69 Intrinsic control of GFR
Learning Objectives
- With respect to autoregulation, describe the myogenic and tubuloglomerular feedback mechanisms and explain how they affect urine volume and composition
- Explain the role of the juxtaglomerular apparatus (JGA) in tubuloglomerular feedback.
Glomerular filtration has to be carefully and thoroughly controlled because the simple act of filtrate production can have huge impacts on body fluid homeostasis and systemic blood pressure. Due to these two very distinct physiological needs, the body employs two very different mechanisms to regulate GFR. The kidney can control itself locally through intrinsic controls, also called renal autoregulation. These intrinsic control mechanisms maintain filtrate production so that the body can maintain fluid, electrolyte, and acid-base balance and also remove wastes and toxins from the body. There are also control mechanisms that originate outside of the kidney, the nervous and endocrine systems, and are called extrinsic controls. The nervous system and hormones released by the endocrine systems function to control systemic blood pressure by increasing or decreasing GFR to change systemic blood pressure by changing the fluid lost from the body.
Intrinsic Controls: Renal 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. The kidney’s ability to autoregulate can maintain GFR with a MAP of as low as 80 mm Hg to as high as 180 mm Hg. 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 and can regulate the blood flow into the glomerulus. When blood pressure increases, smooth muscle cells in the wall of the arteriole are stretched and respond by contracting to resist the pressure, resulting in little change in flow. This vasoconstriction of the afferent arteriole acts to reduce excess filtrate formation, maintaining normal NFP and GFR. Reducing the glomerular pressure also functions to protect the fragile capillaries of the glomerulus. When blood pressure drops, the same smooth muscle cells relax to lower resistance, increasing blood flow. The vasodilation of the afferent arteriole acts to increase the declining filtrate formation, bringing NFP and GFR back up to normal levels.
Tubuloglomerular Feedback
The tubuloglomerular feedback mechanism involves the juxtaglomerular (JG) cells, or granular cells, from the juxtaglomerular apparatus (JGA) and a paracrine signaling mechanism utilizing ATP and adenosine. These juxtaglomerular cells are modified, smooth muscle cells lining the afferent arteriole that can contract or relax in response to the paracrine secretions released by the macula densa. This mechanism stimulates either contraction or relaxation of afferent arteriolar smooth muscle cells, which regulates blood flow to the glomerulus (Table 25.8). Recall that the 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 in the PCT, resulting in higher osmolarity in the filtrate (hyperosmotic). The increased fluid movement more strongly deflects single nonmotile cilia on macula densa cells. This increased osmolarity of the filtrate, and the greater flow rate within the DCT, activates macula densa cells to respond by releasing ATP and adenosine (a metabolite of ATP). ATP and adenosine act locally as paracrine factors to stimulate the myogenic juxtaglomerular cells of the afferent arteriole to constrict, slowing blood flow into the glomerulus. This vasoconstriction causes less plasma to be filtered, which decreases the glomerular filtration rate (GFR), which gives the tubule more time for NaCl reabsorption. Conversely, when GFR decreases, less NaCl is in the filtrate, and most will be reabsorbed before reaching the macula densa, which will result in decreased ATP and adenosine, allowing the afferent arteriole to dilate and increase GFR. This vasodilation causes more plasma to be filtered, which increase the glomerular filtration rate (GFR), which gives the tubule less time for NaCl reabsorption increasing the amount of NaCl in the filtrate.
| Paracrine Mechanisms Controlling Glomerular Filtration Rate (Table 25.8) | |||
|---|---|---|---|
| Change in GFR | NaCl Absorption | Role of ATP and adenosine/Role of NO | Effect on GFR |
| Increased GFR | Tubular NaCl increases | ATP and adenosine increase, causing vasoconstriction | Vasoconstriction slows GFR |
| Decreased GFR | Tubular NaCl decreases | ATP and adenosine decrease, causing vasodilation | Vasodilation increases GFR |
Adapted from Anatomy & Physiology by Lindsay M. Biga et al, shared under a Creative Commons Attribution-ShareAlike 4.0 International License, chapter 25
