Glomerular Filtration

Glomerular Filtration

Chapter 25

Overview of Urine Formation and Excretion

• Three Processes Involved in Urine Formation:
  1. Glomerular Filtration: Produces a filtrate that is free of cells and proteins.
  2. Tubular Reabsorption: Selectively returns 99% of the substances from the filtrate back to the blood within renal tubules and collecting ducts.
  3. Tubular Secretion: Actively moves substances from the blood into the filtrate within renal tubules and collecting ducts.

Key Renal Processes

• Filtration: Movement of plasma into nephrons.
• Reabsorption: Transfer from renal tubules back to peritubular capillaries.
• Secretion: Transfer from peritubular capillaries into renal tubules.
• Excretion: Final passage of urine from tubules to minor calyces, then to major calyces, renal pelvis, ureter, and bladder.

Detailed Aspects of Glomerular Filtration

• Characteristics of Glomerular Filtrate:
  • Composed mainly of plasma free from proteins and cellular elements.
• Glomerular Filtration Rate (GFR):
  • Defined as the total amount of plasma filtered across all glomeruli in the kidneys per unit time.
  • Influenced by two main factors:
  1. Balance of Hydrostatic and Colloid Osmotic Forces.
  2. Capillary Filtration Coefficient (Kf):
     • Product of the permeability and surface area of the capillaries.

Filtration Membrane and Its Components

• Components of the Filtration Membrane:
  1. Endothelium: Contains thousands of fenestrations (pores).
  2. Basement Membrane: A meshwork of collagen and proteoglycans with significant spaces.
  3. Epithelial Cells: Not continuous; they have long foot-like processes (podocytes) that create filtration slits, separated by slit pores.

Filterability of Solutes

• Table of Filterability:

  Substance	Molecular Weight	Filterability
  Water	18	1.0
  Sodium	23	1.0
  Glucose	180	1.0
  Myoglobin	17,000	0.75
  Albumin	69,000	0.005

• Key Points About Filterability:

  • Inversely related to molecular size; larger substances filter out less effectively.
  • Positively charged molecules filter more readily due to the negative charges present on the filtration barrier.

Clinical Snapshot: Proteinuria

• Definition: Presence of excess protein in urine, indicating possible kidney disease.
• Risk Factors: Includes diabetes, high blood pressure (BP), and family history of kidney disease.
• Symptoms: Frothy, bubbly urine, and swelling in the hands, feet, and face.

Pressures Affecting Filtration

• Forces Promoting Filtration:
  • Hydrostatic Pressure in Glomerular Capillaries: Key driving force for fluid and solute filtration, typically at ~55 mm Hg.
• Forces Inhibiting Filtration:
  1. Hydrostatic Pressure in the Capsular Space: Filtrate pressure in the capsule is ~15 mm Hg.
  2. Colloid Osmotic Pressure in Capillaries: The 'pull' of proteins in the blood averages ~30 mm Hg.

Net Filtration Pressure (NFP)

• Formula for NFP: $ext{NFP} = ext{Outward pressures} - ext{Inward pressures}$$ext{NFP} = ( ext{HP}<em>{gc}) - ( ext{HP}</em>{cs} + ext{OP}_{gc})$ where:
  • $ext{HP}_{gc}$ = Hydrostatic pressure in glomerular capillaries (55 mm Hg)
  • $ext{HP}_{cs}$ = Hydrostatic pressure in capsular space (15 mm Hg)
  • $ext{OP}_{gc}$ = Colloid osmotic pressure in capillaries (30 mm Hg)
• Calculation Example:
  $ext{NFP} = 55 - (15 + 30) = 10 ext{ mm Hg}$

Regulation of GFR (Glomerular Filtration Rate)

• Impact of Pressure Changes:
  • Glomerular hydrostatic pressure adjustments primarily regulate GFR.
• Regulatory Influences:
  • Increased Glomerular Capillary Hydrostatic Pressure increases GFR, while decreased pressures do the opposite.
• Factors Determining Glomerular Hydrostatic Pressure:
  1. Arterial pressure
  2. Afferent arteriolar resistance
  3. Efferent arteriolar resistance

Control Mechanisms of GFR

• Intrinsic Controls (Renal Autoregulation):
  • Maintain a nearly constant GFR when Mean Arterial Pressure (MAP) is between 80-180 mm Hg.
• Extrinsic Controls:
  • Systems maintaining systemic blood pressure, mainly through nervous system and endocrine mechanisms.

Juxtaglomerular Complex (JGC)

• Role:
  • Key in regulating filtrate formation rate and blood pressure.
• Components:
  1. Macula Densa: Chemoreceptors sensing NaCl in the filtrate, located in the ascending limb.
  2. JG Cells: Mechanoreceptors sensing blood pressure in the afferent arteriole.
  3. Mesangial Cells: Functions in contraction and influencing blood flow.

Summary of Autoregulation Mechanisms for GFR

Intrinsic Control (Renal Autoregulation):

• Purpose: Maintain GFR despite blood pressure fluctuations.
• Mechanisms:
  • Myogenic response and Tubuloglomerular feedback.
• Operating Range: Mean arterial pressure from 80 to 180 mm Hg.

Extrinsic Control:

• Purpose: Maintain systemic blood pressure.
• Mechanisms:
  • Hormonal pathways (renin-angiotensin-aldosterone) and neural reflexes via sympathetic nervous system.
• Operating Conditions: Mean arterial pressure far outside the normal range (

Clinical Snapshot: Anuria

• Definition: Abnormally low urinary output, defined as less than 50 ml/day.
• Implications: Can suggest that glomerular BP is insufficient for filtration.
• Causes: Conditions like acute nephritis, transfusion reactions, or crush injuries affecting nephron function.

Big Picture: From Blood Filtrate to Urine

• Filtrate Pathway:
  • Filtrate progresses through the nephron in the following order:
  1. Proximal Tubule
  2. Loop of Henle (both descending and ascending segments)
  3. Distal Tubule
  4. Collecting Duct
  • Final Passage: Collecting duct, which receives filtrate from many nephrons, then leads to the renal pelvis draining into the ureter.