H1iii / 17B03: Factors determing filtration of a substance at renal glomerulus

17B03: Exam Report

Describe the factors that determine the filtered load of a substance at the renal glomerulus.

67% of candidates passed this question.

A good place to start was with the correct equation for a filtered load and a description of the components. Better answers described the components and how they differ and change over the glomerulus. Many candidates usefully based answers around the Starling forces.

A summary of factors including the role of plasma concentration, protein binding, molecular size and charge was required to pass. Many answers gave examples for the effects of size and charge and relate endocrine responses to specific alterations in arteriolar tone and how this affected filtration. A detailed discussion of cardiovascular and endocrine responses to hypovolaemia was not required.

Some candidates confused clearance with filtered load. Candidates are reminded to write legibly – especially where subscripts and Greek letters are used. Directional arrows (if used) should correlate with text.

H1iii / 17B03: Describe the factors that determine the filtered load of a substance at the renal glomerulus

Filtered Load of ‘x’ = GFR x {Plasma [x]}

  • Filtered load of a substance depends on
    • GFR
    • Concentration of the substance in plasma
    • Permeability of ‘x’

 

GFR

Renal blood flow = 1.2L/min

45% = HCt, ∴55% = plasma

∴RENAL PLASMA FLOW = 0.55 x 1.1L/min = 600mL/min

of the 600mL entering glomeruli:

  • 125mL/min goes into Bowman’s space (GFR)
  • 475mL/min goes to Eff. Arterioles → peritubular caps

Normal GFR = 125ml/min

RATE OF FILTRATION = PERMEABILITY x SA x NFP

 SURFACE AREA

  • Depends on no. of functioning nephrons
  • This ↓with ↑age
  • NET FILTRATION PRESSURE

NFP = (PGC – πGC) – (PBC – πBC)

  • NFP is the sum of hydrostatic + oncotic pressures resulting from protein
  • On either side of the capillary wall are 4 pressures → 2 HYDROSTATIC & 2 ONCOTIC
  • KA STARLING’S FORCES

PGLOM CAP

  • Hydrostatic P of caps is high
  • Minimal ↓along length of caps because large cross sectional area of glomeruli results in v. small resistance to flow
  • HYDROSTATIC P of GC is determined by Arterial P & resistance of Aff. & Eff. Arterioles
  • ∆ arterial P will ∆ PGC in same direction, but because of autoregulation this effect is minimal
  • ↑ resistance = ↓PGC = ↓GFR
  • ↑ Resistance = ↑PGC = ↑GFR

ΠGLOM CAP

  • Entering capillaries πGC = πplasma
  • ΠGC ↑along length of caps because large amounts of protein free fluid are being filtered out
  • ↑πGC = ↓NFP

PBC

  • Tubules constantly carry fluid away from Bowman’s capsule
  • ∴PBC is v. low & often negligible/excluded from NFP equation
  • Only of importance in pathology → i.e. obstruction to tubule outflow → ↑PBC → ↓NFP

ΠBC

  • Should be zero
  • Any protein in BC will ↑filtration

Mean NFP = 17mmHg

↓

Which produces the 180L/day of glomerular filtrate

  •  Rise in GFR = increase filtration load ‘x’

Plasma Concentration [x]

Normal GFR = 125ml/min

Substance ‘x’ must be in the plasma to be filtered at the glomerulus

Higher the [x] in plasma the more that will be presented for filtration (at constant GFR)

Substance ‘x’ Characteristics Amenable to Filtration (PERMEABILITY)

Filtration barrier of Renal Corpuscle is formed by 3 layers:

  1. CAPILLARY ENDOTHELIUM
  2. BM
  3. BOWMAN’S CAPSULE EPITHLIUM

1) Cap Endothelium

  • Fenestrated
  • Freely permeable H2O, small solutes <7000Da
  • Impermeable to cells (RBC, WBC, platelets)
  • Has negatively charged glycoproteins ∴limits filtration of large anionic proteins

2) Basement Membrane

  • Covers endothelial cells
  • Negatively charged proteins
  • Main role is to filter based on charge; repels negative charge ie Albumin

3) Bowman’s Capsule Epithelium

  • Covered by PODOCYTES
  • FILTRATION SLIT DIAPHRAGMS
  • Size selective filtration
  • Stops proteins & macromolecules passing into Bowman’s space (i.e. albumin is 70,000Da ∴should not appear in glomerular filtrate)

∴ amino acids, electrolytes, glucose are filtered in same [  ] as plasma

Glomerular filtrate should NOT contain cells & large molecular weight proteins