Identify, in diagrams, photomicrographs and electron micrographs, the parts of a nephron and its associated blood vessels and structures, limited to: glomerulus, Bowman’s capsule, proximal convoluted tubule, loop of Henle, distal convoluted tubule, c

Topic 14 – Homeostasis (Kidney/Nephron) – Cambridge International AS & A Level Biology (9700)

1. Where this module fits in the syllabus

This note covers the required learning outcomes for Learning Objective 14.1‑14.4 of the Cambridge syllabus:

• LO 14.1 – Identify the parts of a nephron and its associated blood vessels in diagrams, photomicrographs and electron micrographs.
• LO 14.2 – Explain structure‑function relationships of each nephron segment.
• LO 14.3 – Quantitative aspects (e.g., net filtration pressure, GFR, osmotic gradients).
• LO 14.4 – Hormonal regulation of nephron function (ADH, aldosterone, PTH, RAAS, tubuloglomerular feedback).

These concepts link directly to other syllabus topics such as cell structure, membrane transport, enzymes, hormonal control, and the circulatory system.

2. Nephron Overview

The nephron is the functional unit of the mammalian kidney. Each kidney contains ~1 million nephrons, each comprising a vascular component (the glomerulus) and a tubular component that modifies the primary filtrate to produce urine.

3. Glomerulus (LO 14.1, 14.2, 14.3)

3.1 Structure

• Tuft of capillaries arising from the afferent arteriole and draining into the efferent arteriole.
• Three‑layer filtration barrier:

  1. Fenestrated endothelial cells (pores ≈ 70 nm).
  2. Basement membrane – negatively charged, size‑selective.
  3. Visceral layer of Bowman’s capsule – podocytes with interdigitating foot processes and filtration slits (≈ 30 nm).

3.2 Quantitative aspects (LO 14.3)

• Net filtration pressure (NFP) ≈ 10 kPa (≈ 75 mm Hg).
• Glomerular filtration rate (GFR) ≈ 125 mL min⁻¹ (≈ 180 L day⁻¹) in a healthy adult.
• Determinants of NFP:

  • Glomerular capillary hydrostatic pressure ≈ 45 mm Hg.
  • Bowman’s capsule hydrostatic pressure ≈ 15 mm Hg (opposes filtration).
  • Glomerular plasma oncotic pressure ≈ 30 mm Hg (opposes filtration).

• Juxtaglomerular apparatus (JGA) regulates afferent/efferent arteriolar tone → modulates GFR.

3.3 Function

Ultrafiltration of plasma: water, ions, glucose, amino acids and waste products pass; cells and plasma proteins are retained.

4. Bowman’s Capsule (LO 14.1, 14.2)

4.1 Structure

• Visceral layer – podocytes (see above).
• Parietal layer – simple squamous epithelium.
• Bowman’s space (urinary space) – collects primary filtrate before it enters the proximal tubule.

4.2 Electron‑microscopic feature

5. Proximal Convoluted Tubule (PCT) (LO 14.1, 14.2, 14.3)

5.1 Structure

• Broad, highly coiled tube.
• Brush border of dense microvilli (≈ 20 µm long) → surface area ↑ ~30‑fold.
• Abundant mitochondria → supply ATP for Na⁺/K⁺‑ATPase.
• Tight junctions with low paracellular permeability.

5.2 Transport mechanisms

• Active transport – Na⁺/K⁺‑ATPase on basolateral membrane creates an electrochemical gradient used by secondary active cotransporters (Na⁺‑glucose, Na⁺‑amino‑acid).
• Passive diffusion – water follows solutes osmotically via aquaporin‑1 (AQP‑1) channels.
• Secretion – organic acids, drugs and H⁺ via antiporters (e.g., Na⁺/H⁺ exchanger).

5.3 Quantitative re‑absorption (LO 14.3)

• ≈ 65 % of filtered Na⁺, water, K⁺, Cl⁻.
• ≈ 100 % of filtered glucose and amino acids (unless plasma concentration exceeds transport maximum).
• ≈ 85 % of filtered HCO₃⁻ (via Na⁺‑HCO₃⁻ cotransporter).

6. Loop of Henle (LO 14.1, 14.2, 14.3)

6.1 Structure

• Thin descending limb – simple squamous epithelium, high water permeability (AQP‑1), low solute permeability.
• Thin ascending limb – similar epithelium, impermeable to water.
• Thick ascending limb (medullary) – cuboidal cells with abundant mitochondria; active Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2) on apical membrane.

6.2 Counter‑current multiplier (LO 14.3)

1. Descending limb loses water to the hyperosmotic medullary interstitium → filtrate becomes increasingly concentrated.
2. Ascending limb actively pumps Na⁺, K⁺, Cl⁻ out; impermeable to water → filtrate becomes progressively dilute.
3. Vasa recta provide counter‑current exchange, preserving the medullary gradient.

Resulting medullary interstitial osmolarity can reach ≈ 1200 mOsm kg⁻¹ in the inner medulla.

7. Distal Convoluted Tubule (DCT) (LO 14.1, 14.2, 14.4)

7.1 Structure

• Shorter, less convoluted than PCT.
• Fewer microvilli → reduced surface area.
• Presence of hormone‑responsive transport proteins.

7.2 Transport & hormonal control (LO 14.4)

• Na⁺‑Cl⁻ cotransporter (NCC) – reabsorbs ≈ 5‑10 % of filtered NaCl; activity ↑ with aldosterone.
• Ca²⁺ channels (TRPV5) – reabsorption enhanced by parathyroid hormone (PTH).
• H⁺ secretion via H⁺‑ATPase (intercalated cells) – regulated by aldosterone.
• Limited water permeability (no ADH‑dependent aquaporins).

8. Collecting Duct (CD) (LO 14.1, 14.2, 14.4)

8.1 Structure

• Principal cells – Na⁺ reabsorption (ENaC), K⁺ secretion, ADH‑dependent water channels.
• Intercalated cells – acid‑base regulation (α‑type and β‑type, see below).
• ADH‑dependent insertion of aquaporin‑2 (AQP‑2) channels into the apical membrane of principal cells.

8.2 Regulation of water re‑absorption (LO 14.4)

1. Low plasma osmolality → less ADH → AQP‑2 remains intracellular → dilute urine.
2. High plasma osmolality → ADH released → AQP‑2 inserted → water re‑absorbed → concentrated urine.

8.3 Acid–base regulation (LO 14.4)

Intercalated cells fine‑tune systemic pH:

• α‑intercalated cells – secrete H⁺ via apical H⁺‑ATPase and re‑absorb HCO₃⁻ via basolateral Cl⁻/HCO₃⁻ exchanger (AE1). Active when plasma pH is low.
• β‑intercalated cells – secrete HCO₃⁻ via apical Cl⁻/HCO₃⁻ exchanger (pendrin) and re‑absorb H⁺ via basolateral H⁺‑ATPase. Active when plasma pH is high.

9. Tubuloglomerular Feedback (TGF) (LO 14.4)

TGF links tubular NaCl delivery to glomerular filtration rate, providing a rapid intrinsic blood‑pressure control mechanism.

• Macula densa cells (specialised DCT cells) sense NaCl concentration in the distal tubule.
• High NaCl → release of adenosine → constriction of afferent arteriole → ↓ GFR.
• Low NaCl → reduced adenosine, release of nitric oxide & prostaglandins → dilation of afferent arteriole → ↑ GFR.

10. Summary Table of Nephron Segments

11. Key Points for Examination (Cambridge 9700)

1. Label a complete nephron diagram (including afferent/efferent arterioles, Bowman’s capsule, PCT, Loop of Henle, DCT, collecting duct, and associated capillaries).
2. Explain how hydrostatic and oncotic pressures, together with arteriolar tone, determine net filtration pressure and GFR.
3. Describe the counter‑current multiplier in the Loop of Henle and its role in establishing the medullary osmotic gradient.
4. Identify the major transport proteins (Na⁺/K⁺‑ATPase, NKCC2, NCC, ENaC, AQP‑1/2, TRPV5) and state where they are located.
5. Outline tubuloglomerular feedback and how it adjusts GFR in response to distal NaCl delivery.
6. Summarise hormonal regulation:

   • ADH – water permeability of collecting duct (AQP‑2).
   • Aldosterone – Na⁺ re‑absorption (ENaC, NCC) and K⁺ secretion.
   • PTH – Ca²⁺ re‑absorption in DCT.
   • RAAS – afferent/efferent arteriolar tone, Na⁺ re‑absorption.

7. State the actions of α‑ and β‑intercalated cells in the collecting duct for acid‑base balance.