describe the roles of the hypothalamus, posterior pituitary gland, antidiuretic hormone (ADH), aquaporins and collecting ducts in osmoregulation

Homeostasis in Mammals – Overview (Cambridge syllabus 14.2)

How the Note Meets the Assessment Objectives

Major Homeostatic Systems (Syllabus 14.2)

1. Blood‑Glucose Regulation

• Key organs: Pancreatic β‑cells (insulin) and α‑cells (glucagon).
• Set‑point: ~5 mmol L⁻¹ (≈90 mg dL⁻¹) fasting blood glucose.
• Negative‑feedback loop:

  1. ↑ plasma glucose → β‑cells depolarise → Ca²⁺ influx → insulin release.
  2. Insulin stimulates GLUT4 translocation in muscle/adipose, glycogen synthesis in liver and inhibits hepatic gluconeogenesis.
  3. ↓ plasma glucose → reduced insulin & ↑ glucagon from α‑cells.
  4. Glucagon stimulates hepatic glycogenolysis and gluconeogenesis, raising glucose.

• Clinical links:

  • Type 1 diabetes – autoimmune destruction of β‑cells → absolute insulin deficiency.
  • Type 2 diabetes – insulin resistance + relative insulin deficiency.

2. Thermoregulation

• Control centre: Pre‑optic/anterior hypothalamus (POAH) – detects skin & core temperature via thermoreceptors.
• Effectors (cold‑defence):

  • Shivering – rapid skeletal‑muscle contraction (via somatic nerves).
  • Non‑shivering thermogenesis – brown‑adipose UCP1 activity (stimulated by sympathetic norepinephrine).
  • Vasoconstriction – reduces cutaneous blood flow, conserving heat.

• Effectors (heat‑defence):

  • Sweating – eccrine glands release water; evaporation removes heat.
  • Vasodilation – increases skin blood flow, promoting heat loss.

• Feedback: POAH integrates temperature signals, sends autonomic outputs (sympathetic/parasympathetic) to effectors; when temperature returns to set‑point, signals cease.
• Exam tip: Remember to mention both neural (hypothalamic) and hormonal (thyroid hormones, epinephrine) contributions.

3. Calcium Balance

• Key hormones:

  • Parathyroid hormone (PTH) – released when plasma Ca²⁺ falls.
  • Calcitonin – released from thyroid C‑cells when Ca²⁺ rises.
  • 1,25‑dihydroxy‑vitamin D (calcitriol) – enhances intestinal Ca²⁺ absorption.

• Target organs & actions:

  • Bone: PTH stimulates osteoclast‑mediated resorption; calcitonin promotes osteoblast activity.
  • Kidney: PTH increases Ca²⁺ re‑absorption (distal tubule) and reduces phosphate re‑absorption; vitamin D raises both Ca²⁺ and PO₄³⁻ re‑absorption.
  • Intestine: Vitamin D up‑regulates Ca²⁺ channels (TRPV6) and binding protein (calbindin).

• Set‑point: ~2.2–2.6 mmol L⁻¹ (9–10.5 mg dL⁻¹) ionised calcium.
• Clinical links:

  • Hyperparathyroidism – ↑ PTH → hypercalcaemia, kidney stones.
  • Hypoparathyroidism – ↓ PTH → hypocalcaemia, tetany.

4. Osmoregulation (Focus of the Original Note)

4.1. Core Loop – Hypothalamus → ADH → Kidney

• Hypothalamic osmoreceptors (antero‑lateral hypothalamus) – neurones that swell when plasma osmolality rises (≈ 285–295 mOsm kg⁻¹). Firing frequency is the primary signal for ADH release.
• Posterior pituitary (neurohypophysis) – stores ADH synthesised in the supra‑optic nuclei and releases it into the systemic circulation when stimulated.
• Antidiuretic hormone (ADH, vasopressin) – peptide hormone that increases water permeability of the collecting‑duct epithelium.
• V₂ receptors – Gₛ‑protein‑coupled receptors on the basolateral membrane of principal cells in the collecting duct.
• Aquaporin‑2 (AQP2) channels – water‑specific channels inserted into the apical membrane in response to ADH‑stimulated cAMP.
• Collecting ducts (cortical & medullary) – final nephron segment where urine volume and concentration are fine‑tuned.
• Renal medullary gradient (counter‑current multiplication) – steep osmotic gradient (up to ≈ 1200 mOsm kg⁻¹) generated by the loop of Henle, vasa recta and urea recycling; provides the driving force for water re‑absorption.

4.2. Step‑by‑Step Sequence (AO2)

1. Detection: ↑ plasma osmolality → osmoreceptor neurones swell → increased firing.
2. Neural transmission: Action potentials travel down the hypothalamo‑hypophyseal tract to the posterior pituitary.
3. ADH release: Posterior pituitary secretes ADH; threshold ≈ 285 mOsm kg⁻¹, steep rise above ≈ 295 mOsm kg⁻¹.
4. Receptor activation: ADH binds V₂ receptors on basolateral membrane of principal cells.
5. Signal transduction: V₂ → Gₛ → adenylate cyclase → ↑ cAMP.
6. Channel insertion: cAMP activates PKA, phosphorylating AQP2‑containing vesicles; they fuse with the apical membrane, markedly raising water permeability.
7. Signal termination: Phosphodiesterases hydrolyse cAMP; when ADH falls, AQP2 channels are endocytosed.
8. Water movement: Water follows its water‑potential gradient (Ψw) from lumen (higher Ψw) into hyper‑osmotic medullary interstitium (lower Ψw) through AQP2.
9. Urine concentration: Re‑absorbed water returns to circulation, reducing urine volume and increasing solute concentration; plasma volume and osmolality move toward the set‑point.
10. Feedback: When osmolality normalises, osmoreceptor firing declines, ADH secretion falls, and water re‑absorption diminishes.

4.3. Supporting Mechanisms (AO3)

• Thirst centre (antero‑lateral hypothalamus) – activated by the same osmoreceptors; generates the conscious urge to drink, providing an additional route to restore plasma volume.
• Renin‑Angiotensin‑Aldosterone System (RAAS) – low arterial pressure or ↓ Na⁺ delivery to the macula densa → renin release → Ang II → aldosterone secretion → Na⁺ (and water) re‑absorption in the distal tubule and collecting duct, complementing ADH.
• Autonomic innervation of the kidney – sympathetic nerves cause vasoconstriction of afferent arterioles, reducing GFR and limiting water loss during severe dehydration.

4.4. Water‑Potential Terminology (Cambridge emphasis)

• Ψw = Ψs + Ψp (solute + pressure components).
• In the medulla, high solute concentration (high Ψs) makes Ψw very low, pulling water out of the collecting‑duct lumen.

4.5. Pathological States (AO3)

• Diabetes insipidus (DI)

  • Central DI – insufficient ADH production (damage to hypothalamus or posterior pituitary). Dilute, large‑volume urine; risk of dehydration.
  • Nephrogenic DI – renal insensitivity to ADH (defective V₂ receptors or AQP2). Similar phenotype despite normal ADH levels.

• Syndrome of Inappropriate ADH secretion (SIADH) – excessive ADH release → water overload, hyponatraemia, low urine output.
• Effect of ADH antagonists (e.g., conivaptan) – block V₂ receptors → rapid diuresis, useful in hyponatraemic emergencies.

Summary Table of All Four Homeostatic Systems

Link to Other Syllabus Topics

• Transport in mammals (Topic 7) – diffusion of gases, osmosis of water, and active transport of ions underpin all four homeostatic loops.
• Circulatory system (Topic 8) – blood flow delivers hormones, removes waste, and provides the medium for osmotic gradients.
• Kidney structure (Topic 9) – detailed knowledge of nephron segments is essential for understanding the counter‑current multiplication system.

Suggested Diagram

Common Cambridge‑style Examination Questions (AO1‑AO3)

• Explain how plasma osmolality is sensed by hypothalamic osmoreceptors and how this information is transmitted to the posterior pituitary.
• Describe the molecular mechanism by which ADH increases water permeability of the collecting duct, including receptor type, second messenger, and signal termination.
• Predict the effect on urine volume, urine concentration and plasma osmolality if ADH secretion is blocked, and relate this to a clinical condition.
• Compare and contrast central and nephrogenic diabetes insipidus in terms of site of defect, expected hormone levels, and laboratory findings.
• Outline the negative‑feedback loop that controls blood glucose, and explain why this loop fails in type 2 diabetes.
• Discuss how the hypothalamic temperature centre integrates skin‑ and core‑temperature information to produce shivering or sweating.
• Analyse the role of PTH in maintaining plasma calcium concentration and predict the consequences of its excess.

Mastering the sequence of events, the signalling pathways, and the way each system integrates with the nervous and endocrine networks will enable students to answer descriptive, analytical and evaluative questions across the full range of Cambridge International AS & A‑Level Biology (9700) exam tasks.