Question

Explain glomerular filtration and the mechanisms that control its pressure and rate. Why is GFR critical to normal urine formation?

Answer 1

Glomerular filtration rate (GFR) is the rate of flow of blood and its filtration through the kidneys. Blood flows into Bowman’s capsule from where it enters the glomerular filtration apparatus via afferent arterioles. Bowman’s capsule covers the glomerulus and has visceral and parietal epithelial layers. Visceral layer is made up of podocytes that allow fluid to enter the nephron via small slits. This layer is present above the basement membrane. Large molecules cannot pass through the visceral layers. Non-filterable larger molecules such as RBCs, albumin leaves the kidneys via efferent arterioles.

25% of the cardiac output enters the glomerulus, which has a fenestrated epithelium. fenestrated epithelium allows the movement of molecules less than 70nM size to pass through. Negatively sized cations in the epithelium will allow cations to be filtered. The visceral later has the foot processes of podocytes that allow molecules of 14nM to pass through.

Oncotic pressure in Bowman’s capsule will allow filtration into renal tubules. This oncotic pressure is aided by hydrostatic pressure in the capillaries. On the other hand, Hydrostatic pressure in Bowman’s capsule and oncotic pressure in capillaries oppose glomerular filtration.

GFR is regulated in various mechanisms:

a. Mean arterial pressure does not normally alter the renal blood plasma flow through the glomerulus. However when the hydrostatic pressure in the afferent arteriole increases due to high blood pressure, there is stretching of smooth muscles in arterioles induced. As a result, inward directed ion channels get activated, inducing depolarization and muscle contraction, and vasoconstriction.. The renal blood flow is therefore adjusted and will not affect the kidneys. Smooth muscle dilation will occur when there is decreased blood pressure to maintain renal blood flow through the kidneys.

b. RAAS (renin-angiotensin –aldosterone system) also maintains the GFR. Decreased stretch in afferent arterioles will cause secretion of renin by the juxtamedullary cells of the afferent arterioles. Reni activates angiotensinogen, to form angiotensin. Angiotensin I is converted by ACE (angiotensin converting enzyme) to angiotensin II, which then induces secretion of aldosterone in the adrenal glands. Aldosterone acts on renal tubules to increase sodium reabsorption and potassium excretion to maintain GFR via perseverance of renal perfusion.

c. GFR is also maintained by the Tubuloglomerulo-feedback via the macula densa. The macula densa are present in the ascending limb of distal tubules of the kidneys. The GFR increase via increased delivery of electrolytes is sensed by the macula densa. Chloride concentration increases in the intracellular compartment of macular densa, resulting in depolarization. As a result, ATP, adenosine and thromboxane which are paracrine mediators are produced, which then contract the smooth muscles. This leads to decreased renal blood flow and reduces the GFR to normal range. Macula densa also stimulates the RAAS system.

GFR is important for formation of urine. GFR maintains the filtration of blood via the kidneys. If the GFR decreases, then the amount of blood filtered by the kidneys decreases. This will decrease the amount of urine produced as less blood will flow through the kidneys. It is known that 25% of cardiac output enters the glomerulus. Fluid in urine is obtained from this cardiac output. Although, high molecular weight compounds are returned back to the blood via efferent arterioles, most of the fluid in blood passes through the glomerulus. Fluid reabsorption takes places in descending Loop of Henle via osmosis and in collecting duct via aquaporin channels. Thus, urine production will depend on the GFR as it controls the amount of fluid entering the kidneys. Hence, maintaining GFR is critical fro urine production as decrease in GFR will reduce urine production as well.