Question

Discuss the structure and function of the juxtaglomerular apparatus. What factors determine GFR? Why is it so important to keep GFR stable? Explain in terms of nephron function. Briefly describe the autoregulatory mechanisms used in the kidney to maintain GFR on an ongoing basis.

Answer 1

Juxtamedullary apparatus maintains the filtration rate in the kidneys. It is also involved in blood pressure regulation as well. It mainly contains thick ascending limb, macula densa the afferent arteriole that bring blood to the kidneys. This apparatus is located near the glomerulus at the vascular pole. The Macula densa is an epithelial layer that senses the sodium levels in the kidney filtrate that enters the tubule. When there are high concentration of sodium detected, the macula densa well cause efferent arteriole smooth muscle contraction in order to reduce blood flow to the glomerulus. This will reduce the glomerular filtration rate (GFR). The juxtamedullary cells present in the glomerulus also secrete renin to increase blood pressure. The juxtamedullary cells also have the lacis cells (extraglomerular mesangial cells), that are long elongated cells. The lacis cells are located near the macula densa and have a presently unknown function.

Glomerular filtration rate is the rate at which the blood flows through the kidneys and is filtered. GFR is determines by the renal blood flow and glomerular capillary hydrostatic pressure. The afferent arteriole receives 20-25% of the cardiac output. Molecules less than 70nM are allow to pass through the capillaries of the fenestrated epithelium membrane. Molecules of approximately 1kDa,a are allowed to pass through the basement membrane which only allows cation to flow through on account of their negative charges. Podocytes allow the size selection of 14nM via their foot processes. The glomerular hydrostatic pressure or the blood pressure in the glomerulus will favor filtration along with oncotic pressure (pressure via colloidal proteins) in Bowman’s capsule. Hydrostatic pressure in Bowman’s capsule and oncotic pressure in the Glomerular capillaries will oppose glomerular filtration.

Stability of GFR is required to maintain the kidney function. A reduction in GFR indicates damage to the nephrons of the kidneys and is seen as a measure of different levels of chronic kidney disease. A low GFR indicates that there is less blood flow to the kidneys which indicates less filtration by the glomerulus. Normal GFR is 100-140 mls/min. Less than 90 mls/min indicates mild damage while less than 30 mls/ min indicates chronic kidney damage where the kidneys are not functional at all. The kidneys will try to increase reabsorption in remaining nephrons when GFR falls. However, this will put excess pressure on the remaining nephrons. Kidney nephrons allow excretion of wastes such as urea and ammonia are excreted. Conversely, sodium, glucose, calcium and other ions along with water are reabsorbed by the renal tubules from the filtrate. Both reabsorption and excretion depends on the GFR. If blood flow to kidneys is reduced, there will be reduced glomerular filtration. Stable renal blood flow will also provide the nephrons with oxygen and ATP for smooth functioning. The amount of filtrate in the renal tubules will be reduced, affecting the reabsorption as well as excretion of nutrients and waster production. As a result, the kidneys will stop functioning, causing kidney damage. Hence, it is absolutely essential to maintain a stable GFR to ensure smooth functioning of the nephron and ultimately of the kidneys.

Regulation of GFR:

1. Blood pressure: Increased hydrostatic pressure (high blood pressure) induces a stretch in the smooth muscles of the afferent arteriole, resulting in activation of inward directed ion channels. There will be muscle contraction due to depolarization, which will maintain the renal blood flow by decreasing it. Thus, the kidneys are not damaged. In case of low blood pressure, there is afferent arteriole dilation due to decreased stretch. This will increase renal blood flow and maintain kidney function.

2. Renin-angiotensin-aldosterone system (RAAS): Renin is secreted by juxtamedullary cells in afferent arteriole in response to decreased stretch (low blood pressure). Renin activates angiotensinogen in blood to angiotensin I, which is converted to angiotensin II by angiotensin converting enzyme (ACE) in lungs. Angiotensin II causes adrenal cortex to secrete aldosterone, which then increases reabsorption of sodium and water an excretion of potassium. This will maintain GFR due to preservation of renal perfusion. Opposite effect causing reduced renin and aldosterone secretion occurs in high blood pressure.

3. Tubuloglomerulo-feedback: Macula densa in the thick ascending limb of the distal tubules are sensors of increase in GFR. They sense GFR by sensing the increased sodium ions in the filtrate, which increases chloride ion concentration in intracellular compartment. There is depolarization, which causes production of ATP, adenosine and thromboxane. These paracrine mediators will cause the smooth muscle contraction in afferent arterioles. Afferent arteriole contraction will decrease renal blood flow and maintain GFR to normal levels. Macula densa can also stimulate renin secretion that stimulates the RAAS system in kidneys to maintain GFR.