Physiology for MRCEM Primary

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Renal physiology

Mechanism of filtration

[box type=”download”] Mechanism of filtration in health. Glomerular filtration  Normal GFR and filtration fraction in adults  The three glomerular filtration barriers and the importance of molecular size  Factors affecting GFR (Starling forces, relative arteriolar resistance)  The role of vasoactive substances in affecting GFR [/box]

Glomerular capillaries are surrounded by Bowman’s capsule, the inner surface of which and the capillaries are covered by specialized epithelial cells (podocytes).
The glomerulus is interspersed with mesangial cells which are phagocytic and contractile; contraction may limit the filtration area and alter filtration.
Mesangial cells are also found between the capsule and macula densa (extraglomerular mesangial cells).

Glomerular ultra-filtration

The glomerular filtration rate (GFR) is ∼125 mL/min in humans.
The renal plasma flow is ∼600 mL/min, so the filtration fraction is ∼20%.
Fluid and solutes have to pass three filtration barriers:
1. The glomerular capillary endothelium, – fenestrated with small (70 nm) pores.
2. A specialized capillary basement membrane containing negatively charged glycoproteins, which is thought to be the main site of ultrafiltration.
3. Modified epithelial cells (podocytes) with long extensions (primary processes) that engulf the capillaries and have numerous foot-like processes (pedicels) directly contacting the basement membrane. The regular gaps between pedicles are called filtration slits, and restrict large molecules.
Podocytes maintain the basement membrane and, like mesangial cells, may be phagocytic and partially contractile.

Substances with molecular weights of <7000 Da pass freely, but larger molecules are increasingly restricted up to 70 000 Da, above which filtration is insignificant.
Negatively charged molecules are further restricted as they are repelled by negative charges in the basement membrane.
Thus, albumin (∼69 000 Da), which is also negatively charged, is filtered in minute quantities, whereas small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance.
This means that the glomerular filtrate is almost protein free, but otherwise has an identical composition to plasma.

Factors determining the glomerular filtration rate

GFR is dependent on the difference between the hydrostatic and oncotic pressures in the glomerular capillaries and Bowman’s capsule, as determined by Starling’s equation.
The glomerular capillary pressure (Pc) is greater than that elsewhere (∼45 mmHg) because of low afferent but high efferent resistances.
Pressure in Bowman’s capsule (PB) is ∼10 mmHg, the net hydrostatic force driving filtration is (Pc – PB) or ∼35 mmHg.
This is opposed by the oncotic pressure of capillary plasma (πc; ∼25 mmHg); the filtrate oncotic pressure is essentially zero (no protein).
Thus, GFR ∝ (Pc –PB) – πc.
It should be noted that, because the filtration fraction is appreciable (∼20%) and proteins are not filtered, the plasma protein concentration and thus πc will rise as blood traverses the glomerulus.
In peritubular capillaries, where the hydrostatic pressure is very low, this increase in πc promotes reabsorption.
GFR is therefore strongly dependent on the relative resistance of afferent and efferent arterioles, which is
influenced by sympathetic tone and other vasoactive agents.
GFR is constant over a wide range of blood pressure (90–200 mmHg) because of the autoregulation.
Renal disease, circulating and local vasoconstrictors, and sympathetic activation all reduce GFR, although angiotensin II preferentially constricts efferent arterioles, and thus increases GFR, or maintains GFR if BP falls.