Video 1 - Urinary Physiology – Nephron & Filtration
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)
Active transport in thick ascending limb pumps Na⁺, K⁺, Cl⁻ into medullary interstitium (uses ATP).
Increased medullary “solute-iness” (hypertonicity) pulls water osmotically from thin descending limb.
Vasa recta capillaries quickly reabsorb water → preserves gradient.
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.