17.4: Urine Formation and Glomerular Filtration Rate (GFR)
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- 128796
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- Describe glomerular filtration rate (GFR), state the average value of GFR, and explain how clearance rate can be used to measure GFR
- List common symptoms of kidney failure
- Describe the myogenic and tubuloglomerular feedback mechanisms and explain how they affect urine volume and composition
- Describe the function of the juxtaglomerular apparatus
Having reviewed the anatomy and microanatomy of the urinary system, now is the time to focus on the physiology. You will discover that different parts of the nephron utilize specific processes to produce urine: filtration, reabsorption, and secretion. You will learn how each of these processes works and where they occur along the nephron and collecting ducts. The physiologic goal is to modify the composition of the plasma and, in doing so, produce the waste product urine.
Failure of the renal anatomy and/or physiology can lead suddenly or gradually to renal failure. In this event, a number of symptoms, signs, or laboratory findings point to the diagnosis.
The following is a brief list of the symptoms of kidney failure:
- weakness
- lethargy
- shortness of breath
- widespread edema (swelling due to fluid retention)
- metabolic acidosis or alkalosis
- heart arrhythmias
- loss of appetite
- uremia (high levels of urea, a metabolic waste, in the blood)
- fatigue
- excessive or too little urination
Glomerular Filtration Rate (GFR)
The volume of filtrate formed by both kidneys per minute is termed the glomerular filtration rate (GFR). The heart pumps about 5 L blood per min under resting conditions. Approximately 20 percent or one liter enters the kidneys to be filtered. On average, this liter results in the production of about 125 mL/min filtrate produced in males (range of 90 to 140 mL/min) and 105 mL/min filtrate produced in females (range of 80 to 125 mL/min). This amount equates to a volume of about 180 L/day in males and 150 L/day in females. Ninety-nine percent of this filtrate is returned to the circulation by reabsorption so that only about 1–2 liters of urine are produced per day (Table \(\PageIndex{2}\)).
| Flow per minute (mL) | Calculation | |
|---|---|---|
| Renal blood flow | 1050 | Cardiac output is about 5000 mL/minute, of which 21 percent flows through the kidney. 5000*0.21 = 1050 mL blood/min |
| Renal plasma flow | 578 | Renal plasma flow equals the blood flow per minute times the hematocrit. If a person has a hematocrit of 45, then the renal plasma flow is 55 percent. 1050*0.55 = 578 mL plasma/min |
| Glomerular filtration rate | 110 | The GFR is the amount of plasma entering Bowman’s capsule per minute. It is the renal plasma flow times the fraction that enters the renal capsule (19 percent). 578*0.19 = 110 mL filtrate/min |
| Urine | 1296 ml/day | The filtrate not recovered by the kidney is the urine that will be eliminated. It is the GFR times the fraction of the filtrate that is not reabsorbed (0.8 percent). 110*.008 = 0.9 mL urine /min Multiply urine/min times 60 minutes times 24 hours to get daily urine production. 0.9*60*24 = 1296 mL/day urine |
It is vital that the flow of blood through the kidney be at a suitable rate to allow for filtration. This rate determines how much solute is retained or discarded, how much water is retained or discarded, and ultimately, the osmolarity of blood and the blood pressure of the body.
Regulation of Glomerular Filtration Rate
GFR needs to be maintained at a constant level as too much or too little filtration can have negative effects on the body. Too much filtration may result in excessive fluid loss, while too little filtration may result in wastes building up in the blood. The following describes the variety of ways the body regulates the GFR.
Sympathetic Nerves
The kidneys are innervated by the sympathetic neurons of the autonomic nervous system via the celiac plexus and splanchnic nerves. Reduction of sympathetic stimulation results in vasodilation and increased blood flow through the kidneys during resting conditions. When the frequency of sympathetic stimulation increases, the smooth muscles surrounding the afferent arteriole constricts (vasoconstriction), resulting in diminished blood flow into the glomerulus, so less filtration occurs. Under conditions of stress, sympathetic nervous activity increases, resulting in the direct vasoconstriction of afferent arterioles (norepinephrine effect) as well as stimulation of the adrenal medulla. The adrenal medulla, in turn, produces a generalized vasoconstriction through the release of epinephrine. This includes vasoconstriction of the afferent arterioles, further reducing the volume of blood flowing through the kidneys. This process redirects blood to other organs with more immediate needs. If blood pressure falls, the sympathetic nerves will also stimulate the release of renin, an enzyme that leads to the increase of blood pressure.
Autoregulation
The kidneys are very effective at regulating the rate of blood flow over a wide range of blood pressures. Your blood pressure will decrease when you are relaxed or sleeping. It will increase when exercising. Yet, despite these changes, the filtration rate through the kidney will change very little. This is due to two internal autoregulatory mechanisms that operate without outside influence: the myogenic mechanism and the tubuloglomerular feedback mechanism.
Arteriole Myogenic Mechanism
The myogenic mechanism regulating blood flow within the kidney depends upon a characteristic shared by most smooth muscle cells of the body. When you stretch a smooth muscle cell, it contracts; when you stop, it relaxes, restoring its resting length. This mechanism works in the afferent arteriole that supplies the glomerulus. GFR must be maintained at a constant rate, it must not be too high or too low. If GFR went up every time your blood pressure went up, excessive filtrate would be produced. The myogenic mechanism acts to counteract this. When blood pressure increases, smooth muscle cells in the wall of the arteriole are stretched and respond by contracting which constricts the blood vessels. This reduces blood flow into the glomerulus. By reducing blood flow into the glomerulus, GFR can be maintained at a constant rate, rather than it increasing due to an increase in systemic blood pressure. When blood pressure drops after an increase, the same smooth muscle cells relax, allowing the afferent arteriole to dilate, allowing a continued even flow of blood.
Tubuloglomerular Feedback
The tubuloglomerular feedback mechanism involves the JGA and a signaling mechanism between its components. Recall that the JGA is made up of the juxtaglomerular cells, the macula densa and the afferent arteriole as seen in Figure \(\PageIndex{1}\). This mechanism stimulates either constriction or dilation of the afferent arteriole (Table \(\PageIndex{1}\). Recall that the distal convoluted tubule (DCT) is in intimate contact with the afferent and efferent arterioles of the glomerulus. Specialized macula densa cells in this segment of the tubule respond to changes in the fluid flow rate and Na+ concentration. As GFR increases, there is less time for NaCl to be reabsorbed (returned to the blood) in the proximal convoluted tubule (PCT), resulting in higher osmolarity in the filtrate. This increased solute concentration of the forming urine, and the greater flow rate within the DCT, activates macula densa cells to respond by releasing signaling molecules. These signaling molecules stimulate the afferent arteriole to constrict, slowing blood flow and reducing GFR. Conversely, when GFR decreases, less Na+ is in the forming urine, and most will be reabsorbed before reaching the macula densa, which will result in decreased signaling molecules, allowing the afferent arteriole to dilate and increase GFR.
| Change in GFR | NaCl Absorption | Effect on GFR |
|---|---|---|
| Increased GFR | Tubular NaCl increases | Vasoconstriction slows GFR |
| Decreased GFR | Tubular NaCl decreases | Vasodilation increases GFR |
