Video 2 - Urinary System II – Nephron Function, Filtration Pressures & Hormonal Regulation

Renal Corpuscle & Filtration Membrane

• Review link to Urinary I
  • Filtration occurs exclusively in the renal corpuscle.
  • Secretion + re-absorption occur along the entire nephron.
• Microanatomy (SEM images shown)
  • Glomerulus = ball-of-yarn–like fenestrated capillary bed.
  • Podocytes (“podo” = feet) wrap cellular processes around each capillary → create an extra filtration layer (“double coffee-filter” analogy).
  • Layers of the filtration membrane
  • Fenestrated capillary endothelium (small pores, not sinusoidal).
  • Basement (basal) lamina.
  • Filtration slits formed by interdigitating podocyte foot processes.
  • Glomerular (Bowman’s) capsule = simple squamous epithelium; space between capsule & glomerulus = capsular (Bowman’s) space.
• Functional significance
  • Blood cells & large proteins (e.g., hemoglobin) are too big/charged to cross; their presence in urine ⇒ pathology (proteinuria, hematuria).

Pressures Governing Filtration

• Blood Hydrostatic Pressure (BHP)
  • Created by incoming afferent arteriole (larger) vs. efferent arteriole (smaller).
• Capsular Hydrostatic Pressure (CHP)
  • Pressure from filtrate already present in capsular space pushing back against filtration.
• Colloid Osmotic Pressure (COP)
  • Osmotic pull of plasma proteins draws water back toward blood.
• Net Filtration Pressure (NFP)
  • NFP = BHP - (CHP + COP)
  • Example from lecture: 55\,\text{mmHg} - (15\,\text{mmHg} + 30\,\text{mmHg}) = 10\,\text{mmHg} (filtration proceeds).
  • If systemic BP drops (e.g., BHP ≈ 30 mmHg), NFP can fall to \le 0 → urine production stops (protective in shock/hemorrhage).

Glomerular Filtration Rate (GFR)

• Normal: \approx 100{-}125\,\text{mL min}^{-1}.
• Directly proportional to NFP; small pressure changes cause large GFR changes.

Proximal Convoluted Tubule (PCT)

• Epithelium: simple cuboidal with brush border.
• ~99 % of filtrate reabsorbed here.
  • Water, Na⁺, K⁺, Cl⁻, HCO₃⁻, nutrients (glucose, AA).
• Secretion (blood → tubule)
  • Urea, H⁺, some drugs/toxins.
• Histology tie-in: classic “ring of cubes” seen on Histology lab slides.

Nephron Loop (Loop of Henle)

• Regions & epithelia
  • Thick descending limb → cuboidal.
  • Thin descending limb → thin squamous (very narrow).
  • Thick ascending limb → cuboidal.
• Process: Counter-Current Multiplication (CCM)
  1. Active transport in thick ascending limb pumps Na⁺, K⁺, Cl⁻ into medullary interstitium (uses ATP).
  2. Increased medullary “solute-iness” (hypertonicity) pulls water osmotically from thin descending limb.
  3. Vasa recta capillaries quickly reabsorb water → preserves gradient.
  4. Positive feedback: more salt pumped → more water removed → stronger gradient.
• Purpose: create concentrated medullary interstitium to permit maximal water reabsorption later.

Distal Convoluted Tubule (DCT)

• Functions
  • Secretion (blood → tubule): K⁺, H⁺, drugs, toxins.
  • Reabsorption (tubule → blood): Na⁺, Ca²⁺ (under hormonal control).
• Hormonal links
  • Parathyroid hormone (PTH) ↑ Ca²⁺ reabsorption when serum Ca²⁺ low.
  • Calcitonin can encourage Ca²⁺ loss when serum Ca²⁺ high.
• Structural note: DCT passes between afferent & efferent arterioles forming macula densa.

Collecting Ducts

• Receive filtrate from multiple nephrons.
• Water reabsorption driven by hypertonic medullary interstitium.
• Hormonal regulation
  • Antidiuretic Hormone (ADH)
  • Inserts aquaporin water channels into apical membrane via vesicle fusion.
  • With ADH → small volume, concentrated urine (water retained).
  • Without ADH → large volume, dilute urine (water lost).
  • Aldosterone (from RAAS)
  • ↑ Na⁺ reabsorption in PCT & collecting duct; H₂O follows osmotically.
  • ↑ K⁺ secretion → clinical need for K⁺ supplements in patients with high aldosterone/RAAS activity (common in hypertension).

Juxtaglomerular Apparatus (JGA)

• Components
  • Macula densa (modified DCT cells) – chemo/osmo-sensors.
  • Granular (juxtaglomerular) cells in arteriole walls – baroreceptors, renin secretors (contain cytoplasmic “pepper-like” granules).
• Location: DCT loops back between afferent & efferent arterioles.
• Function
  • Monitor local BP & filtrate osmolarity.
  • Low BP/low NaCl sensed → renin release → activates RAAS → raises systemic BP & blood volume.
• Clinical correlation
  • Paradoxically, essential hypertensive patients often show elevated renin → persistent aldosterone → volume retention & K⁺ wasting.

Hormonal Recap & Integrated Physiology

• ADH (posterior pituitary)
  • Trigger: ↑ plasma osmolarity or ↓ blood volume.
  • Effect: Add aquaporins, conserve H₂O.
• Aldosterone (adrenal cortex)
  • Trigger: Angiotensin II, ↓ Na⁺, ↑ K⁺.
  • Effect: Reabsorb Na⁺/H₂O, secrete K⁺.
• PTH & Calcitonin (calcium balance) act at DCT.
• Safety mechanism: If systemic BP falls so low that BHP < (CHP + COP) → NFP ≤ 0, GFR ≈ 0 → urine formation stops, conserving volume in shock.

Clinical / Ethical / Practical Implications

• Routine urinalysis (protein, blood) screens for filtration-membrane damage.
• Understanding CCM & ADH guides treatment of dehydration vs. water intoxication.
• Diuretic drugs often target Na⁺ transporters or inhibit RAAS to control hypertension; must monitor K⁺ levels.
• Ethical prescribing: weigh benefits (BP control) vs. risk of hypokalemia in elderly (may require supplementation).

Key Numbers & Equations for Quick Review

• Normal GFR: 100{-}125\,\text{mL min}^{-1}.
• NFP equation: NFP = BHP - (CHP + COP).
• Illustrative values
  • Normal: 55 - (15+30) = 10\,\text{mmHg}.
  • Hypotensive example: 30 - (15+30) = -15\,\text{mmHg} → filtration stops.

High-Yield Summary

• Filtration barrier = capillary fenestrations + basement membrane + podocyte slits.
• Three pressures dictate filtration; small shifts can halt urine formation.
• PCT reclaims bulk of filtrate; Loop of Henle establishes gradient; DCT fine-tunes ions; Collecting duct sets final water content (ADH/aldosterone).
• JGA is renal “barometer”; secretes renin → RAAS.
• Hormonal interplay (ADH, aldosterone, PTH, calcitonin) determines final urine volume/composition.
• Pathologies (proteinuria, hypertension, hypokalemia) often trace back to dysfunction in these mechanisms.