JW

D3.3 Homeostasis and Human Physiology

Homeostasis: Core Principles

  • Definition: Ability of an organism to maintain a constant internal environment (steady-state) at preset values despite external fluctuations.

    • Alternative wording: Keeping internal variables within narrow limits.

  • Key human homeostatic variables (all controlled chiefly by negative feedback):

    • Body temperature (core ≈ 37\,^{\circ}\text{C})
    • Blood pH (arterial ≈ 7.35{-}7.45)
    • Blood glucose concentration (set point ≈ 90\,\text{mg}/100\,\text{mL} ≈ 5\,\text{mmol}\,\text{L}^{-1})
    • Blood osmotic concentration / water content
    • Partial pressures of respiratory gases: p\text{CO}2 and p\text{O}2
    • Blood pressure (arterial)
    • Heart rate
    • Concentration of essential ions (e.g.
      \text{Na}^+, \text{K}^+, \text{Ca}^{2+}, \text{Cl}^-)

  • Benefits to organisms:

    • Enzyme-catalysed reactions run at optimal rate (temperature/pH sensitive).
    • Stable internal milieu enables survival in fluctuating external conditions (e.g.
      terrestrial life, seasonal changes).
    • Protects proteins & cell structures from denaturation or osmotic damage.
    • Ensures adequate ATP production and efficient nutrient/gas exchange.

Negative vs. Positive Feedback

  • Feedback loop: control mechanism using information about the outcome to adjust the process.
  • Negative feedback (predominant in homeostasis)
    • Detects deviation above or below set point → triggers responses that counteract change → variable returns to set point.
    • Requires metabolic energy (e.g. ATP for active transport, muscle contraction, sweating).
    • Examples: thermoregulation, blood glucose control, blood pressure regulation, osmoregulation.
  • Positive feedback (rare; amplifies change, drives system away from starting state)
    • Examples in humans: LH/FSH surge during ovulation, oxytocin release during labour, platelet plug formation in clotting.
    • NOT suited for continual regulation; ends in definitive event or external termination.

Blood Glucose Regulation (Endocrine Control Example)

Pancreatic Anatomy & Function

  • Islets of Langerhans (endocrine clusters) embedded in largely exocrine pancreas.
    • \alpha-cells → secrete glucagon.
    • \beta-cells → secrete insulin.
  • Endocrine gland: releases hormones directly into bloodstream (e.g. pancreas islets, hypothalamus, pituitary, ovaries/testes).
  • Exocrine gland: releases products via ducts to epithelial surface (e.g. pancreatic digestive enzymes, sweat, saliva).

Set Point & Perturbations

  • Normal fasting level: \approx90\,\text{mg}/100\,\text{mL}.
  • Hyperglycaemia situations: post-prandial high-carb meal, stress hormones, untreated diabetes.
  • Hypoglycaemia situations: prolonged fasting, intense exercise, excess insulin dose.
  • Note: Persistently high glucose raises blood osmolarity → pulls water out of cells → increases blood volume & blood pressure.

Hormonal Actions

  1. INSULIN (secreted when glucose is high)
    • Stimulates GLUT4 transporter insertion in muscle & adipose membranes → increased facilitated diffusion of glucose.
    • Enhances glycogenesis in liver & skeletal muscle: \text{glucose}\xrightarrow[enzyme]{ATP}\text{glycogen}.
    • Promotes lipogenesis and protein synthesis; inhibits gluconeogenesis & glycogenolysis.
  2. GLUCAGON (secreted when glucose is low)
    • In liver (primary target): stimulates glycogenolysis and gluconeogenesis.
    • Mobilises fatty acids from adipose tissue.
    • Result: raises blood glucose back to set point.

Integrated Negative-Feedback Loop

  • Deviation sensed by \alpha/\beta cells → hormone release → blood transport → receptors on target tissues → metabolic response → plasma glucose returns to set value → hormone secretion falls (self-limiting).

Glucose Tolerance Test (Diagnostic Data)

  • Patient ingests measured glucose bolus; blood glucose logged over hours.
  • Normal curve: modest peak ((<\,180\,\text{mg}/100\,\text{mL})), returns to baseline within \approx2 h.
  • Diabetic curve: higher fasting baseline, sharper peak, takes > 2 h to return, or fails to return.
  • Predictions: Diabetic individual will also show elevated fasting glucose in overnight fast.

Diabetes Mellitus

Shared Features

  • Chronic hyperglycaemia → glucose in urine (exceeds renal threshold), polyuria, polydipsia, polyphagia, weight loss.
  • Long-term complications: nephropathy, neuropathy, retinopathy, cardiovascular disease, poor wound healing.

Type I (Early-Onset / Insulin-Dependent)

  • Cause: Autoimmune destruction of \beta-cells → no/very little insulin.
  • Risk factors: genetics (HLA variants), environmental triggers (viral infection), unexplained autoimmune susceptibility.
  • Usual onset: childhood/adolescence.
  • Symptoms: severe & rapid, ketoacidosis risk.
  • Treatment:
    • Lifelong insulin injections/pump (before meals to match glucose spike).
    • Blood glucose monitoring, balanced diet, exercise.
    • Emerging: islet transplantation, immunotherapy.

Type II (Late-Onset / Insulin-Resistant)

  • Cause: Target cells have defective insulin receptors/GLUT transporters ± reduced insulin secretion.
  • Risk factors: obesity, sedentary lifestyle, high-sugar/fat diet, aging, genetics affecting energy metabolism.
  • Onset: adulthood (increasingly adolescents).
  • Symptoms: mild, fatigue, slow healing; often detected via routine screening.
  • Treatment hierarchy:
    1. Lifestyle change (weight loss, diet with low glycaemic index, exercise).
    2. Oral hypoglycaemics (metformin, sulfonylureas, SGLT2 inhibitors).
    3. Insulin therapy if pancreatic output declines.

Thermoregulation

Sensors & Integrator

  • Peripheral thermoreceptors: skin; detect external temperature.
  • Central thermoreceptors: hypothalamus & body core (spinal cord, viscera).
  • Hypothalamic thermoregulatory centre integrates signals → compares with set point.

Effectors & Mechanisms (Humans)

  • Cooling responses (core >\text{set point}):
    • Vasodilation of cutaneous arterioles → blood flows near surface → heat loss via conduction, convection, radiation.
    • Sweating: eccrine glands secrete water + solutes; evaporation requires breaking H-bonds (endothermic) → removes latent heat.
    • Behavioural adaptations: seeking shade, removing clothing, drinking water.
  • Heating responses (core

Hormonal (Longer-Term) Modulation

  • Thyroxin (T4) increases basal metabolic rate (BMR), thereby raising heat production.
    • Regulation pathway: \text{Hypothalamus}\xrightarrow{TRH}\text{Pituitary}\xrightarrow{TSH}\text{Thyroid}\xrightarrow{T4}.
    • Target tissues: muscle, liver, brain.
    • Feedback: high T4 inhibits TRH & TSH (classical endocrine negative feedback).
  • Adipose function: white fat = insulation; brown fat = active heat generator.

Heat Production & Distribution

  • Metabolism (heart, kidneys, lungs, brain ≈ >70\% of heat output).
  • Blood circulatory system conveys heat from core to periphery.

Comparative Note

  • Birds & mammals share physiological + behavioural thermoregulation; syllabus depth required only for humans.

Ethical & Practical Implications

  • Public‐health importance: rising Type II diabetes prevalence linked to lifestyle → societal costs (healthcare, productivity).
  • Access to insulin & monitoring tech is a global equity issue.
  • Climate change may stress thermoregulation (heatwaves) → emphasises importance of homeostatic understanding in medicine & urban planning.

Key Equations & Figures (LaTeX formatted)

  • Fasting glucose set point: [\text{glucose}]_{plasma}\approx5\,\text{mmol}\,\text{L}^{-1}=90\,\text{mg}\,100\,\text{mL}^{-1}.
  • Thyroxin axis feedback:
    TRH\uparrow\;\Rightarrow\;TSH\uparrow\;\Rightarrow\;T4\uparrow\;\Rightarrow\;BMR\uparrow
    T4\uparrow\;\Rightarrow\;TRH\downarrow,\;TSH\downarrow\;\text{(negative feedback)}

Study Tips & Connections

  • Compare glucose homeostasis with regulation of p\text{CO}_2 (chemoreceptors → medulla → ventilation rate) to reinforce feedback concept.
  • Practise annotating a blank negative-feedback diagram: stimulus → sensor → control centre → effector → response.
  • Work through practice data (glucose tolerance curves) to strengthen graph interpretation skills.
  • Relate BAT uncoupled respiration to oxidative phosphorylation knowledge (ETC & proton gradient).