52 Urinary Homeostasis

Regulation of Glomerular Filtration

In a healthy body, GFR remains relatively constant even in the face of substantial changes in arterial blood pressure. By adjusting resistance to the flow of blood, renal autoregulation prevents significant fluctuations in GFR when systemic arterial blood pressure rises or falls. Two mechanisms are involved in this intrinsic control. The myogenic mechanism results from the inherent tendency of vascular smooth muscle to contract when stretched. This means that the diameter of afferent arterioles changes in response to fluctuations in blood pressure. Increasing blood pressure in the afferent arteriole stretches the smooth muscle in the wall of the arteriole. As a result, the smooth muscle will contract and the arteriole will vasoconstrict. This reduces the diameter of afferent arterioles, and blood flow. Decreasing blood pressure in the afferent arteriole removes the stretch of the smooth muscle in the wall of the arteriole. As a result, the smooth muscle will relax and the arteriole will vasodilate. This increases the diameter of afferent arterioles and blood flow. In both cases, the result is a relatively stable GFR.

The second element of renal autoregulation is the tubuloglomerular feedback mechanism The macular densa cells of the distal convoluted tubule are part of the juxtaglomerular apparatus and are responsible for the tubuloglomerular feedback mechanism. The macula densa cells respond to the sodium concentration in the filtrate that flows from the ascending limb of nephron loop into the distal convoluted tubule. The sodium concentration in the filtrate is directly related to the rateglomerular filtration rate (GFR). When GFR is high, there is not enough time for reabsorption, and the filtrate will have a high sodium concentration. The macular densa cells respond to this high sodium concentration by releasing the vasoconstrictor adenosine, which narrows the diameter of the afferent arterioles. Reduced blood flow lowers the net filtration pressure and the GFR, which enhances sodium chloride reabsorption. Conversely, when GFR is low the filtrate will have a low sodium concentration. The release of the paracrine agent by macula densa cells is inhibited. As a result, the afferent arterioles dilate and increase tje blood flow into the glomerulus. The result is to increase net filtration pressure in the glomerulus and increase GFR. This has the opposite effect of macula densa cell activation: it increases the amount of filtered sodium, and it reduces sodium reabsorption.

These two autoregulatory mechanisms help keep the flow of blood through the kidneys relatively constant when mean systemic arterial blood pressure is within a range of approximately 80 mm Hg to 180 mm Hg. However, autoregulation cannot adjust for changes in systemic blood pressure that are outside of this range.

Neural Regulation

The sympathetic nerve fibers that innervate renal blood vessels provide an extrinsic regulatory mechanism for GFR. During extreme stress or blood loss, the sympathetic nervous system must meet the needs of the body as a whole, for example, by temporarily reducing kidney activity and redirecting blood to other vital organs. In such situations, neural controls override renal autoregulation. The sympathetic nerve fibers release the neurotransmitter norepinephrine. Norepinephrine activates alpha-adrenergic receptors on vascular smooth muscle and causes afferent arterioles to constrict. The resulting reduced blood flow into glomerular capillaries lowers net filtration pressure and GFR. This decreased renal blood flow helps maintain blood volume by reducing urine output and increasing perfusion to other body tissues.