Download Kidneys- complete!

Urinary
I. Introduction and anatomical features
A. Introduction: The kidneys receive blood from the renal artery. The renal artery
branches into a series of capillary beds. Those capillary beds are surrounded by a cup
that leads to a tube. Here, some plasma is squeezed out of the capillaries; it is captured
by the cup and then sent into the tube. Lining the tube are cells, one single layer of cells.
These cells examine the subset of plasma and decide what is waste and what is valuable.
Anything that is NOT waste will be plucked out of the tube and returned to the blood by
these cells. Anything that IS waste stays in the tube. The kidneys contain millions of
these “cup and tube” devices. All of the tubes lead to the collecting area of the kidney,
which leads to the ureter. The “cup and tube” devices are called nephrons. The “cup”
part of the nephron is called Bowman’s Capsule.
Terms: filtration, reabsorption, secretion
B. Blood supply to the kidneys- the renal artery enters at the hilus. It branches
into the interlobar arteries that travel through the columns, they branch further, leading to
the afferent arterioles that enter the Bowman’s capsule of each nephron. The afferent
arterioles branch into a capillary bed called a glomerulus within the Bowman's capsule.
The glomerulus merges back into the efferent arteriole which leaves Bowman’s capsule.
The efferent arteriole branches again into the peritubular capillaries and vasa recta
(also capillaries) which wrap around the tubules of the nephron.
The peritubular capillaries merge into venules, which merge into the interlobar veins. The
interlobar veins merge into the renal vein, which leaves the kidney at the hilus.
C. Nephrons- this is where fluid (a subset of plasma) leaves the blood, and urine
is produced by returning nutrients to blood, and keeping waste products out of the blood.
1. The "entrance" to a nephron- where blood fluid enters: the renal
corpuscle
a. Blood plasma enters each nephron in a little capsule called
Bowman's capsule. It contains a double layer of epithelium. The inner
(visceral) layer lines the glomerulus (capillary bed). The outer (parietal)
layer forms the outer wall, and is continuous with a tubule that will carry
blood fluids away. This is similar to the serous membranes we've
discussed, in that it resembles a balloon with a fist pushed into it (in this
case, the glomerulus is the "fist"), and there is a fluid-filled space between
the layers. This space is called the capsular space.
b. The glomerulus is a ball of capillaries within Bowman's capsule.
The afferent arteriole brings blood into the glomerulus, and the efferent
arteriole carries blood away from it. The glomerular capillaries are
fenestrated, and they are surrounded by a basement membrane.
c. The filtration membrane- blood fluid is forced across the
fenestrated capillaries, the basement membrane, and between the filtration
slits into the capsular space. These three layers, collectively, are called the
filtration membrane. Each layer is more restrictive in terms of the size of
particles it will let cross. For example, the fenestrated capillaries allow
most proteins to cross, but the filtration slits allow no proteins to cross.
The filtration membrane allows most plasma solutes, but not proteins, to
pass into the capsular space. Proteins are among the largest molecules in
the plasma. Red blood cells are way too huge to cross the filtration
membrane.
The subset of plasma that has entered the nephron is now called filtrate.
2. The tubules- receive filtrate from the renal corpuscle. Peritubular and vasa recta
capillaries wrap around the tubules. As filtrate travels through the tubules,
substances we don't want to get rid of (ex., glucose and amino acids) are
reabsorbed (returned to the blood). In addition, some undesired substances in the
blood are moved into the tubules for excretion (secreted). Each section has a
different function, which is reflected in their anatomy and permeability to specific
substances.
Keep in mind that when a cell is permeable to a substance, like water or Na+, that
means the cell has channels that specifically let that substance through. The only
substances that don't need channels are relatively small and relatively uncharged.
a. The Proximal Convoluted Tubule- receives filtrate from the
renal corpuscle. Simple cuboidal with microvilli.
Most reabsorption and secretion of solutes occurs here
b. Loop of Henle- filtrate moves from the PCT to the loop of
Henle, which includes the descending and ascending limbs, as well as the
thin portions (descending and part of the ascending) and thick portion
(part of the ascending). For simplification, we will use descdening and
thin interchangeably, and ascending and thick interchangeably.
i. The descending loop (thin segment)- Simple squamous,
no microvilli
permeable to water but not to solutes
most water reabsorption occurs here
ii. The ascending loop (thick segment)Cuboidal with sparce microvilli
Not permeable to water but permeable to solutes, especially
Na+, ClLots of Na+ reabsorption occurs here
c. Distal Convoluted Tubule
Simple Cuboidal, sparce microvilli
Reabsorption and secretion of some solutes and water,
particularly under the influence of hormones. Notably, Na+
and Ca++ reabsorption.
d. Collecting ducts
Similar to DCT- reabsorption and secretion, influenced by
hormones.
Two cell populations. One cell type responsible for H2O
and Na+ reabsorption and urea secretion. The other cell type
responsible for H+ and HCO3- reabsorption or secretion (acid-base
balance).
3. Juxtaglomerular Apparatus- Region of the nephron where the DCT gets
sandwiched between the afferent and efferent arterioles. In this area, the afferent
arteriole and the DCT contain specialized cells that help to maintain filtration
pressure.
a. Afferent arteriole contains Juxtaglomerular (JG) cells, which
secrete renin, and act as mechanoreceptors that monitor stretch (blood
pressure).
b. DCT contains macula densa, a group of specialized cells
adjacent to the JG cells, and act as chemoreceptors and mechanoreceptors
that monitor solute concentration and flow rate of the solute. Macula densa
cells cause autoregulatory constriction and dilation of the arterioles.
II. Kidney Physiology
A. Glomerular Filtration
1. Net Filtration Pressure- Hydrostatic pressure of blood entering the
glomerulus pushes fluid out of the capillaries and into the Bowman's capsule.
Like filtration at other capillaries, it is opposed by other pressures (for instance,
osmotic pressure).
After all opposing pressures are considered, the average Net Filtration
Pressure is about 10 mmHg, and fluid moves out of the glomerulus. This pressure
is just perfect to get a good balance of getting enough wastes into the tubules,
without pushing too much good stuff out of the blood or damaging the filtration
membrane.
2. Glomerular Filtration Rate- The amount of filtrate formed per minute.
The GFR is directly proportional to the NFP. Another reason the NFP is carefully
maintained is that if the GFR is too high (that is, too much fluid leaves the blood),
the tubules will be overloaded and won't have enough time to reabsorb all the
desired materials back into the blood.
3. Regulation of Glomerular Filtration- Again, the NFP and GFR must be
carefully maintained to make sure that enough wastes are removed from the
blood, and enough nutrients are recovered to the blood. This is accomplished
through autoregulation, hormonal controls, and sympathetic stimulation.
Filtration Pressure is maintained by constricting or dilating the afferent
and efferent arterioles. To increase Filtration Pressure, the afferent arteriole can
be dilated, the efferent arteriole can be constricted, or both. To decrease Filtration
Pressure, the opposite is true. So, if blood pressure rises, for instance, the afferent
arteriole could constrict to make sure that the NFP does not rise much above 10
mmHg, and vice versa.
a. Autoregulation- this occurs continuously to maintain
NFP/GFR, with small adjustments constantly compensating for small
changes in blood pressure. Smooth muscle of the arterioles responds
automatically, and macula densa cell secretions affect this as well.
b. Neuroendocrine Control- these are more concerned with tissue
perfusion of the REST of the body, and will cause the kidneys to adjust
NFP/GFR to help out; ie, GFR may be increased or reduced to help adjust
general body blood pressure. Kidneys will sacrifice GFR, either increase
it or decrease it, if needed to help out with the rest of the body.
i. The Renin-AngiotensinII mechanism- When pressure
coming into the afferent arteriole drops substantially enough, this
indicates a drop in general body pressure and JG cells secrete
renin. Review renin from the vessels chapter! Angiotensin II
causes constriction of both afferent and efferent arterioles, and
some blood will be shunted away from kidneys. GFR may be
slightly reduced.
ii. Atrial Natriuretic Peptide- When pressure in the atria of
the heart increases, ANP is released. At the kidneys, ANP causes
the afferent arterioles to dilate and the efferent arteriole to
constrict. This actually increases NFP/GFR, but by doing so causes
increased urine output (and subsequent loss of water thereby
lowering blood pressure).
iii. Sympathetic influence- a severe sympathetic activation
shunts blood away from kidneys by causing both arterioles to
constrict. Reduces GFR. Also causes JG cells to secrete renin.
B. Tubular Reabsorption and secretion- Again, solutes and water are purposefully
reabsorbed or secreted once filtrate gets to the tubules. This is accomplished by channels
embedded in the membranes of cells lining the tubules.
1. Mechanisms for moving solutes to or from the blood include:
Passive diffusion through channels (water)
Facilitated diffusion
Active transport
Coupled transport: some examples- Na+ and K+
(countertransport), HCO3- and Cl- (countertransport), Na+ and
glucose (cotransport)
2. Since reabsorption of water-soluble substances depends on transport
through channels, the amount of a substance that can be reabsorbed is dependent
on the number of channels available. If the amount of a substance exceeds the
number of channels available to reabsorb it, then some will end up in the urine.
For example, if you take a multi-vitamin B supplement, you will urinate most of
the B6 molecules. That’s because the amount of B6 molecules greatly exceeds
the number of channels available for its reabsorption. The number of channels
available to reabsorb specific substances is called the transport max. Glucose
almost never exceeds its transport max in healthy individuals, so urine tests for
glucose can indicate problems.
Proteins should not be present in the urine either, but for a different reason; why is that?
C. Absorptive capabilities of the tubules- I covered most of this already (see
tubule section in anatomy), so I'll just add a little more info on some.
1. PCT- again, highly permeable to most solutes and water. Most solute
reabsorption and secretion occurs here, and by the time filtrate reaches the loop of
Henle, virtually all glucose and amino acids have been reclaimed to the blood.
2. Loop of Henle- The thin segment is responsible for most water
reabsorption, and the thick segment is responsible for Na+ and Cl- reabsorption
(which drives the reabsorption of water in the thin segment, as we will see soon).
3. DCT and Collecting ducts- Further reabsorption and secretion occurs
here, and these tubules are especially sensitive to hormonal input. Notably,
i. Aldosterone- causes tubule cells to build Na+ - K+ countertransport channels. In this case, Na+ is reabsorbed to the blood. Indirectly,
aldosterone causes water retention because water "follows" Na+. So,
aldosterone causes the reabsorption of Na+ and water, and the secretion of
K+. (Promotes Na+ and water conservation)
ii. ADH- causes tubule cells to build water channels. This allows
more water to be reabsorbed to the blood. (Promotes water conservation)
iii. PTH and calcitriol- cause tubule cells to build (or open) Ca++
channels, increasing Ca++ reabsorption. (Promotes Ca2+ conservation)
iv. H+ and HCO3- reabsorption and secretion can also be adjusted
here, helping to maintain blood pH. No hormone needed here; we’ll
revisit with electrolytes.
4. Back to the Loop of Henle: the Counter Current Mechanism, how water
is reabsorbed. The water channels in cells are always open. So, cells cannot
actively "pump" water in the desired direction. Therefore, they use the principle
of osmosis to direct water movement. Remember that osmosis predicts that water
will move from a hypotonic solution to a hypertonic solution. So, if you are a cell,
and you "want" water to move in a particular direction, you can establish a
gradient of solute concentration and water will follow that gradient. That's exactly
what cells of the thick segment of the loop of Henle do. We'll start there.
The thick segment of the loop of Henle is completely impermeable to water. In this
section, cells pump Na+ and Cl- into the interstitium (or peritubular space). Na+ and Clbuild up in the peritubular space, which becomes quite concentrate. In fact, it becomes
hypertonic to the filtrate in the thin segment.
Now we will back up a bit, and look at filtrate entering the thin segment. The thin
segment is right next to the thick segment, and they share peritubular space. Remember
that the thin segment is highly permeable to water. Fluid entering the thin segment is
suddenly thrown into highly hypertonic surroundings. Water gets sucked right out of the
thin segment, moving passively by osmosis.
At this point, we've gotten water to leave the tubules and enter the interstitium. But we
still need to get it back to the blood. A network of capillaries wraps around the loop, the
vasa recta. Blood in these capillaries moves in the opposite direction as filtrate in the
loop. Now we need to go back to the thick segment of the ascending loop. Here, blood is
traveling down the peritubular capillaries. Cells of the thick segment are busy pumping
out Na+ and Cl-, and blood entering this area enters a very concentrate environment.
Instead of letting water go, the peritubular capillaries instead let Na+ and Cl- enter. So, as
blood enters this concentrate environment, Na+ and Cl- rush into the blood, and it
becomes very concentrate. As it travels down the loop, blood absorbs more and more
Na+ and Cl-.
Then, the capillaries wrap around the base of the loop and blood travels up, past the
descending, thin segment. Here, the blood is so concentrate that it is in fact hypertonic to
the peritubular space (interstitium). At any given point along the descending loop, blood
in the adjacent peritubular capillaries is hypertonic to the peritubular space. And recall,
the peritubular space is hypertonic to the filtrate. So, along the descending loop water
leaves the filtrate by osmosis. Since the blood is even MORE hypertonic, water just keeps
on going and moves right into the blood, which is carried completely away.
So, along the descending, thin segment of the loop of Henle, at any given point the
peritubular space is hypertonic to the filtrate, and blood in the adjacent peritubular
capillaries is hypertonic to the peritubular space. Water moves by osmosis straight from
the filtrate into the blood. Voila, water is reabsorbed.
Now, take a few moments to draw this process out. Start with the thick segment pumping
out NaCl. Draw the capillaries running next to the loop, and indicate with arrows the
direction of filtrate and blood movement. Show blood moving to the descending loop.
Indicate with arrows water moving out of the filtrate and entering the blood by osmosis.
Go ahead, it'll be fun!