‫ زيـد قـيـس عـبـد الحسين‬:‫اإلســم‬

B2 :‫المجموعة‬
Kidney and Nephron
The kidneys are a pair of bean-shaped structures that are located just
below and posterior to the liver in the peritoneal cavity. Adrenal glands,
also called suprarenal glands, sit on top of each kidney. Kidneys regulate
the osmotic pressure of a mammal’s blood through extensive filtration
and purification in a process known as osmoregulation. All the blood in
the human body is filtered many times a day by the kidneys. These organs
use almost 25 percent of the oxygen absorbed through the lungs to
perform this function. Oxygen allows the kidney cells to efficiently
manufacture chemical energy in the form of ATP through aerobic
respiration. Kidneys eliminate wastes from the body; urine is the filtrate
that exits the kidneys.

Kidneys’ location and function: Kidneys filter the blood, producing

urine that is stored in the bladder prior to elimination through the urethra.
They are located in the peritoneal cavity.
Externally, the kidneys are surrounded by three layers. The outermost
layer, the renal fascia, is a tough connective tissue layer. The second
layer, the perirenal fat capsule, helps anchor the kidneys in place. The
third and innermost layer is the renal capsule. Internally, the kidney has
three regions: an outer cortex, a medulla in the middle, and the renal
pelvis in the region called the hilum of the kidney. The hilum is the
concave part of the bean-shape where blood vessels and nerves enter and
exit the kidney; it is also the point of exit for the ureters.

The nephron is the functional unit of the kidney. The glomerulus and
convoluted tubules of the nephron are located in the cortex of the kidney,
while the collecting ducts are located in the pyramids of the kidney’s
medulla.
A nephron consists of three parts: a renal corpuscle, a renal tubule, and
the associated capillary network, which originates from the cortical
radiate arteries. The renal corpuscle, located in the renal cortex, is
composed of a network of capillaries known as the glomerulus, as well as
a cup-shaped chamber that surrounds it: the glomerular or Bowman’s
capsule.
The renal tubule is a long, convoluted structure that emerges from the
glomerulus. It can be divided into three parts based on function. The first
part is called the proximal convoluted tubule (PCT), due to its proximity
to the glomerulus. The second part is called the loop of Henle, or
nephritic loop, because it forms a loop (with descending and ascending
limbs) that goes through the renal medulla. The third part of the renal
tubule is called the distal convoluted tubule (DCT); this part is also
restricted to the renal cortex. This last part of the nephron connects with
and empties its filtrate into collecting ducts that line the medullary
pyramids. The collecting ducts amass contents from multiple nephrons,
fusing together as they enter the papillae of the renal medulla.
GFR
Glomerular filtration rate (GFR) represents the flow of plasma
from the glomerulus into Bowman’s space over a specified period and is
the chief measure of kidney function. The kidneys receive 20% to 25% of
the cardiac output (about 1.0 to 1.1 liters per minute) with the blood
entering individual glomerular tufts via the afferent arteriole and exiting
through the efferent arteriole. Of this renal blood flow (RBF), only the
plasma can cross the structures comprising the glomerulus. Thus, the
renal plasma flow (RPF) is a more accurate expression and is calculated
as follows: RBF*(1-Hct)
The RPF is approximately 600 to 720 ml per minute. Within the plasma,
organic and inorganic solutes are freely filtered- meaning that they can be
found in the ultrafiltrate (the fluid in Bowman’s space) and plasma at the
same concentrations. GFR is approximately 120 ml per min (180 L per
day). Average urine output, on the other hand, averages only about 1.5 L
daily. The reabsorption of 178.5 L requires a sophisticated tubular
network.
The structure of the glomerulus exerts both size and charge constraints
over what will pass through. The endothelium of fenestrated capillaries
permits molecules of less than 70 nM to pass through. The basement
membrane also restricts by size (approximately 1 kDa) and by charge,
since the negative charge of basement membrane protein repels other
proteins but favors filtration of cations. Finally, podocyte food processes
on the visceral layer also size selects by about 14 nM.
The forces that govern filtration in the glomerular capillaries are the same
as any capillary bed. Capillary hydrostatic pressure (Pc) and Bowman’s
space oncotic pressure (πi) favor filtration into the tubule, and Bowman’s
space hydrostatic pressure (Pi) and capillary-oncotic pressure (πc) oppose
filtration. These terms are expressed together in the Starling force’s law
equation, as a measure of J (flow):
 J = Kf ([Pc-Pi] - σ [πc - πi])
Where Kf is the filtration coefficient, and σ is the reflection coefficient,
both inherent and fixed values of the epithelium. For the kidney, flow (J)
is positive, favoring filtration, meaning that plasma flows from higher
hydrostatic pressure in the capillary to lower hydrostatic pressure in the
tubular space, despite the unfavorable oncotic gradient (there is higher
protein concentration in the capillary). In theory, therefore, GFR is highly
dependent on hydrostatic pressure.
However, GFR is tightly regulated through several mechanisms. Firstly,
RBF is relatively constant over a wide range of mean arterial pressures
(MAP), through what is termed the myogenic response. An increase in
hydrostatic pressure in the afferent arteriole stretches vascular smooth
muscle, activating inward directed ion channels, leading to depolarization
and contraction. This prevents pathologic increases in RBF that would
damage the kidney. Notably, this is a localized effect, independent of
autonomic regulation (as is the case for autoregulation in other organs).
Falling blood pressure does the opposite: dilate the afferent arteriole and
preserve blood flow to the kidney. Secondly, the renin-angiotensin-
aldosterone system acts to preserve GFR. The juxtaglomerular cells in the
afferent arteriole release renin in response to decreased stretch.
Circulating renin activates liver-synthesized angiotensinogen to
angiotensin I, which is further acted upon by angiotensin converting
enzyme in the lung to the active angiotensin II, a potent vasoconstrictor.
Angiotensin II raises systemic blood pressure and stimulates the release
of aldosterone, which promotes sodium retention/potassium secretion and
further increases in blood pressure, in both cases preserving renal
perfusion and maintaining GFR. The third mechanism is
tubuloglomerular feedback. The macula densa in the thick ascending limb
senses an increase in GFR through increased delivery of electrolytes. The
increased flow leads to an increased intracellular Cl concentration (sensed
by Na-K-Cl transporter), depolarizing the cell, and leading to the release
of ATP, adenosine, and thromboxane. These paracrine mediators contract
nearby smooth muscle cells in the afferent arteriole to reduce RBF and,
thus, return GFR to normal. The macula densa can also independently
stimulate the juxtaglomerular cells to release renin, activating the RAAS.
We know that this transporter is implicated because the effect can be
attenuated by loop diuretics that block the Na-K-Cl channel.