The functional units of the kidneys are numerous microscopic structures called nephrons. Nephrons contain both vascular and tubular components that together produce urine. The production of urine is tightly controlled by a number of homeostatic mechanisms that ultimately regulate blood volume and blood composition. Glomerular filtration is the first of three processes within a nephron that produce urine. Glomerular filtration occurs at a ball of capillaries called the glomerulus located between the afferent and efferent arterioles. Recall that filtration is the bulk movement of fluid out of the capillaries driven primarily by capillary hydrostatic pressure. Newly formed filtrate collects in the glomerular capsule before traveling on to other tubular components of the nephron. The glomerular filtration rate, or GFR, is the total volume of filtrate created by the kidneys each minute. GFR is affected by a number of important regulatory mechanisms. Despite the diversity of these mechanisms they all work by changing glomerular hydrostatic pressure, or HPG. Increases in HPG which tend to increase blood flow through the glomerulus, increase GFR , and decreases in HBG which tend to decrease blood flow, decrease GFR. Changes in GFR occur through two types of mechanisms. Intrinsic controls which occur strictly within the kidney, and extrinsic controls which involve components outside the kidney. Intrinsic controls, also known as renal auto regulation, work to maintain homeostasis by keeping GFR constant. In contrast, extrinsic controls work to maintain homeostasis by keeping systemic blood pressure constant. These efforts to control systemic blood pressure by neural and hormonal mechanisms indirectly affect GFR to the extent that they change HPG. There are two main types of intrinsic controls. The myogenic mechanism and the tubular glomerular feedback mechanism. Both work to keep GFR constant despite moderate changes in systemic blood pressure. The myogenic mechanism is an intrinsic response of smooth muscle within the afferent arteriole. The smooth muscle contracts when involuntarily stretched by an increase in blood pressure. This vasoconstriction causes a decrease in HBG which helps maintain a normal GFR. A decrease in systemic blood pressure produces the opposite response, dilation of the afferent arterioles which again helps maintain a normal GFR. The second intrinsic control is the tubuloglomerular feedback mechanism and involves the juxtaglomerular apparatus, or JGA, of the nephron. The JGA exists at the junction of the afferent arteriole and the most distal portion of the loop of Henle. In this way, macula densa cells within the JGA are exposed to the partially processed filtrate from their own glomerulus. Macula densa cells constantly monitor the sodium chloride concentration of this filtrate. If GFR is too high such that the filtrate is passing through the tubule too quickly, filtrate sodium chloride concentration will be high due to insufficient reabsorption. Macula densa cells respond by releasing a vasoconstricting chemical that decreases afferent arteriole diameter. As with the myogenic mechanism, vasoconstriction decreases HPG which returns GFR to a less rapid pace. The opposite occurs if GFR is already too low. That is, low GFR causes low sodium chloride levels resulting in less vasoconstriction which increases GFR. Extrinsic controls of GFR include sympathetic nervous system controls and renin angiotensin mechanism. These both serve to maintain systemic blood pressure and can override intrinsic mechanisms working to keep GFR constant. Under normal conditions, neural mechanisms controlling systemic blood pressure do not appreciably affect GFR. This is because intrinsic mechanisms keep GFR constant, despite moderate changes in blood pressure. However, under severe stress such as hypovolemic shock, the sympathetic nervous system responds with massive vasoconstricting signals in an effort to maintain systemic blood pressure. This sympathetic activity constricts afferent arterioles of the glomeruli, which decreases GFR. This decrease in GFR occurs despite opposing efforts of intrinsic mechanisms to keep GFR constant. The other type of extrinsic control is hormonal. Specifically, the renin angiotensin mechanism which serves to increase blood pressure and blood volume. Renin is an enzyme released into the blood by the granular cells of the juxtaglomerular apparatus. A variety of signals related to low blood pressure trigger renin release. The presence of renin in the blood eventually leads to the production of angiotensin II which also circulates within the blood. Angiotensin II has two main effects. First, like the sympathetic nervous system, angiotensin II is vasoconstricting which tends to decrease GFR. Second, angiotensin II causes the release of another hormone, aldosterone, which serves to increase blood volume and alleviate the current threat to blood pressure homeostasis. To review, the glomerular filtration rate is the total volume of filtrate created by the kidneys each minute. GFR is affected by a number of homeostatic mechanisms. Intrinsic control mechanisms, including myogenic stretch and tubuloglomerular feedback work to maintain constant GFR. In contrast, extrinsic control mechanisms such as those involving the sympathetic nervous system and the renin angiotensin mechanism work to maintain systemic blood pressure and exert indirect effects on GFR.