relate the detailed structure of the Bowman’s capsule and proximal convoluted tubule to their functions in the formation of urine

Cambridge International AS & A Level Biology – Topic 8: Transport in Mammals

Learning Objectives

• Describe the detailed structure and function of the mammalian circulatory system (heart, blood vessels, blood).
• Explain how oxygen and carbon‑dioxide are transported in the blood (haemoglobin, Bohr & Haldane shifts, chloride shift).
• Relate the detailed structure of Bowman's capsule and the proximal convoluted tubule (PCT) to their roles in urine formation.
• Integrate renal processes with systemic circulation to show how homeostasis is maintained.
• Plan, carry out and evaluate investigations related to blood pressure, heart rate and renal function (AO3).

1. Overview – How the Three Systems Interact

Transport in mammals links three inter‑related systems:

• Cardiovascular system – pumps blood, provides the transport medium.
• Respiratory gas exchange – loads O₂ onto haemoglobin and removes CO₂.
• Renal system – filters plasma, re‑absorbs needed substances and excretes waste.

All three rely on the same fundamental principles of diffusion, bulk flow, active transport and membrane permeability (AO1, AO2).

2. The Circulatory System

2.1 The Heart – Structure & Function

• Four chambers: two atria (receive) and two ventricles (pump).
• Valves prevent back‑flow:

  • Atrioventricular (tricuspid & mitral) – between atria and ventricles.
  • Semilunar (pulmonary & aortic) – at the bases of the pulmonary artery and aorta.

• Wall layers (inside → out):

  1. Endocardium – simple squamous epithelium.
  2. Myocardium – thick striated cardiac muscle (site of contraction).
  3. Pericardium – fibrous sac with serous layers.

• Cardiac output (CO) – the volume of blood the heart pumps per minute:

  CO = HR × SV

  where HR = heart rate (beats min⁻¹) and SV = stroke volume (mL beat⁻¹). CO determines the delivery of O₂ and nutrients to tissues and the perfusion pressure that drives glomerular filtration.

• Blood pressure – generated by cardiac output and peripheral resistance; measured as systolic/diastolic (mm Hg). It is a key regulator of GFR (see Section 4).

2.2 Cardiac Cycle & Electrical Conduction

• Systole – ventricular contraction ejects blood into the pulmonary artery and aorta.
• Diastole – ventricular relaxation allows chambers to fill from the atria.
• Electrical sequence:

  1. SA node (pacemaker) initiates the impulse → atrial contraction.
  2. AV node delays the impulse → ensures complete ventricular filling.
  3. Bundle of His → right & left bundle branches → Purkinje fibres spread the impulse through ventricular myocardium.

• Modulation of heart rate:

  • Autonomic nervous system – sympathetic ↑HR, parasympathetic ↓HR.
  • Hormones – adrenaline ↑HR; atrial natriuretic peptide (ANP) ↓HR.

2.3 Blood Vessels – Three‑Layer Model & Functions

2.4 Blood Composition

• Plasma (≈55 % of blood volume) – water, electrolytes, plasma proteins (albumin, globulins, fibrinogen), nutrients, hormones, waste products.
• Formed elements (≈45 %) – red blood cells (RBCs), white blood cells (WBCs), platelets.
• RBCs contain haemoglobin (Hb), the principal carrier of O₂ and CO₂.

3. Transport of Oxygen and Carbon‑Dioxide

3.1 Haemoglobin Structure & Cooperative Binding

• Tetrameric protein (α₂β₂); each subunit binds one O₂ molecule.
• Co‑operative binding produces a sigmoidal O₂‑dissociation curve.

  • High PO₂ in the lungs → Hb becomes oxy‑haemoglobin.
  • Low PO₂ in tissues → Hb releases O₂.

• Each gram of Hb can bind ≈1.34 mL O₂.

3.2 Bohr & Haldane (Chloride) Shifts

• Bohr effect – ↑CO₂ or ↓pH (↑H⁺) in tissues reduces Hb affinity for O₂, promoting release.
• Haldane effect – O₂ binding to Hb reduces its affinity for CO₂, facilitating CO₂ uptake in the lungs.
• Chloride shift (Hamburger phenomenon) – In systemic capillaries, CO₂ enters RBCs and is hydrated by carbonic anhydrase:

  CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

  HCO₃⁻ leaves the cell in exchange for Cl⁻ (via the AE1 exchanger), maintaining electrical neutrality.

3.3 Overall CO₂ Transport Pathways

1. ~70 % as bicarbonate ions (HCO₃⁻) in plasma.
2. ~23 % bound to haemoglobin as carbamino‑haemoglobin.
3. ~7 % dissolved directly in plasma.

4. The Renal System – From Filtration to Reabsorption

4.1 Bowman's Capsule – Detailed Structure & Filtration Mechanism

• Parietal layer – simple squamous epithelium forming the outer capsule wall.
• Visceral layer (podocytes) – specialised epithelial cells with interdigitating foot processes (pedicels) that create filtration slits bridged by slit diaphragms.
• Glomerular capillaries – high‑pressure, fenestrated capillary tuft surrounded by podocytes.
• Bowman's space (capsular lumen) – collects the primary filtrate.

Ultrafiltration is driven by the net filtration pressure (NFP):

NFP = P_GC – P_BS – π_GC

and the glomerular filtration rate (GFR):

GFR = K_f × NFP

where K_f = filtration coefficient (permeability × surface area).

4.2 Proximal Convoluted Tubule (PCT) – Detailed Structure

• Simple cuboidal epithelium with a dense apical brush border (microvilli) – surface area ≈ 20–30 µm² per cell.
• Abundant mitochondria – supply ATP for Na⁺/K⁺‑ATPase and secondary active transport.
• Basolateral infoldings contain transport proteins:

  • Na⁺/K⁺‑ATPase (primary active).
  • Na⁺/glucose cotransporter (SGLT1).
  • Na⁺/H⁺ exchanger (NHE3).
  • Na⁺/amino‑acid cotransporters.

• Close association with peritubular capillaries & vasa recta – creates a counter‑current exchange system that rapidly returns reabsorbed solutes to the circulation.

4.3 Functional Highlights of the PCT

1. Reabsorption (≈ 65 % of filtered load)

   • Na⁺ – primary active transport creates an electrochemical gradient.
   • Water – follows Na⁺ osmotically through aquaporin‑1 (AQP1) channels.
   • Glucose & amino acids – secondary active via Na⁺‑dependent cotransporters.
   • HCO₃⁻ – reclaimed by converting filtered H⁺ (secreted via NHE3) to CO₂, then back to HCO₃⁻ (via carbonic anhydrase) and transported into the interstitium.

2. Secretion – organic acids (e.g., uric acid), drugs, excess K⁺ and H⁺ are actively secreted into the lumen.
3. Acid‑base balance – net reabsorption of HCO₃⁻ and secretion of H⁺ maintain plasma pH (~7.4).

4.4 Representative Transport Equations

Primary active Na⁺ transport (Na⁺/K⁺‑ATPase):

J_{Na⁺}^{active} = P_Na⁺ × ([Na⁺]_interstitium – [Na⁺]_lumen)

Secondary active glucose reabsorption (SGLT1):

J_glucose = T_max ×

\frac{[Na⁺]{lumen}[glucose]{lumen}}{K{m,Na}[Na⁺]{lumen}+K{m,glc}[glucose]{lumen}+[Na⁺]{lumen}[glucose]{lumen}}

5. Integration – Maintaining Homeostasis

• Blood pumped from the left ventricle → systemic capillaries → delivers O₂ (bound to Hb) and picks up CO₂ and metabolic wastes.
• ~20 % of cardiac output reaches the renal glomeruli, providing the hydrostatic pressure needed for filtration.
• Reabsorbed solutes (Na⁺, glucose, HCO₃⁻) re‑enter the peritubular capillaries, returning to the systemic circulation and influencing plasma osmolarity and acid‑base status.
• Kidney‑derived hormones (renin, erythropoietin, ANP) feed back to the heart and vasculature, regulating blood pressure, blood volume and red‑cell mass.

6. Clinical Correlations

• Glomerulonephritis – inflammation damages podocyte slit diaphragms → proteinuria, oedema.
• Acute tubular necrosis (ATN) – loss of PCT brush border → reduced reabsorption → glucosuria, electrolyte disturbances.
• Heart failure – ↓ cardiac output reduces renal perfusion → activation of the renin‑angiotensin‑aldosterone system (RAAS) → Na⁺/water retention.
• Chronic obstructive pulmonary disease (COPD) – chronic hypercapnia shifts the O₂‑dissociation curve rightward (Bohr effect), impairing tissue oxygenation.

7. Practical Skills (AO3) – Suggested Investigations

1. Pulse and Heart‑Rate Monitoring

   • Measure resting pulse, then after graded exercise.
   • Analyse % increase, recovery time, and relate to fitness level.

2. Blood Pressure Using a Sphygmomanometer

   • Determine systolic and diastolic pressures in supine, sitting and standing positions.
   • Discuss baroreceptor reflexes and autonomic regulation.

3. Effect of Caffeine on Heart Rate

   • Record baseline heart rate, ingest a standard caffeine dose, re‑measure at 15‑min intervals.
   • Evaluate experimental error, control variables, and draw conclusions about sympathetic stimulation.

4. In‑Vitro Filtration Model (Simulating GFR)

   • Use a semi‑permeable membrane, apply controlled hydrostatic pressure, and measure filtrate volume.
   • Vary pressure to illustrate the relationship GFR = K_f × NFP.

8. Assessment Objective (AO) Mapping

9. Summary Table – Structure ↔ Function (Nephron & Cardiovascular Highlights)