of active motor units and the frequency of action potentials (rate coding)
What event triggers signaling at the neuromuscular junction?
A motor neuron action potential arriving at the axon terminal.
What ion channels open when the motor neuron AP reaches the terminal?
Voltage-gated Ca2+ channels.
What is the immediate effect of Ca2+ influx into the axon terminal?
Exocytosis of ACh into the synaptic cleft.
What receptors does ACh bind on the muscle fiber?
Nicotinic ACh receptors (nAChR) on the motor end plate.
What type of channel is the nicotinic ACh receptor?
A ligand-gated ion channel (cation channel)
What ions move through nAChR, and which dominantes?
Na+ influx and K+ efflux, with Na+ influx dominating, causing depolarization.
What is the depolarization produced by nAChR activation called?
End plate potential (EPP)
What event directly triggers the muscle action potential?
Opening of nicotinic ACh receptors, which generates a large enough EPP to reach threshold.
Why does opening nAChRs reliably trigger a muscle AP?
Because the EPP is graded but very large, almost always reaching threshold in healthy muscle.
What happens to ACh after it binds its receptors?
It is rapidly broken down by acetylcholinesterase (AChE) in the synaptic cleft.
What event triggers the muscle fiber action potential in E‑C coupling?
The EPP reaching threshold and activating voltage-gated Na+ channels.
Which ion channels open first on the muscle membrane during E‑C coupling?
Voltage‑gated Na⁺ channels, initiating the muscle action potential.
How does the muscle action potential spread through the muscle fiber?
It propagates along the sarcolemma and down the T-tubules.
What receptor acts as the voltage sensor in the T‑tubule membrane?
Dihydropyridine Receptors (DHPR)
How does DHPR activation lead to Ca²⁺ release?
DHPR mechanically opens the Ryanodine Receptor (RyR) on the sarcoplasmic reticulum.
What is the function of the Ryanodine receptor (RYR) in skeletal muscle?
It is a Ca2+ release channel on the sarcoplasmic reticulum.
What protein does Ca²⁺ bind to in order to initiate contraction?
Troponin (specifically Troponin-C)
What is the effect of Ca²⁺ binding to troponin?
The troponin-Ca2+ complex moves tropomyosin, exposing myosin-binding sites on actin.
What happens once tropomyosin is moved off the binding sites?
Myosin heads bind to actin, forming cross‑bridges.
What is the power stroke?
Myosin pulls actin toward the M‑line, producing filament sliding and force generation.
What causes muscle relaxation after contraction?
Ca²⁺ is pumped back into the SR by SERCA pumps, allowing troponin/tropomyosin to re‑block actin.
What happens to tropomyosin during relaxation?
It covers the myosin-binding sites on actin again, preventing cross-bridge formation.
What is recruitment in skeletal muscle?
Increasing the number of active motor units to increase force output.
How does recruitment relate to stimulus intensity in nerve stimulation experiments?
Higher stimulus intensity → more motor units activated until force plateaus when all units are recruited.
What is rate coding (frequency summation)?
Increasing the frequency of action potentials in active motor units to increase force.
Why does higher AP frequency increase force?
Less time for Ca²⁺ reuptake → higher intracellular Ca²⁺ → more cross‑bridges → stronger contraction.
What is a muscle twitch?
A single contraction–relaxation cycle triggered by one action potential.
What is twitch summation?
Additive force when twitches occur before complete relaxation due to excess Ca²⁺ in the cytoplasm.
What causes the “stair‑step” increase in force during summation?
Each stimulus adds more Ca²⁺ before the previous Ca²⁺ is fully cleared, increasing cross‑bridge formation.
What is the freeze response in muscle physiology?
When Ca²⁺ becomes so high that all binding sites are saturated, preventing further changes in force.
What is tetanus (tetanic contraction)?
A sustained contraction caused by high‑frequency stimulation.
What is unfused tetanus?
High‑frequency stimulation with partial relaxation between stimuli; produces a wavy plateau.
What is fused (complete) tetanus?
Very high‑frequency stimulation with no relaxation between stimuli; produces smooth, maximal force.
Which two mechanisms allow the nervous system to modulate muscle force?
Recruitment and rate coding.
What determines muscle force in the length–tension relationship?
The amount of cross‑bridge overlap between actin and myosin.