Glomerular filtration

The first step in the formation of urine is glomerular filtration. The barrier to filtration is designed to facilitate the movement of fluid from the glomerular capillaries into Bowman's capsule without any loss of cellular elements or plasma proteins. Maximizing GFR has two advantages:

• Waste products are rapidly removed from the body.

• All body fluids are filtered and processed by the kidneys several times per day, resulting in precise regulation of volume and composition of these fluids.

Filtration barrier. The filtration barrier is composed of three structures:

• Glomerular capillary wall

• Basement membrane

• Inner wall of Bowman's capsule

Like the walls of other capillaries, the glomerular capillary wall consists of a single layer of endothelial cells. However, these cells are specialized in that they are fenestrated. The presence of large pores in these capillaries makes them 100 times more permeable than the typical capillary. These pores are too small, however, to permit the passage of blood cells through them.

The basement membrane is an acellular meshwork consisting of collagen and glycoproteins. The collagen provides structural support and the negatively charged glycoproteins prevent the filtration of plasma proteins into Bowman's capsule.

The inner wall of Bowman's capsule consists of specialized epithelial cells referred to as podocytes. This layer of epithelial cells is not continuous; instead, the podocytes have foot-like processes that project outward. The processes of one podocyte interdigitate with the processes of an adjacent podocyte, forming narrow filtration slits. These slits provide an ample route for the filtration of fluid.

In summary, the filtrate moves through the pores of the capillary endothelium, the basement membrane, and, finally, the filtration slits between the podocytes. This route of filtration is completely acellular.

Determinants of filtration. The glomerular filtration rate is influenced by two factors:

• Filtration coefficient

• Net filtration pressure

The filtration coefficient is determined by the surface area and permeability of the filtration barrier. An increase in the filtration coefficient leads to an increase in GFR; if the filtration coefficient decreases, then GFR decreases. However, this factor does not play a role in the daily regulation of GFR because its value is relatively constant under normal physiological conditions. On the other hand, chronic, uncontrolled hypertension and diabetes mellitus lead to gradual thickening of the basement membrane and therefore to a decrease in the filtration coefficient and GFR, and impaired renal function.

The net filtration pressure is determined by the following forces (see Figure 19.3):

• Glomerular capillary blood pressure

• Plasma colloid osmotic pressure

• Bowman's capsule pressure

Glomerular capillary pressure (PGC) is a hydrostatic pressure that pushes blood out of the capillary. The blood pressure in these capillaries is markedly different from that of typical capillaries. In capillaries elsewhere in the body, blood pressure at the arteriolar end is about 30 mmHg and at the venular end is about 10 mmHg (see Chapter 15). These pressures lead to the net filtration of fluid at the inflow end of the capillary and net reabsorption of fluid at the outflow end.

In contrast, blood pressure in the glomerular capillaries is significantly higher and essentially nondecremental. At the inflow end of the capillary near the afferent arteriole, PGC is about 60 mmHg and at the outflow end near the efferent arteriole, it is about 58 mmHg. Interestingly, the diameter of the afferent arteriole is larger than that of the efferent arteriole; therefore, the vascular resistance in the afferent arteriole is comparatively low and blood flows readily into the glomerular capillaries resulting in higher pressure. Furthermore, the smaller diameter of the efferent arteriole results in an increase in vascular resistance, which limits the flow of blood through this vessel. Consequently, the blood dams up in the glomerular capillaries, resulting in a sustained, elevated hydrostatic pressure that promotes the net filtration of fluid along the entire length of the glomerular capillaries.

Plasma colloid osmotic pressure pGC) is generated by the plasma proteins. These proteins exert an osmotic force on the fluid, which opposes filtration

Glomerular capillary

Glomerular capillary

Figure 19.3 Forces determining net filtration pressure. Three forces contribute to net filtration pressure in the glomerulus. Glomerular capillary blood pressure (P GC) is higher than that of a typical capillary (60 vs. 30 mmHg). Furthermore, P GC remains high throughout the length of the capillary because of the comparatively small diameter of the efferent arteriole, which causes the blood to dam up within the glomerular capillaries. Glomerular capillary pressure promotes filtration along the entire length of the glomerular capillaries. Plasma colloid osmotic pressure (pGC) generated by the plasma proteins opposes filtration. This force increases from 28 mmHg at the inflow end of the glomerular capillary to 35 mmHg at the outflow end, due to the concentration of plasma proteins as filtration of plasma fluid progresses. Bowman's capsule pressure (P BC) is generated by the presence of filtered fluid within Bowman's capsule. This pressure opposes filtration with a force of 15 mmHg.

Figure 19.3 Forces determining net filtration pressure. Three forces contribute to net filtration pressure in the glomerulus. Glomerular capillary blood pressure (P GC) is higher than that of a typical capillary (60 vs. 30 mmHg). Furthermore, P GC remains high throughout the length of the capillary because of the comparatively small diameter of the efferent arteriole, which causes the blood to dam up within the glomerular capillaries. Glomerular capillary pressure promotes filtration along the entire length of the glomerular capillaries. Plasma colloid osmotic pressure (pGC) generated by the plasma proteins opposes filtration. This force increases from 28 mmHg at the inflow end of the glomerular capillary to 35 mmHg at the outflow end, due to the concentration of plasma proteins as filtration of plasma fluid progresses. Bowman's capsule pressure (P BC) is generated by the presence of filtered fluid within Bowman's capsule. This pressure opposes filtration with a force of 15 mmHg.

and draws the fluid into the capillary. The pGC is approximately 28 mmHg at the inflow end of the glomerular capillaries. Because 20% of the fluid within the capillaries is filtered into Bowman's capsule, the plasma proteins become increasingly concentrated. Therefore, at the outflow end of the glom-erular capillaries, pGC is approximately 35 mmHg.

Bowmans capsule pressure (PBC) is a hydrostatic pressure generated by the presence of filtered fluid within Bowman's capsule. This pressure pushes the fluid out of the capsule and forward toward the remainder of the renal tubule for processing. Bowman's capsule pressure also tends to oppose filtration. On average, PBC is approximately 15 mmHg.

The net filtration pressure may be summarized as follows:

Net filtration pressure = PGC - pGC - PBC

Therefore, at the inflow end of the glomerular capillaries:

Net filtration pressure = 60 mmHg - 28 mmHg - 15 mmHg = 17 mmHg

At the outflow end of the glomerular capillaries:

Net filtration pressure = 58 mmHg - 35 mmHg - 15 mmHg = 8 mmHg

Under physiological conditions, values for pGC and PBC vary little. In other words, when plasma protein synthesis is normal and in the absence of any urinary obstruction that would cause urine to back up and increase PBC, the primary factor that affects glomerular filtration is PGC. An increase in PGC leads to an increase in GFR and a decrease in PGC leads to a decrease in GFR.

Glomerular capillary pressure is determined primarily by renal blood flow (RBF). As RBF increases, PGC and therefore GFR increase. On the other hand, as RBF decreases, PGC and GFR decrease. Renal blood flow is determined by mean arterial pressure (MAP) and the resistance of the afferent arteriole (aff art):

Raff art

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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