Homeostasis, Stress Responses & Adaptive Regulation – Exam Study Notes

Physiology & the Concept of Homeostasis

• Etymology & Scope of Physiology
  • “Physis” = nature | “Logia” = study → physiology = study of the logic of life.
  • Concerned with functions & mechanisms that keep living systems alive, coordinated and adaptive.
• Foundational Figures & Definitions
  • Claude Bernard (1865): “Milieu intérieur” → life requires constancy of the internal environment despite external change.
  • Walter B. Cannon (1932): coined Homeostasis → $\text{Homoios = similar},\; \text{Stasis = standing-still}$.
  • Cannon’s insight: true stability is dynamic—it anticipates disturbance and readies corrective action.
  • Homeostasis ≠ “unchanging” → variables oscillate around a set point within an acceptable range.

Unit Learning Outcomes (PHYS30012)

• Define & explain homeostasis.
• Compare levels of regulation (molecular → behavioural).
• Describe set point operation in normal vs adaptive homeostasis; role of feedback.
• Distinguish stressor vs stress response.
• Summarise three stress-response axes (neural, neuro-endocrine, endocrine) + examples.
• Differentiate autonomic vs automatic actions.
• Explain importance of time course in adaptive responses.

Principles of Homeostatic Control

• Core Features
  • Maintain “normal” condition (set point).
  • Self-regulating via feedback & feed-forward loops.
  • Coordinated, multi-level responses; enable adaptation and survival.
• Levels of Regulation
  1. Molecular/Chemical
  2. Cellular
  3. Tissue
  4. Organ
  5. Organ-system
  6. Whole-organism (behaviour, CNS)
     → Hierarchy allows local fine-tuning plus integrated systemic control.
• Set Point & Acceptable Range
  • Example arterial pressure set point: $\text{MAP}_{\text{set}} \approx 95\;\text{mmHg}$.
  • Deviation triggers compensatory autonomic (↑SNS or ↑PNS) responses.
  • Feedback ON when variable drifts outside range; OFF once variable re-enters band.
• Feed-Forward Anticipation
  • Learned or conditioned responses (e.g., cephalic insulin release, pre-exercise cardiovascular priming) adjust variables before disturbance fully manifests.

Illustrative Example – Glucose Homeostasis

• Classical Endocrine Loop (simplified)
  • Rising plasma glucose → pancreatic β-cells secrete insulin → tissue uptake (GLUT4 translocation) & hepatic glycogenesis → ↓glucose back to \sim90\,\text{mg·dL}^{-1}.
  • Falling glucose → α-cells release glucagon → hepatic glycogenolysis/gluconeogenesis → ↑glucose.
  • Negative feedback around the set point.
• Expanded, Multi-level Control
  • Behaviour/environment: feeding behaviour, digestion, intestinal absorption.
  • Muscular: exercise-induced, insulin-independent GLUT4 recruitment.
  • Central: limbic reward pathways, hypothalamic appetite centres modulate intake & satiety.
  • Intracellular β-cell signalling:
  – Glucose uptake (GLUT2/GK) → ↑ATP/ADP → closure of $\text{K}_{\text{ATP}}$ channels → Ca²⁺ influx → insulin exocytosis.
  – Modulators: GLP-1/cAMP-PKA pathway; leptin via STAT3; metabolic coupling factors (malonyl-CoA, glutamate).
• Pathology vs Adaptation
  • Short-lived excursions are adaptive.
  • Chronic dysregulation → diabetes mellitus (set point shift + impaired feedback).

Cardiovascular Example – Mean Arterial Pressure (MAP)

• Determinants: $MAP = CO \times TPR$ where $CO = HR \times SV$.
• Effector Variables
  • HR & SV (cardiac) – chiefly SNS vs PNS modulation.
  • TPR – arteriolar tone via SNS, vasoactive hormones (angiotensin II, vasopressin, epinephrine), local metabolites.
  • Blood volume & viscosity (renal salt/water balance, erythrocyte count).
• Baroreflex sets moment-to-moment adjustments; resetting during exercise widens operating range (adaptive homeostasis).

Stress: Concept & Taxonomy

• Hans Selye’s Definition: “non-specific body response to any demand.”
• Terminology
  • Stressor = stimulus (physical, psychological, environmental, biogenic).
  • Stress response = physiological & behavioural changes elicited.
• Types of Stress
  • Psychological (exams, fear).
  • Physiological (hypoxia, hemorrhage).
  • Environmental (temperature extremes).
  • Biogenic (caffeine, toxins).
• Eustress vs Distress
  • Yerkes-Dodson curve: moderate stress → peak performance; too low/high → sub-optimal.
  • Cognitive appraisal (primary/secondary) dictates whether stressor is perceived as challenge (growth) or threat (harm).

Tripartite Stress-Response Axes & Time Courses

1 Neural Axis – Autonomic vs Automatic

• Autonomic Nervous System (ANS)
  • Involuntary; cannot consciously override (e.g., baroreflex).
  • Divisions: Sympathetic (fight/flight) vs Parasympathetic (rest/digest).
  • Rapid, short-lived neurotransmission.
• Automatic (Habitual) Actions
  • Motor programmes executed without attention (walking, typing).
  • Somatic nerves; can be voluntarily modulated.
• Stress-Evoked SNS Outflow
  • Central origins: hypothalamus (paraventricular nucleus, dorsomedial nucleus), rostroventrolateral medulla (RVLM), raphe nuclei etc.
  • Effector consequences: vasoconstriction, tachycardia, ↑contractility, bronchodilation, diaphoresis, piloerection, glycogenolysis, inhibition of GI motility.

2 Neuro-Endocrine Axis – Sympatho-Adrenal Medulla (SAM)

• Sympathetic pre-ganglionic fibres synapse on adrenal chromaffin cells (modified neurons).
• Catecholamine Biosynthesis & Release
  • $Tyrosine \rightarrow DOPA \rightarrow Dopamine \rightarrow Noradrenaline \rightarrow Adrenaline$.
  • Secretion latency ~20–30 s post-stressor.
• Physiological Actions of Adrenaline/Noradrenaline
  • Cardiovascular: ↑HR, ↑SV, vasoconstriction (α₁), vasodilation in skeletal muscle (β₂).
  • Metabolic: hepatic glycogenolysis, lipolysis, ↑plasma glucose.
  • Respiratory: bronchodilation.
  • Pupillary dilation, sweating.

3 Endocrine Axis – Hypothalamic-Pituitary-Adrenal Cortex (HPA/HPAC)

• Sequence: Stress → PVN neurons secrete CRH & AVP → anterior pituitary releases ACTH via long portal vessels → adrenal cortex (zona fasciculata) secretes cortisol (humans) / corticosterone (rodents).
• Feedback Loops
  • Cortisol exerts negative feedback at hypothalamus & pituitary; regulates circadian variation (SCN input).
• Systemic Effects of Glucocorticoids
  • Metabolic: gluconeogenesis, protein catabolism, adipose lipolysis.
  • Cardiovascular: permissive ↑vascular reactivity to catecholamines.
  • Immune: dose-dependent immunosuppression (lymphocyte apoptosis, ↓cytokines).
  • CNS: mood, cognition modulation.

Neuro-Immune Crosstalk

• Sympathetic fibres innervate spleen, thymus, lymph nodes, bone marrow.
• Catecholamines can enhance (lymphopoiesis, mobilisation) or suppress immunity depending on timing & concentration (Bellinger et al., 2006).
• Corticosterone/cortisol generally suppresses immune function (Frachimont 2006).
• Stress outcome therefore context- & duration-dependent.

Adaptive Homeostasis & Set-Point Plasticity

• Definition (Davies 2016): “Transient expansion/ contraction of homeostatic range after exposure to sub-toxic, non-damaging stimuli.”
• Examples
  • Baroreceptor reflex reset upward during exercise → tolerate higher MAP without triggering reflex bradycardia.
  • Exercise training increases insulin sensitivity; baseline glucose set point unchanged but operational window widens.
  • Heat acclimation: ↓core temp set point, ↑sweat rate.
• Operational Adjustments handle mild, short-term perturbations without structural remodelling.

Time Course, Adaptation vs Maladaptation

• Temporal Matching of response to challenge is critical (Martin 2009).
  • Acute threat → neural & SAM axes dominate.
  • Prolonged challenge (fasting, endurance exercise) → HPA & metabolic hormones.
• Maladaptation / Allostatic Load
  • Persistent SNS activation → hypertension, insulin resistance, cardiomyopathy.
  • Chronic HPA activation → visceral obesity, immune suppression, mood disorders.

Ethical & Practical Considerations

• Recognition that sustained stress responses cause disease mandates workplace, societal, and clinical interventions.
• Stress-modulating therapies (CBT, exercise, pharmacology) aim to restore adaptive homeostasis and prevent pathology.

Numerical / Statistical References

• Normal fasting blood glucose ≈ 90\,\text{mg·100 mL}^{-1} (5 mM).
• Resting MAP ≈ $95\,\text{mmHg}$; acceptable range ± ~15 mmHg.
• Catecholamine ratio: Adrenaline ~80 % | Noradrenaline ~20 % of adrenal medullary output.
• Finometer dataset example: \text{MAP}=87 \text{mmHg},\; HR=67 \text{b·min}^{-1},\; SV=91 \text{mL},\; CO=6.1 \text{L·min}^{-1}.

Key Take-Home Messages

1. Homeostasis is dynamic, not static; variables continually fluctuate within tight limits.
2. Regulation is hierarchical—molecules, cells, organs, systems, behaviour—providing redundancy and precision.
3. Set points can shift (adaptive homeostasis) and operational ranges broaden or narrow in response to challenges.
4. Three stress axes differ in onset & duration: neural (ms-s), neuro-endocrine (s-min), endocrine (min-hours).
5. Duration & intensity of stressor dictate whether response is beneficial (adaptation/eustress) or harmful (maladaptation/distress).
6. Chronic dysregulation (SNS or HPA over-activity) underlies many modern pathologies → imperative to manage stress for health.