Ch. 10 The Body in Balance

HOMEOSTASIS – CORE IDEA

• Definition: The tendency of tissues & organ systems to maintain internal balance (equilibrium) despite constantly changing internal/external environments.
  • Requires active, dynamic regulation that keeps cellular milieu within narrow limits.
  • Brain—especially the hypothalamus—plays a pivotal role by:
  • Acting as the master coordinator of internal “clocks.”
  • Regulating hormone secretion via the endocrine & autonomic systems.
• Key processes influenced: nutrient flux, gas/ion exchange, protein synthesis, tissue turnover, waste removal, etc.

CIRCADIAN RHYTHMS

• Periodicity: \approx 24\;\text{hours} (circadian) cycles observed in nearly every cell.
• Cellular clocks:
  • Dictate times to activate, rest, divide.
  • Orchestrate physiological oscillations (e.g., daytime gut peristalsis ↑, nighttime blood pressure ↓).
• Limitation: Peripheral clocks cannot detect daylight → require central synchronizer.

Suprachiasmatic Nucleus (SCN) – MASTER PACEMAKER

• Location: Tiny neuron cluster in hypothalamus, directly above optic chiasm.
• Electrophysiology:
  • Emits steady action-potential stream during day; goes quiet at night.
  • Activity governed by cyclic interaction of two protein sets encoded by “clock genes.”
  • Discovered in fruit fly Drosophila melanogaster; nearly identical genes in mammals.
• Entraining input: Photoreceptor signals from retina keep SCN aligned with Earth’s light–dark cycle.
  • Without light cues, endogenous cycle drifts slightly > 24\;\text{h} (e.g., rhythmic delay in constant darkness experiments).

SCN → BODY PATHWAYS

1. Autonomic neural pathway
   • SCN → Paraventricular Nucleus (PVN) → spinal cord → peripheral organs.
   • Sub-branches regulate orexin neurons (sleep/wake) & other visceral clocks.
2. Hormonal (melatonin) pathway
   • SCN electrical activity → PVN → sympathetic fibers → pineal gland.
   • Pineal gland secretes melatonin into bloodstream at night.
     • Binds widely; reduces alertness/increases sleepiness.
     • Light exposure halts melatonin secretion → promotes wakefulness.

SYSTEMIC SYNCHRONY & EXAMPLES

• Coordinated clocks trigger multi-organ prep for morning:
  • Peak cortisol levels mobilize glucose & raise appetite.
  • Core body temperature rises, boosting metabolic rate.
• Desynchronization consequences:
  • Jet lag, night-shift work, blindness → clocks out of phase with environment.
  • Health risks: weight gain, insomnia, depression, cancers.

NEUROENDOCRINE SYSTEM – BRAIN–HORMONE INTERFACE

• Definition: Brain regions that initiate/control hormone release.
• Hypothalamus–Pituitary Axis (HPA): central node.

Posterior Pituitary (Neurohypophysis)

• Direct axonal release from hypothalamic paraventricular & supraoptic nuclei.
  • Vasopressin (Antidiuretic Hormone, ADH)
    • Kidney water retention ↑, vasoconstriction ↑.
  • Oxytocin
    • Uterine contractions during labor.
    • Milk ejection (let-down) in nursing.

Anterior Pituitary (Adenohypophysis)

• Median eminence capillaries receive hypothalamic releasing/inhibiting hormones → travel short portal vessels → trigger second-tier pituitary hormones.
• Seven anterior-pituitary hormones:
  • Five trophic: target downstream endocrine glands (thyroid, adrenal cortex, gonads, etc.).
  • Two non-endocrine targets:
    • Growth Hormone (GH): bone & soft-tissue growth.
    • Prolactin: breast milk production.
• Functional reach: growth, metabolism, emotion, reproduction, hunger, thirst, stress.

Negative Feedback Loops

• Many pituitary target hormones act back on hypothalamus & pituitary to restrain further release → tight hormonal homeostasis.

REPRODUCTIVE HORMONE CASCADE

1. Hypothalamus releases Gonadotropin-Releasing Hormone (GnRH).
2. Anterior pituitary releases Luteinizing Hormone (LH) & Follicle-Stimulating Hormone (FSH).
3. Gonads secrete sex hormones (testosterone, estrogen, progesterone) & produce gametes.

Male Pattern

• Simple negative feedback → steady \approx 90\text{-min} GnRH pulses maintain relatively constant testosterone, libido, daily sperm production.

Female Pattern (Menstrual Cycle ~ \approx 28\;\text{days})

• Low estrogen/progesterone → FSH ↑ triggers follicle maturation.
• Rising estrogen →
  • Negative feedback on FSH (limits multiple follicles).
  • Positive feedback on LH → LH surge → ovulation.
• Post-ovulation high estrogen/progesterone re-establish negative feedback on GnRH/FSH/LH → ovarian quiet phase → hormone levels fall → cycle restarts.

NON-PITUITARY METABOLIC SIGNALS – LEPTIN & GHRELIN

• Ghrelin
  • Source: Gastric wall when stomach empty.
  • Action: Activates hypothalamic hunger circuits → food-seeking.
  • Stops when stomach full → hunger subsides.
• Leptin
  • Source: Adipocytes (fat cells) proportional to fat stores.
  • Action: Binds hypothalamus; suppresses hunger circuits, stabilizes body weight set-point.
  • Declines with fat loss → increases feeding drive.
• Brain “listens” to these hormones but does not directly regulate their secretion.

STRESS RESPONSE – ACUTE PHASE

• Trigger: Any perceived threat to homeostasis (physical, emotional, internal).

Tri-System Integration

1. Somatic nervous system → skeletal muscles ready for fight-or-flight.
2. Autonomic nervous system
   • Sympathetic branch: Adrenal medulla releases Epinephrine → heart rate ↑, muscle blood flow ↑.
   • Parasympathetic branch: Blood shunted away from skin, gonads, GI tract, kidneys.
3. Neuroendocrine cascade (HPA axis)
   • Hypothalamus releases Corticotropin-Releasing Hormone (CRH).
   • Anterior pituitary releases Adrenocorticotropic Hormone (ACTH).
   • Adrenal cortex releases glucocorticoids (primarily cortisol).

• Glucocorticoid actions:
  • Mobilize glucose from liver, inhibit growth & immunity, sharpen attention & learning centers.

CHRONIC STRESS – PATHOPHYSIOLOGY

• Persistent epinephrine & glucocorticoid elevation → detrimental multi-system effects.

Peripheral Consequences

• Muscle atrophy, visceral fat storage, hyperglycemia → worsened diabetes risk.
• Hypertension & atherosclerosis → higher heart-attack risk.
• Immune suppression → infection vulnerability; potential autoimmune dysregulation.

CNS Consequences

• Hippocampal neurogenesis ↓ → memory formation/recall impaired.
• Cognitive decision pathways suppressed; accelerates age-related decline; amplifies stroke damage.
• Cortisol ↑ delays sleep → insomnia → feedback loop → further cortisol rise.

Developmental & Epigenetic Effects

• Fetal exposure (placental cortisol transfer):
  • Lower birth weight, developmental delay, lifelong hypersensitive stress response.
  • “Thrifty” metabolism predisposes to obesity/diabetes in resource-rich environments.
• Epigenetic inheritance:
  • Chronic stress can modify DNA markers (methylation/acetylation) in germ cells.
  • Potential trans-generational transmission of risk for cancer, obesity, cardiovascular, psychiatric, neurodevelopmental disorders.

REAL-WORLD EXAMPLES & APPLICATIONS

• Jet lag & shift work: illustrate circadian desynchrony → health disturbances.
• Blind individuals: decoupled light cues challenge SCN entrainment.
• Stress in modern contexts (traffic jams, exams, social events) elicits ancient fight-or-flight programming.

ETHICAL & PRACTICAL IMPLICATIONS

• Workplace design: mitigating shift-work impacts on health.
• Maternal care: supporting pregnant women to avoid chronic stress for fetal brain protection.
• Public health: targeting leptin/ghrelin and stress-management pathways in obesity epidemics.
• Potential future therapies: epigenetic editing to reverse stress-induced gene silencing/activation.

KEY TAKEAWAYS (CHEAT-SHEET-STYLE)

• Homeostasis = dynamic equilibrium; hypothalamus is master regulator.
• SCN = central clock; melatonin = nighttime hormone; cortisol = morning readiness signal.
• Hypothalamus → pituitary → peripheral glands = tiered hormone cascades with negative feedback.
• Reproductive feedback: males (simple, steady); females (cyclical, dual feedback) → LH surge drives ovulation.
• Leptin (satiety/fat) vs. ghrelin (hunger/stomach-empty).
• Acute stress = survival advantage; chronic stress = multi-system harm + possible hereditary effects.