Describe the factors which help maintain the constancy of the glomerular filtration rate (GFR) despite fluctuations in systemic arterial blood pressure.

Outline:

·        Definition of GFR

·        Importance of maintaining constant GFR

·        Autoregulatory responses:

- Myogenic

- Tubuloglomerular feedback

·        Reflex control:

- Neural

- Hormonal

Essay:

            The glomerular filtration rate (GFR) is determined by the sum of the hydrostatic and colloid osmotic forces across the glomerular membrane, which gives the net filtration pressure and K, the glomerular ultrafiltration coefficient.

            The GFR in an average-sized normal man is about 125 mL/min. The kidneys maintain a high GFR which allows it to rapidly remove waste products from the body that depend primarily on glomerular filtration for their excretion. A second advantage of a high GFR is that it allows all the body fluids to be filtered and processed by the kidney many times each day. This high GFR allows the kidneys to precisely and rapidly control the volume and composition of the body fluids.

            For most substances, the rates of filtration and reabsorption are extremely large relative to the rates of excretion. Therefore, subtle adjustments of filtration or reabsorption can lead to relatively large changes in renal excretion. Besides fluctuations in arterial pressure, the other factors that affect GFR are changes in renal blood flow, glomerular capillary permeability, glomerular capillary hydrostatic pressure and afferent or efferent arteriolar constriction.

            Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow and GFR relatively constant, despite marked changes in arterial blood pressure. The major function of autoregulation in the kidneys is to maintain a relatively constant GFR and to allow precise control of renal excretion of water and solutes.

            The autoregulatory responses are tubuloglomerular feedback and myogenic responses. The tubuloglomerular feedback mechanism links changes in NaCI concentration at the macula densa with the control of renal arteriolar resistance. This feedback helps to ensure a relatively constant delivery of NaCI to the distal tubule and helps to prevent spurious fluctuations in renal excretion that would otherwise occur. This feedback mechanism is effected through the juxtaglomerular complex, which consists of macula densa cells in the initial portion of the distal tubule and juxtaglomerular cells in the walls of the afferent and efferent arterioles. A decreased GFR slows the flow rate in the loop of Henle, causing an increase in reabsorption of sodium and chloride ions in the ascending loop of Henle and thereby reducing the concentration of NaCI at the macula densa cells. This initiates a signal from the macula densa which decreases the resistance of the afferent arterioles, raising glomerular hydrostatic pressure and returning GFR to normal, and increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles. Renin catalyzes the formation of angiotensin I which is converted to angiotensin II. Angiotensin II constricts the efferent arterioles, thereby increasing glomerular hydrostatic pressure and return GFR to normal. When both of these mechanisms are functioning together, the GFR changes only a few percentage points even with large fluctuations in arterial pressure.

            A second mechanism that maintains GFR is the myogenic mechanism. Stretch of vascular wall due to increased renal blood flow (which increases GFR) opens calcium ions. The increased movement of calcium ions from the extracellular fluid into the cells causes them to contract. This contraction serves to prevent overdistention of the vessel and at the same time, by raising vascular resistance, helps to prevent excessive increases in renal blood flow and GFR when arterial pressure increases.

            The reflex control mechanisms are employed only when homeostasis is threatened. The afferent and efferent arterioles are innervated by sympathetic neurons. Norepinephrine is released by sympathetic nerves, and circulating epinephrine is secreted by the adrenal medulla. They bind on the alpha receptors on the afferent arterioles, causing vasoconstriction, decreasing GFR. At low levels of angiotensin, constriction of the efferent arteriole predominates. However, when blood pressure drops too low, angiotensin II levels increase and this causes vasoconstriction of both the afferent and efferent arterioles, decreasing GFR. Nitric oxide (NO), an endothelium-derived relaxing factor, plays an important vasodilatory role in normal conditions, and counteracts vasoconstriction produced by angiotensin II and catecholamines. An increase in shear force acting on endothelial cells in the arterioles, as well as a number of hormones, increase the production of NO. This increased NO production causes vasodilation of the afferent and efferent arterioles in the kidneys. Other substances such as prostaglandins and endothelin do not normally play a role in the regulation of GFR in healthy, resting people. They become significant only during pathophysiological conditions such as hemorrhage.