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Schematic depicting how the RAAS works. Here, activation of the RAAS is initiated by a low perfusion pressure in the juxtaglomerular apparatus
Renal corpuscle. Juxtaglomerular apparatus is "D".

The juxtaglomerular apparatus is a microscopic structure in the kidney, which regulates the function of each nephron. The juxtaglomerular apparatus is named for its proximity to the glomerulus: it is found between the vascular pole of the renal corpuscle and the returning distal convoluted tubule of the same nephron. This location is critical to its function in regulating renal blood flow and glomerular filtration rate. The three cellular components of the apparatus are the macula densa, extraglomerular mesangial cells, and juxtaglomerular cells (also known as granular cells).

Contents

Cells of the Juxtaglomerular Apparatus

There are 3 different types of cells in the Juxtaglomerular Apparatus: Granular Cells, Mesangial Cells and Macula Densa Cells.

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Granular Cells

These are modified pericytes of glomerular arterioles. They are also known as Juxtaglomerular cells.

The granular cells secrete renin in response to:

  • Beta1 adrenergic stimulation
  • Decrease in renal perfusion pressure (detected directly by the granular cells)
  • Decrease in NaCl absorption in the Macula Densa (often due to a decrease in glomerular filtration rate, or GFR).

Macula Densa Cells

Macula densa cells are columnar epithelium thickening of the distal tubule. The macula densa senses sodium chloride concentration in the distal tubule of the kidney and secretes a locally active (paracrine) vasopressor which acts on the adjacent afferent arteriole to decrease glomerular filtration rate (GFR), as part of the tubuloglomerular feedback loop. Specifically, excessive filtration at the glomerulus or inadequate sodium uptake in the proximal tubule / thick ascending loop of Henle brings fluid to the distal convoluted tubule that has an abnormally high concentration of sodium. Na/Cl cotransporters move sodium into the cells of the macula densa. The macula densa cells do not have enough basolateral Na/K ATPases to excrete this added sodium, so the cell's osmolarity increases. Water flows into the cell to bring the osmolarity back down, causing the cell to swell. When the cell swells, a stretch-activated non-selective anion channel is opened on the basolateral surface. ATP escapes through this channel and is subsequently converted to adenosine. Adenosine vasoconstricts the afferent arteriole via A1 receptors and vasodilates (to a lesser degree) efferent arterioles via A2 receptors which decreases GFR. Also, when macula densa cells detect higher concentrations of Na and Cl they inhibit Nitric Oxide Synthetase (decreasing renin release).

A decrease in GFR means less solute in the tubular lumen. As the filtrate reaches the macula densa, less NaCl is re-absorbed. The macula densa cells detect lower concentrations in Na and Cl and upregulate Nitric Oxide Synthetase (NOS). NOS creates NO which catalyses the formation of prostaglandins. These prostaglandins diffuse to the granular cells and activate a prostaglandin specific Gs receptor. This receptor activates adenylate cyclase which increases levels of cAMP. cAMP augments renin release.

Mesangial cells

Mesangial cells are structural cells in the glomerulus that under normal conditions serve as anchors for the glomerular capillaries. The mesangial cells within the glomerulus communicate with mesangial cells outside the glomerulus (extraglomerular mesangial cells), and it is the latter cells that form part of the juxtaglomerular apparatus. These cells form a syncytium and are connected with glomerular mesangial cells via gap junctions.

The function of the extraglomerular mesangial cells remains somewhat mysterious. They contain actin and myosin, allowing them to contract when stimulated by renal sympathetic nerves, which may provide a way for the sympathetic nervous system to modulate the actions of the juxtaglomerular apparatus. The latest thinking is that in times of great sympathetic discharge [i.e. during periods when the blood pressure is low, e.g. from blood loss ], mesangial contraction reduces the surface area of the glomerulae, thus reducing glomerular filtration and saving excess fluid from being lost into the urine. In addition, extraglomerular mesangial cells are strategically positioned between the macula densa and the afferent arteriole, and may mediate signalling between these two structures.[1]

See also

References

  1. ^ Goligorsky MS, Iijima K, Krivenko Y, Tsukahara H, Hu Y, Moore LC. Role of mesangial cells in macula densa to afferent arteriole information transfer. Clin Exp Pharmacol Physiol. 1997 Jul;24(7):527-31.

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