Starlings Forces

The extent to which fluid moves along, into and out of a capillary depends on the balance of 'Starling's forces'. The major force pushing fluid along and out of the capillary is blood hydrostatic pressure. The major force driving fluid back into a capillary is the osmotic pressure of the blood. In brief, if blood hydrostatic presure is greater than blood osmotic pressure then fluid moves out of the capillary. If blood Osmotic pressure is greater than blood hydrostatic pressure, then fluid moves into the capillary. Over the length of a 'typical' capillary, blood hydrostatic pressure falls so that the balance shifts from a driving force for efflux to a driving force for influx. Read on for more details and to understand why the glomerular capillaries in Bowman's capsule are slightly different.

In any capillary....

In glomerular capillaries:

The main driving force for filtration is the hydrostatic pressure of the blood. The Starlings forces in renal glomerular capillaries are slightly different from those elsewhere in the body. Hydrostatic pressure remains high along the whole length of the capillary and so the balance of the Starling forces is always towards fluid efflux from the capillary. It would be pointless to filter the blood at the arterial end of the capillary if most of the filtrate came back with a fall in hydrostatic pressure before it reached the far end. The main reason that the hydrostatic pressure stays high in the glomerular capillaries is that they don't coalesce into a vein but rather into an arteriole. The efferent arterioles are high-pressure vessels with muscular walls just like the afferent arterioles.

The other Starling forces are also slightly different in glomerular capillaries. In a 'normal' capillary, interstitial fluid osmotic pressure is a significant factor but, as the glomerular filtrate is practically protein free, the equivalent term Bowman's capsule osmotic pressure is negligible. Again, in a 'normal' capillary interstitial hydrostatic pressure is zero whereas the hydrostatic pressure in Bowman's capsule is about 10mM of mercury.

Filtration

The filter itself is composed of three layers, the capillary wall (fenestrated capillaries composed of endothelial cells), the basement membrane (connective tissue) and the nephron wall (epithelial cells). Solutes have to pass all three layers in order to leave the blood and enter the urine. The capillary walls are sufficient to keep blood cells in their place. So far as anything smaller is concerned, the major barrier to filtration is the basement membrane. This is laid down by specialised epithelial cells, part of the nephron, called podocytes. In between the glomerular capillaries there are also mesangial cells, as these are contractile, they may have a role in regulating the surface area for filtration. These cells are also phagocytic and so may be involved in mopping up molecules that get stuck in the filter. The overall effect of the filter is to completely pass anything less than 4nm in diameter, roughly anything with a molecular weight less than 7000 and to (almost) completely exclude anything with a diameter greater than 8nm or with a molecular weight greater than 70,000. As you move in size between the lower and upper limit you will get less and less of the substance passing through the filter.

The charge of molecule is also important in determining how easily it passes through the filter. The basement membrane and possibly the 'slit pores' (gaps or spaces) between the podocytes contain fixed negative charges. These will act to repel negatively charged molecules. Albumin is a protein that falls just under the upper limit for filtration, but because of its negative charge, practically no albumin gets through into the urine. Uncharged dextran molecules of a similar size are about 20 times more permeable than abumin and so would show up in the urine (if dextran was normally found in the plasma that is, which it isn't.)

The rate at which fluid passes through the filter is called the glomerular filtration rate (GFR). In order for the nephron and indeed the kidney as a whole to function efficiently, it is important that the GFR is kept constant. Autoregulation of glomerular capillary blood flow is one of the mechanisms by which this is accomplished. Another is by regulating the glomerular ultrafiltration coefficient (Kf). The Kf is essentially a measure of how hard it is for substances to cross from the blood to the urine, in other words it is a measure of the resistance of the filter. Kf is the product of the hydraulic conductivity of the filter and the filter surface area.

GFR = K_f (BHP + BCOP - BCHP - BOP)

GFR is also dependent on blood flow because BHP and to a certain extent BOP are affected by the rate of blood flow through the capillaries.

Not all the fluid in the blood passing through the glomerular capillaries can be filtered through into the urine. If it were, the efferent arterioles would contain a nasty sludge of blood cells and plasma proteins. Obviously, the blood must retain sufficient fluid to be liquid and to keep moving through the blood vessels. Usually about 20% of the plasma passes through the filter into the urine. This is referred to as the filtration fraction.

As usual my diagrams give very little indication of anatomy. Here is an electron micrograph that shows what the filter in Bowman's capsule really looks like.