Canonical Question
Glomerulus & Tubule
Master answer
Filtered Load
- It is the amount of substance that is filtered per unit time.
- For freely filtered substances, The filtered load is equal to:
\[Filtered \; Load \; = \; GFR \; \times \; plasma \; concentration \; of \; substance \; (Px) \]
- E.g: Na: Filtered load = GFR x Px = 125ml/min x 0.14mEq/ml(or 140mEq/L) = 17.5 mEq/min.
- The filtered load is what is presented to the rest of the nephron to handle.
- For substances that are freely filtered:
- The filtered load varies only with plasma concentration and GFR.
- A rise in GFR, at constant plasma concentration increases the filtered load, as does a rise in plasma concentration at constant GFR.
- For substances which are not freely filtered, filtration also depends on
- protein binding
- molecular size
- charge
GFR
Direct 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
| 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 |
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
Disease Factors
- Filtration decreases
- Shock → decreased glomerular pressure
- Obstruction → increased bowman’s capsule hydrostatic pressure
- Hypoproteinaemia → hepatic failure, nephrotic syndrome
Plasma Concentration
Plasma concentration is a complex interplay of factors:
- Extrinsic substances like drugs: dosage, time and route of administration, the bioavailability of the drug
- Absorption / Production of substance
- Distribution
- Metabolism
- Excretion
- Inter-relationships with other substances or drugs
- Concurrent drug administration may profoundly affect plasma drug concentrations
Additional Factors for Substances not Freely filtered
- Molecular 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
- Molecular Charge
- Negatively charge (Anionic) particles repulsed
- Cationic substances filtered more readily
- Protein binding
- Albumin excluded
JC / Gladwin / Sakurai / Kerr 2020
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2017B Q03 | Describe the factors that determine the filtered load of a substance at the renal glomerulus | historical_member | — |