Canonical Question
Glomerulus & Tubule
Master answer
GFR
GFR:
- “The amount of glomerular ultrafiltrate formed divided by the time of filtration”
- Normal value is approx 125 mL/min or 180 L/day
- Renal blood flow 1.25l/min in 70kg male → Filtration fraction 0.2
Functional anatomy:
3 Distinct Layers:
- glomerular capillary endothelium
- highly specialised endothelium with fenestrations to ↓ filter thickness
- prevents cellular components of blood from coming into contact with BM
- glomerular BM
- made of CT; -vely charged
- acts as filter
- bowmans epithelial cells (podocytes)
- epithelial cells with foot processes → large SA
- negatively charged
- maintain BM + phagocytic functions
Direct GFR Determinants
The GFR (Net flux across the membrane) is the balance of hydrostatic pressure and oncotic pressure, as defined by the Classic Starling Equation.
\[ GFR \; = \; K_f \; \times \; NFP \]
\[NFP ={ [(P_{GC} – P_T) – \sigma \; (\pi_{GC} – \pi_T)]}\]
where
Kf = Filtration coefficient
P = hydrostatic pressure
π = oncotic pressure
σ = Staverman’s reflection coefficient ie. Permeability of membrane to protein
- Normally NFP = 17mmHg
- Tubular oncotic pressure = zero throughout
- GC oncotic pressure varies from 21 to 33 mmHg as filtrate is removed.
- Thus less GFR produced at distal end of tubule.
| Afferent end of Glomerular Capillary (mmHg) | Efferent end of Glomerular Capillary (mmHg) | |
|---|---|---|
| PGC | 60 | 58 |
| PT | 15 | 15 |
| πGC | 21 | 33 |
| NFP | 24 | 10 |
| Kf | Filtration coefficient | = LpS = Hydraulic conductivity x Surface Area Glomerular surface area = 0.8m2 • Altered by Mesangial cell contraction (see circulating factors e.g. Angiotensin II → ↓SA → ↓GFR) Patency of the normal capillary wall structure (ie in tubular dysfunction Kf ↑’s ↑GFR) |
| PGC | hydrostatic pressure in capillary | relates to • RBF which is autoregulated for MAP 70-170mmHg • relative afferent/efferent arteriolar tone Affected by • Catecholamines • Local autoregulation -> Myogenic -> Tubuloglomerular feedback -> Hormones (see below) |
| PT | hydrostatic pressure in tubule | relates to • obstruction to urinary flow (usually pathological) • ↑PT → ↓ GFR (ie post renal obstructiion causing renal failure) |
| πGC | oncotic pressure in capillary | relates to • plasma protein concentration (incr in dehydration, decreased in heart failure) • ↑Systemic plasma oncotic pressure → ↑πGC → ↓GFR • ↓Renal plasma flow → ↑πGC → ↓GFR |
| πT | oncotic pressure in tubule | • usually zero, but can increase in renal failure/proteinuria • ↑’d πT → ↑GFR |
| σ | Staverman’s reflection coefficient | • Permeability of membrane to protein usually 1 (no protein leak) • can decrease with nephritis/proteinuria |
Factors influencing GFR
Circulating Factors
- Prostaglandins
- PGI2 and PGE2 → vasodilates → ↑ renal blood flow → ↑ GFR
- ↓ PGE2, PGI2 and NO levels → inhibits afferent arteriolar vasodilation → ↓ GFR
- Long term → ↓ renin release → ↓ ATII-induced efferent arteriolar vasoconstriction → ↓ GFR
- Noradrenaline / Adrenaline
- constrict renal afferent and efferent arterioles → ↓ renal blood flow and reducing filtration → ↓GFR
- Constrict mesangial cells to → ↓ GFR.
- Mesangial cell tone:
- Angiotensin 2, Endothelin, vasopressin → ↓ glomerular surface area and GFR
- ANP, PGE2, Dopamine and cAMP → all increase GFR
Solute factors
- Size
- < 7 kDa (Eg. glucose, ions, urea, H2O) filtered freely,
- > 70 kDa (Eg. albumin) are not filtered;
- neutral particles < 4 mm diameter filtered freely, > 8 mm are excluded
- Charge
- Negatively charge (Anionic) particles repulsed
- Cationic substances filtered more readily
- Protein binding
- Albumin excluded
Disease Factors
- Filtration decreases
- Shock → decreased glomerular pressure
- Obstruction → increased bowman’s capsule hydrostatic pressure
- Hypoproteinaemia → hepatic failure, nephrotic syndrome
JC / Gladwin / Sakurai / Kerr 2020
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2009A Q13 | Outline the factors that determine the composition and volume of glomerular filtrate in a normal person. | historical_member | — |
| 2014A Q23 | What is the Glomerular Filtration Rate (GFR)? Discuss the physiological factors that can influence it. | historical_member | — |
| 2016A Q04 | Discuss the factors that influence filtration across the glomerular basement membrane. | historical_member | — |