Glomerular Filtration Physiology 

 1. Anatomy of the Glomerulus

Each nephron contains a glomerulus, which is a tuft of capillaries surrounded by the Bowman’s capsule.

Glomerular Filtration Barrier: 3 Layers

→ Only water and small solutes (<70 kDa) like Na⁺, glucose, urea pass through
→ Proteins and cells are retained in blood (normally no proteinuria or hematuria)

📊 2. Glomerular Filtration Rate (GFR)

GFR = volume of plasma filtered by all nephrons per unit time

• Normal GFR:
• Adults: 90–120 mL/min/1.73 m²
• ~180 L/day of filtrate formed; ~99% is reabsorbed

Clinically important: GFR is a key measure of renal function and used to stage CKD.

⚖️ 3. Starling Forces Governing Filtration

Filtration is determined by net filtration pressure (NFP), derived from Starling’s equation:

NFP=(PGC −PBS )−(πGC −πBS )

Where:

• PGC: Glomerular capillary hydrostatic pressure (~55 mmHg) → Favors filtration
• PBS: Hydrostatic pressure in Bowman’s space (~15 mmHg) → Opposes filtration
• πGC: Oncotic pressure of plasma (~30 mmHg) → Opposes filtration
• πBS: Oncotic pressure in filtrate (~0) → negligible

Net Filtration Pressure ≈ 10 mmHg (favoring filtration)

🎛️ 4. Determinants of GFR

🔁 5. Autoregulation of GFR

Despite systemic BP fluctuations (MAP 80–180 mmHg), GFR remains constant due to autoregulation:

A. Myogenic Mechanism

• ↑ BP → stretch of afferent arteriole → reflex vasoconstriction → protects glomerulus

B. Tubuloglomerular Feedback

• Macula densa senses ↑ NaCl in DCT → afferent vasoconstriction → ↓ GFR

C. RAAS

• Low BP → renin release → angiotensin II → efferent arteriole constriction → ↑ GFR maintained

🧪 6. Measurement of GFR

 Estimated GFR (eGFR): Practical & Common

Estimated from serum creatinine, age, sex, and race using formulas.

A. CKD-EPI Equation (2021 – Preferred)

No longer includes race (which was used in older models)

Formula:
eGFR = 142 × min(Scr/κ, 1)^α × max(Scr/κ, 1)^-1.200 × 0.9938^Age × [1.012 if female]

Where:

• Scr = Serum creatinine (mg/dL)
• κ = 0.7 (female), 0.9 (male)
• α = -0.241 (female), -0.302 (male)

✅ Most accurate across all GFR levels
✅ Used in KDIGO & international guidelines
✅ Built into most lab reporting systems

B. MDRD Equation (Older method)

Less accurate at near-normal GFR (>60 mL/min/1.73 m²)

C. Cockcroft-Gault Equation

Used primarily for drug dosing:

Creatinine clearance = [(140 – age) × weight (kg)] / (72 × serum creatinine)

× 0.85 if female

⚠️ Overestimates GFR in obese/edematous patients (uses body weight)

🧪  Creatinine Clearance (CrCl) – Approximate GFR

Can be measured by:

• 24-hour urine collection
• Serum creatinine

Formula:
CrCl = (Urine creatinine × Urine volume) / Plasma creatinine
(units adjusted to mL/min)

🚫 Errors due to incomplete collection, variability in creatinine secretion

🔬 7. Filtration Fraction (FF)

• ~20% of plasma entering glomerulus is filtered
• Rest continues into peritubular capillaries

Urine Formation: Physiology and Clinical Relevance

Urine formation is a multi-step process by which the kidneys remove waste products and excess substances from the blood while maintaining fluid and electrolyte homeostasis. The process occurs in the nephron, the functional unit of the kidney, and comprises three key steps:

🔁 1. Glomerular Filtration

• Location: Glomerulus → Bowman’s capsule
• Process: Blood plasma (excluding proteins and cells) is filtered into Bowman’s capsule
• Volume: ~180 L/day of filtrate
• Driving Force: Starling forces (hydrostatic > oncotic)
• GFR: ~90–120 mL/min in healthy adults

➡️ Produces an ultrafiltrate similar to plasma but protein-free.

🔄 2. Tubular Reabsorption

The majority of filtrate is reabsorbed into the peritubular capillaries to conserve essential substances.

A. Proximal Convoluted Tubule (PCT)

• Reabsorbs ~65–70% of filtered water, Na⁺, Cl⁻, K⁺, HCO₃⁻, glucose, amino acids
• Glucose reabsorption via SGLT2 transporters (saturated at ~180 mg/dL → glycosuria)
• H⁺ secretion → linked to HCO₃⁻ reabsorption (acid-base balance)

🧠 Clinical relevance: Site of action of carbonic anhydrase inhibitors (e.g., acetazolamide)

B. Loop of Henle

a. Descending Limb

• Highly permeable to water, impermeable to solutes
• Passive water reabsorption → concentrates tubular fluid

b. Ascending Limb (Thick Segment)

• Impermeable to water
• Actively reabsorbs Na⁺, K⁺, 2Cl⁻ (NKCC2 transporter)
• Dilutes tubular fluid (diluting segment)

🧠 Clinical relevance: Loop diuretics (furosemide) inhibit NKCC2 → diuresis

C. Distal Convoluted Tubule (DCT)

• Reabsorbs Na⁺, Cl⁻ via Na⁺/Cl⁻ symporter
• Also reabsorbs Ca²⁺ (under PTH control)
• Impermeable to water

🧠 Clinical relevance: Site of action of thiazide diuretics

D. Collecting Duct

• Final site for water and solute reabsorption
• Controlled by hormones:
• Aldosterone → ↑ Na⁺ reabsorption, ↑ K⁺ & H⁺ secretion
• ADH (vasopressin) → inserts aquaporins → ↑ water reabsorption → concentrates urine

🧠 Clinical relevance:

• SIADH: ↑ ADH → water retention → hyponatremia
• Diabetes insipidus: ↓ ADH or receptor resistance → polyuria, dilute urine

🚽 3. Tubular Secretion

Active transport of substances from peritubular capillaries into tubular lumen.

Common Secreted Substances:

➡️ Plays a vital role in acid-base balance, K⁺ homeostasis, and drug clearance.

📈 4. Final Urine Characteristics

📚 References

• Guyton and Hall Textbook of Medical Physiology
• Brenner & Rector’s The Kidney
• Miller’s Anesthesia
• StatPearls: Renal Physiology
• Oxford Handbook of Nephrology