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 (juxtaglomerular cells are not granular cells
but are granulated as they release Renin). Cells of the Juxtaglomerular Apparatus There are 3 different types of cells in the
Juxtaglomerular Apparatus: Granular Cells,
Macula Densa Cells, and Mesangial Cells. Granular Cells Granular cells are modified pericytes of
glomerular arterioles. They are also known
as Juxtaglomerular cells.. The Juxtaglomerular 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, causing slower filtrate movement
through the proximal tubule and thus
more time for reabsorption. This results
in a lower NaCl concentration by the
time the filtrate reaches the Macula
Densa). 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, adenosine inhibits
renin release in JG cells via A2 receptors on
JG cells using Gi pathway. Also, when macula densa cells detect higher
concentrations of Na and Cl they inhibit
Nitric Oxide Synthetase (decreasing renin
release) with an unknown pathway. 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. Prostaglandins and NO also
makes a vasadilator effect on afferent
arteriol but this doesn't happen on efferent
arteriol due to 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.
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