Lecture 19: GFR

Human Kidney Physiology: GFR

• Instructor: Dr. James Scholey, Professor of Medicine, University of Toronto
• Key Topics Discussed:
  1. Case of the Day
  2. Vascular Anatomy
  3. Glomerulus: Ultrafiltration
  4. Glomerulus: Perm-selectivity
  5. Measurement in Humans

Case of the Day: Kidney Disease

• Patient Description: 55-year old woman with a history of diabetes mellitus.
• Recent Tests:
  • Serum creatinine: 160 umol/L (normal value: 80 umol/L)
  • 24-hour urine collection: 500 mg albumin detected
• Assessment: Indicates possible kidney dysfunction.

Vascular Anatomy of the Kidney

• The kidneys located retroperitoneally at the lower ribs level.
• Blood Flow Data:
  • Cardiac Output: 5 L/min
  • Renal Blood Flow: 1 L/min
  • Renal Plasma Flow: 500 mL/min
• Body Water Volume:
  • Total body water: 40 L (60% body weight)
  • Extracellular fluid: 15 L (20% body weight)

Glomerulus Functions

• Ultrafiltration Mechanism:
  • Utilizes Starling Forces:
  • Glomerular Capillary Pressure ($P_{GC}$)
  • Tubular Hydrostatic Pressure ($P_{T}$)
  • Oncotic Pressure ($\boldsymbol{ ext{Π}}_{A}$)
  • Ultrafiltration Coefficient ($K_f$)
  • Plasma Flow ($Q_A$)

Glomerular Pressure Dynamics:

• Pressures:
  • $P_{GC}$ approximately 50 mm Hg
  • $P_{T}$ at 10 mm Hg
  • Oncotic Pressure between $20-25$ mm Hg

Glomerular Filtration Rate (GFR)

• Definition: The volume of fluid filtered from the kidney glomerular capillaries into Bowman's capsule per unit time.
• Normal GFR: 95-120 ml/min, with overall filtration around 150-170 L/day.

Determinants of GFR

• GFR mainly influenced by renal blood flow, affected by:
  • Arterial Pressure: High arterial BP increases GFR
  • Renal Vascular Resistance: Myogenic reflex regulates afferent arterioles
• Autoregulation:
  • Blood flow constant between 70 to 150 mmHg.
  • If BP decreases, afferent arterioles dilate.
  • If BP increases, afferent arterioles constrict.

Ultrafiltration Characteristics

• Starling Forces determine movement:
  • High hydraulic conductivity of glomerular capillaries leads to efficient filtration.
• Capillary Mechanics:
  • Ultrafiltration reduces with increased oncotic pressure of plasma ($\boldsymbol{P}<em>{GC} - P</em>T - \boldsymbol{Π}_{GC}$).

Filtration of Solutes

• Small Solutes: Freely filtered through the glomerulus (examples: sodium, potassium).
• Macromolecules (protein filtration):
  • Depends on molecular weight and charge; albumin (68kDa) is minimally filtered.
• Permselectivity ensures larger molecules remain in the bloodstream while small solutes pass into urine.

Why Measure GFR?

• GFR is critical for evaluating kidney health since it correlates with kidney disease.
• Measuring Techniques:
  • Use of inulin for precise GFR measure.
  • More commonly, serum and urine creatinine levels estimate GFR; creatinine clearance formula:
    $ext{Creatinine Clearance} = \frac{V}{P} imes [U]<em>{creat}$ where V = urine flow rate, $[U]{creat} = $ urine creatinine concentration, $P = $ plasma creatinine concentration.

Summary of Key Concepts

• Renal blood flow is vital (20-25% of cardiac output).
• GFR depends on blood flow and Starling Forces.
• The glomerulus acts as a barrier to macromolecules while facilitating small solute filtration.