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Renal Tubular Physiology — Filtered Load

Current · V5 (2025) → E1.iv Historical · V4 (2023) → H1.iii 1 exam appearance

2017B Q03

Exam question

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

CICMWrecks answer

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
K_f = Filtration coefficient
P = hydrostatic pressure
π = oncotic pressure
σ = Staverman’s reflection coefficient ie. Permeability of membrane to protein

K_f	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)
P_GC	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)
P_T	hydrostatic pressure in tubule	relates to • obstruction to urinary flow (usually pathological) • ↑P_T → ↓ GFR (ie post renal obstructiion causing renal failure)
π_GC	oncotic pressure in capillary	relates to • plasma protein concentration (incr in dehydration, decreased in heart failure) • ↑Systemic plasma oncotic pressure → ↑π_GC → ↓GFR • ↓Renal plasma flow → ↑π_GC → ↓GFR
π_T	oncotic pressure in tubule	• usually zero, but can increase in renal failure/proteinuria • ↑’d π_T → ↑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

Reusable content

Formulae used in this answer

Direct GFR Determinants

CWF-0110

GFR \; = \; K_f \; \times \; NFP

Direct GFR Determinants

CWF-0111

NFP ={ [(P_{GC} - P_T) - \sigma \; (\pi_{GC} - \pi_T)]}

Filtered Load

CWF-0112

Filtered \; Load \; = \; GFR \; \times \; plasma \; concentration \; of \; substance \; (Px)

Answer by Gladwin, JC, Kerr, Sakurai

Past papers

Exam appearances

1 appearance

Exam	Exact exam wording	Candidate success
2017B Q03	Describe the factors that determine the filtered load of a substance at the renal glomerulus	67%