Kidney Function & Osmoregulation – Vocabulary Review

Core Concept: Homeostasis

• Goal: maintain constant internal conditions (temperature, pH, osmotic pressure, ion balance, nutrient levels, waste removal).
• Benefits
  • Enzymes work at optimum conditions → maximal metabolic efficiency.
  • Protects proteins/membranes from denaturation.
  • Allows organisms to function across wider external environments without performance loss.
  • Reduces energy spent on corrective processes (e.g.
    shivering, panting).

Excretion vs Osmoregulation

• Excretion: removal of toxic metabolic wastes (mainly nitrogenous) from body fluids.
  • Mammalian main waste = urea.
• Osmoregulation: regulation of osmotic concentration (water : solute ratio) of body fluids.
  • Expressed in \text{osmol\;L}^{-1} (or \text{mOsmol\;kg}^{-1} in physiology).
  • Primarily performed by the kidneys.
• Distinction
  • Excretion eliminates molecules; osmoregulation may conserve or discard water/ions without necessarily removing toxins.

Nitrogenous Wastes Across Taxa

• Ammonia (NH₃) produced by deamination is highly toxic, requires abundant water to dilute.
• Conversion pathways (energy trade-off vs. water saving):
  • Aquatic animals: excrete NH_3 directly into water.
  • Mammals: convert to urea (moderate toxicity, moderate energy cost, water soluble).
  • Birds & many reptiles: convert to uric acid (non-water-soluble, high energy cost, minimal water loss → lighter for flight).

Kidney Gross Anatomy

• Each kidney supplied by renal artery, drained by renal vein.
• Ureter conveys urine → bladder → urethra → exterior.
• Regions
  • Cortex: outer; site of ultrafiltration & fine adjustment.
  • Medulla: inner; site of osmotic gradient & bulk water reabsorption.
  • Renal pelvis: collects urine before ureter.

Nephron – Functional Unit

• Millions per kidney; all drain into ureter.
• Major parts (cortex → medulla → cortex route):
  • Bowman's capsule & glomerulus (ultrafiltration).
  • Proximal convoluted tubule (PCT) (selective reabsorption).
  • Loop of Henle – descending & ascending limbs (counter-current multiplier for water conservation).
  • Distal convoluted tubule (DCT) (fine ion & pH regulation).
  • Collecting duct (final water reabsorption; site of ADH action).
• Associated vessels
  • Afferent arteriole → glomerulus → efferent arteriole.
  • Peritubular capillaries surround PCT & DCT.
  • Vasa recta (counter-current blood flow paralleling loop of Henle).

Ultrafiltration (Glomerulus & Bowman's Capsule)

• Blood arrives via wide afferent arteriole, leaves via narrow efferent arteriole → high hydrostatic pressure.
• Structures enabling filtration (size cut-off <65\,000\ \text{amu}):
  • Fenestrated endothelium (≈100\ \text{nm} pores) holds back cells.
  • Basement membrane (negatively-charged glycoprotein mesh) excludes plasma proteins.
  • Podocytes with foot processes & filtration slits further limit passage.
• Produces glomerular filtrate (water, ions, glucose, amino acids, urea, small peptides, HCO₃⁻, etc.)
• Daily formation: 1{-}1.5\ \text{L} urine from ~180\ \text{L} filtrate → ∼45\ \text{g} solute (≈30\ \text{g} urea + 15\ \text{g} NaCl).

Selective Reabsorption (Proximal Convoluted Tubule)

• Filtrate initially contains glucose, amino acids, vitamins, hormones, Na^+, Cl^-, urea, water.
• PCT epithelial adaptations:
  • Microvilli → huge surface area.
  • Many mitochondria → ATP for active transport.
  • Basal membrane invaginations → shorten diffusion distance.
• Transport mechanisms
  • Na^+: pumped into interstitial fluid by Na^+/K^+-ATPase; drives secondary transport.
  • Glucose & amino acids: co-transported with Na^+, then diffuse into blood.
  • Cl^-: follows electrochemical gradient (facilitated & active).
  • Water: osmosis following solute removal.
  • Urea: some passive diffusion.
• Quantities
  • ~1.5\ \text{kg} salt & 5.5\ \text{kg} glucose filtered daily; ~100 % reclaimed here in healthy person.

Loop of Henle – Countercurrent Multiplier

• Purpose: generate high osmotic gradient in medulla to conserve water.
• Descending limb
  • Permeable to water, impermeable to ions.
  • Water exits → filtrate becomes hypertonic.
• Ascending limb
  • Thin lower section: passive Na^+, Cl^- diffusion out.
  • Thick upper section: active transport of Na^+, Cl^- to medulla; impermeable to water.
• Result: medullary interstitial fluid reaches >1200\ \text{mOsm}, creating gradient for collecting duct.
• Countercurrent nature: filtrate flows opposite directions; at each horizontal level, descending limb fluid slightly more concentrated than ascending limb fluid → multiplier effect.

Distal Convoluted Tubule (Fine Adjustment)

• Regulates:
  • pH: secretes H^+ / NH3, reabsorbs HCO3^-.
  • Ions: variable reabsorption of Na^+/Cl^-; secretion of K^+ under aldosterone control.
  • Water: permeable; amount reabsorbed depends partly on ADH.

Collecting Duct – ADH-Mediated Osmoregulation

• Passes through high-osmolar medulla → water potential gradient favors water exit.
• Antidiuretic hormone (ADH)
  • Synthesised in hypothalamus; stored/released by posterior pituitary.
  • Osmoreceptors detect plasma osmolarity.
  • When dehydrated (↑ plasma osmolality), ADH release increases.
  • ADH triggers insertion of aquaporins into collecting-duct membrane → ↑ water permeability.
  • Outcome: more water reabsorbed, urine volume ↓, concentration ↑ (anti-diuresis).
• If hydrated → ↓ ADH → fewer aquaporins → dilute urine.
• Typical human plasma range influencing thirst & ADH: 280{-}320\ \text{mOsmol\ kg}^{-1}.

Quantitative Relationships & Example Questions

• Percentage change formula: \frac{\text{new} - \text{old}}{\text{old}} \times 100\%.
• Predicted ADH at 300\ \text{mOsmol\ kg}^{-1} (from trend): ~9{-}10\ \text{pmol\ dm}^{-3}.
• Drinking to satiety → plasma osmolarity ↓ toward 280\ \text{mOsmol\ kg}^{-1}; ADH falls; thirst quenched.
• Causes of ↑ plasma osmolarity: sweating, high salt intake, diarrhea, inadequate water intake.

Relationship: Medulla Thickness vs. Urine Concentration

• Relative medullary thickness (RMT) strongly correlates with maximum solute concentration (MSC) of urine.
  • Desert rodents (e.g.
    Eligmodontia typus, RMT 11.4) achieve MSC >8{,}600\ \text{mOsm}.
• Thicker medulla → longer loops of Henle → larger gradient → more water conservation.

Filtration, Reabsorption & Excretion Fractions

• Daily filtration vs. excretion (approx.):
  • Water: >99\% reabsorbed (only \approx1\% excreted).
  • Glucose: \approx100\% reabsorbed; 0\% excreted in healthy state.
  • Urea: ~50\% reabsorbed, 50\% excreted.
  • Na^+ / Cl^-: ~99.5\% reabsorbed; 0.5\% excreted.
  • Proteins/peptides: normally \approx100\% retained in blood (should not appear in filtrate).

Regulation of Renal Blood Flow

• Vasoconstriction / vasodilation of afferent & efferent arterioles adjust glomerular filtration rate.
• Systemic activity changes (sleep, exercise):
  • During vigorous activity: ↑ skeletal muscle flow, ↓ gut & kidney flow (but kidney must remain fairly constant for waste removal → autoregulation mechanisms).
  • Piglet study: asleep vs. awake shows organ-specific redistribution; in piglets kidney flow unchanged whereas in adult humans it often decreases during sleep (species difference in developmental needs & thermoregulation).

Clinical & Real-World Connections

• Glucosuria indicates PCT saturation → diagnostic for diabetes mellitus.
• Loop diuretics (e.g.
  furosemide) inhibit Na^+ reabsorption in ascending limb → ↑ urine volume.
• ADH analogues treat diabetes insipidus; ADH antagonists manage hyponatremia.
• Desert mammal kidney morphology inspires water-saving technologies (biomimicry).
• Ethical consideration: water availability & renal disease management in low-resource settings.

Key Equations & Values Recap

• Osmotic concentration unit: 1\ \text{osmol\ L}^{-1} = 1\ \text{mol\ of\ osmotically\ active\ particles\ per\ litre}.
• Pressure driving ultrafiltration: glomerular capillary pressure ≈55\ \text{mmHg} minus opposing forces.
• Daily filtrate: \approx180\ \text{L}; daily urine: 1{-}1.5\ \text{L}.
• Threshold MW for filtration: <65{,}000\ \text{amu}.
• Counter-current gradient: medullary interstitium from cortex (~300\ \text{mOsm}) to inner medulla (>1200\ \text{mOsm}).

Study Checklist

• [ ] Define and contrast excretion & osmoregulation.
• [ ] Identify anatomical parts of kidney & nephron.
• [ ] Explain mechanisms of ultrafiltration & selective reabsorption with structural adaptations.
• [ ] Describe countercurrent multiplier in loop of Henle.
• [ ] Explain ADH control of collecting duct permeability.
• [ ] Interpret data linking medulla thickness, urine concentration, ADH vs. plasma osmolarity.
• [ ] Calculate percentage change & solute balances.
• [ ] Relate blood flow redistribution to physiological states.