Renal Physiology: Glomerular Filtration

Glomerular Filtration

• The bulk flow of fluid from the glomerular capillaries into Bowman's capsule
• The filtrate contains most inorganic ions and low-molecular-weight organic solutes
• The glomerular filtration rate (GFR) is the volume of filtrate formed per unit time
• In a normal young adult male, the GFR is an incredible 180 L/day (125 mL/min)
• Urine formation results from glomerular filtration, tubular reabsorption, and tubular secretion
• Urinary excretion rate = Filtration rate - Reabsorption rate + Secretion rate

Renal Handling of Substances

• Some substances are freely filtered, but neither reabsorbed nor secreted, therefore excretion rate = filtration rate
• Some substances are freely filtered, but partly reabsorbed, therefore urinary excretion rate is less than filtration rate
• Some substances are freely filtered and totally reabsorbed, resulting in a zero urinary excretion rate
• Some substances are freely filtered and not reabsorbed, but are secreted, therefore excretion rate = filtration rate + tubular secretion rate

Structure of Glomerular Capillary Membrane

• The glomerular capillary membrane has three major layers:
  • Endothelial cells: Perforated by large fenestrae ("windows") and rich in fixed negative charges
  • Basement membrane: About 50nm thick, contains glycoproteins and proteoglycans, and has a net negative charge.
    • In minimal change nephropathy, the negative charges are lost leading to proteinuria or albuminuria
  • Epithelial cells: Contain podocytes with pedicels which interdigitate forming slits through which the filtrate enters Bowman's space. Podocyte membranes also have a high density of negative charge
• The glomerulus also contains mesangial cells, which act as phagocytes and can contract

Factors Affecting Filtration

• The glomerular capillary membrane is thicker than most other capillaries, but more porous
• Filtration rate of any substance depends on:
  • Molecular size: Freely passes neutral substances up to 4nm, but almost completely excludes those greater than 8nm
  • Electrical charge: Negatively charged molecules are impeded by electrostatic repulsion; positively charged molecules are favored
• Filtration fraction (FF): The fraction of the renal plasma flow that is filtered, averaging about 0.2

Determinants of GFR

• The pressures driving fluid movement across the glomerular capillary wall are the Starling forces:
  • Glomerular hydrostatic pressure (PG): Pressure within the glomerular capillary
  • Bowman's capsule hydrostatic pressure (PB): Pressure within Bowman's capsule
  • Glomerular capillary colloid osmotic pressure (πG): Pressure due to proteins in the glomerular capillary
  • Bowman's capsule colloid osmotic pressure (πB): Pressure due to proteins in Bowman's space
• GFR = Kf x net ultrafiltration pressure
• Net filtration pressure = Forces Favoring Filtration - Forces Opposing Filtration
  • Forces Favoring Filtration: PG (60 mmHg) and πB (0 mmHg)
  • Forces Opposing Filtration: PB (18 mmHg) and πG (32 mmHg)
• Net filtration pressure = [(60 + 0) - (18 + 32)] = 10 mmHg

Filtration Coefficient (Kf)

• Kf is the water permeability of the glomerular capillary wall
• Kf is calculated from GFR and net filtration pressure
• Normal Kf is about 12.5 ml/min/mm Hg
• Kf of renal capillary glomeruli is 400 times higher than other capillary systems

Factors Decreasing GFR

• Decreased Kf
  • Uncontrolled hypertension
  • Diabetes mellitus (thickening of glomerular basement membrane)
• Increased Bowman's capsule hydrostatic pressure
  • Obstruction of urine flow (e.g., ureteral stone)
• Increased glomerular capillary colloid osmotic pressure
• Constriction of the afferent arteriole

Factors Increasing GFR

• Increased glomerular capillary hydrostatic pressure
  • Increased arterial pressure
  • Increased efferent arteriolar resistance
• Increased sympathetic nerve activity
  • Vasoconstriction of afferent and efferent arterioles
  • Reduced renal blood flow
• Prostaglandins (e.g., PGE2, PGI2)
  • Vasodilation of afferent and efferent arterioles
• Dopamine (low doses)
  • Vasodilation of cerebral, cardiac, splanchnic and renal arterioles
• Nitric oxide (NO)
  • Vasodilation of afferent and efferent arterioles
  • Released by endothelial cells in response to increased shear stress or pressure
• Endothelin
  • Potent vasoconstrictor of endothelial origin
  • Implicated in the nephrotoxicity of some drugs (e.g., cyclosporine)

Explore the processes of glomerular filtration and renal handling of substances in this quiz. Understand concepts like the glomerular filtration rate (GFR) and how various substances are filtered and reabsorbed by the kidneys. Test your knowledge on urine formation and the dynamics of substance handling in renal physiology.