Renal System - General Notes
The
main functions of the kidneys:
v
Regulation of water and inorganic ion balance
v
Excretion of metabolic waste products
v
Excretion of foreign substances
v
Secretion of hormones
Body
Fluid Compartments
The
body can be split up into two main compartments. Intracellular compartment is
the fluid present within each individual cells, and extracellular compartment is
the fluid outside the cell. The body is made up of about 40L of fluid out of
which 25 L is made up by the intracellular compartment. The extra-cellular
compartment can be split into two subdivisions and these are:
The
fluid present within interstitial fluid and the fluid present within plasma, the
fluid component of blood. This accounts for about 12L and 3 L of the remaining
fluid respectively.
The
kidneys are located between T12-L3, just above the waist region. The right
kidney is lower than the left due to the diaghragm extending superiorly across
it. The lateral surface is convex and the medial surface is concave. The renal
hilus is where the lymphatics, blood vessels and nerves enter the kidney.
The internal structure of the kidney is different. It contains a granular outer margin called the renal cortex, and this is where all of the renal corpuscles are found. The inner area is called the renal pelvis, which is a tube continuous with the ureter. The middle region is called the medulla and it contains cone shaped masses of tissue called renal pyramids.
Note:
The anatomy of the kidney will be dealt with in great detail in Gross Anatomy.
It is not absolutely necessary to know the complete details of this, but knowing
it may help you correlate the anatomical features to its histological features.
Integrating histology with human biology will also help your understanding, and
in my opinion is worthwhile in understanding the renal system.
The
nephron is the functional unit of the kidney. It is made of the renal corpuscle,
the proximal convoluted tubule and the distal convoluted tubule, and in betweem
the loop of Henle.
The
renal corpuscle consists of the afferent and efferent arteriole going into a
tuft of capillaries called the glomerulus. The end of the nephron is cup shaped
and enclosed these capillaries, and in between you have the bowman’s space.
The complete capsule is called the bowman’s capsule. The total structure is
called the renal corpuscle. The nephron then goes on to become the highly
convoluted proximal tubule and takes a hair pain bend to become the distal
convoluted tubule.
There
are a number of collecting ducts which collect the urine from many nephrons and
relays this to the papillary ducts, which in turn relay it to minor and major
calyces. These drain into the renal pelvis to be taken away by the ureter for
excretion.
The
epithelium of the nephron changes as we move through it. The proximal convoluted
tubule is made up of a simple cuboidal epithelium with microvilli present atop
the cells. This helps them in absorption of most of the fluids and ions back
into the blood stream. The thin descending loops of henle are made of a simple
squamous epithelium and this allows easy diffusion of water across its barriers.
The thick ascending loop of henle is made of simple cuboidal epithelium and this
continues on to the distal convoluted and collecting ducts.
Urine
formation involves three main processes: glomerular filtration, tubular
reabsorption, tubular secretion.
The
first of these process involves glomerular filtration, where the blood rushes
into the glomerular capillaries allowing for the easy passage of ions and water
into the bowmans space to be taken away by the tubules of the nephron.
This
involves passage across the filtration membrane. The filtration membrane is made
up of three components. The fenestrated capillary endothelium, the visceral
layer of the glomerular capsule (made up by pododcytes) and the fused basal
laminas of the podocytes and endothelial cells. There are small filtration slits
which extend between the processors of the podocytes.
The
red blood cells are stopped from passing by the membrane existing across the
capillary endothelium. The plasma proteins are stopped from entering the capsule
by the fused basal laminas. In cases where plasma proteins pass the laminas,
then they are barred from entering by the small filtration slits existing
between the podocyte processors.
Capillary
hydrostatic pressure is the force tending to push fluid out of the blood. This
is due to the high capillary blood pressure at the glomerular capillaries.
Plasma oncotic pressure is directed related to the concentration of plasma
proteins and the force tending to push fluid back into the capillary. As entry
of plasma proteins is barred by the filtration membrane, there is always an
imbalance between the capillary hydrostatic pressure and plasma oncotic
pressure. This is known as the net filtration pressure.
The
Glomerular filtration rate is defined as the rate of filtrate formation per
minute by the kidney and is determined by three factors; the SA of the
filtration area, the permeability of the filtration membrane and the net
filtration pressure.
Increased
surface area for filtration to occur means that there is increased rate of
filtration and therefore more filtrate is formed per minute by the kidney.
Increased permeability of the filtration membrane means that more substances
(i.e.: water and ions) pass through it in a given period of time, and therefore
the net filtrate formed in that same
time is greater. The net filtration pressure is defined as the pressure
by the capillary hydrostatic pressure and the plasma oncotic pressure. Thus an
increased net filtration pressure means more force exists to push fluid out of
the capillary, therefore more fluid passes and therefore more filtrate is
formed.
Measure
Glomerular filtration rate clearance is a way of testing for renal failure. This
is the volume of plasma from which a particular substance is fully excreted by
the kidney. This is measured by: RC = UV/P where U – concentration of
substance in blood, V – flow rate of urine formation, P – concentration of
substance in plasma.
There
are three main mechanisms of control of the glomerular filtration rate. These
are autoregulatory mechanism, neural control, and hormonal control. The reason
these controls are required is because of extreme stresses put on the body at
certain circumstances, therefore the blood supply to the kidneys must be
compromised.
Autoregulatory
mechanism is an intrinsic control mechanism in which the kidney itself is
involved in the control of the capillary hydrostatic pressure and therefore as a
result control the glomerular filtration rate. This is the first mode of
mechanism used to control GFR. There are two types of autoregulation. One is
myogenic regulation and the other is tubuloglomerular mechanism. Myogenic
regulation involves the reflex constriction of the arterioles, mainly afferent,
in response to a very high GFR or flow rate of filtrate. This means that the
smooth muscle around the arterioles contract to constrict the blood vessel,
therefore less blood enters the glomerular capillaries and hence less capillary
hydrostatic pressure, therefore lowering the GFR. The tubuloglomerular mechanism
involves the macula densa cells of the juxtaglomerular apparatus situated on the
walls of the distal convoluted tubules. These cells monitor the filtrate
concentration of particular ions, for example sodium. When these ions are too
high in concentration they cause vasconstriction of the afferent arterioles and
therefore reduce GFR. When the filtrate flow rate is low, then they vasodilate
the arterioles which results in an increase in GFR.
Neural
mechanisms are also involved in controlling the GFR. This involves the
sympathetic stimulation of the smooth muscle cells surrounding the arterial
vessels. This is normally involved in events where other areas of the body (such
as heart) require an increased supply of blood. For example: in the event of
severe hyptension, where the arterial blood pressure within the systemic
circulation is decreased below normal levels – the sympathetic nerve fibres
innervating the smooth muscle increases in activity causing vasoconstriction of
the arterioles, lowering amount of blood entry into the glomerular capillaries.
Also, the adrenal medulla increases release of adrenaline which binds to alpha
adrenergic receptors on the smooth muscle cells, causing addition
vasoconstriction. This also trips the renin-angiotensin system of the kidney by
stimulating the macula densa cells of the juxtaglomerular apparatus.
The
renin angiotensin system is the hormonal mechanism in which the GFR is
controlled. This involves the release of renin the juxtaglomerular cells
situated on the walls of the distal convoluted tubules of the juxtaglomerular
apparatus, and renin promotes the conversion of angioteninogen to angiotensin I.
This in turn is converted to angiotensin II by the ACE enzyme. Angiotensin II is
a potent vasoconstrictor and also stimulates release of aldersteron by the
adrenal cortex. This stimulates increased reabsorption of sodium ions and water
follows passively, therefore increasing blood pressure. The factors that
determine this are: the level of stretch of the juxtaglomerular cells within the
juxtaglomerular apparatus, the level of sympathetic activity and the level of
activation of the macula densa cells.
Tubular
reabsorption involves two pathways. One is through the tubular cell and the
other is through the gaps between the tubular cells. These are transcellular and
paracellular pathways, respectively. Paracellular pathways is only efficient
where the tight junctions between tubular cells are not effective, and this is
only in the proximal tubules of the nephron.
The
transcellular pathways involves movement of substance through the luminal
membrane, cell cytoplasm, cell basolateral membrane, interstitial fluid,
capillary basement membrane, capillary endothelium and into the peritubular
capillaries. The para cellular pathway involves the movement of substance
through the leaky tight junctions of the tubular cells. This pathways involves
movement of substance through the tight junctions, interstitial fluid, capillary
basement membrane, capillary endothelium and into the peritubular capillaries.
There
are two mechanisms of reabsorption in the tubules of the nephron. Most of the
reabsorption occurs in the proximal convoluted tubule, and out of 100% à
99% is reabsorbed back into the capillaries and only 1% is excreted as urine
which accounts for about 1.5L per day.
Tubular
reabsorption can be an active or a passive process. Active process require ATP
in at least one of the processes of absorption, whereas passive requires no ATP.
Sodium
Reabsorption (Primary Active Transport)
Sodium
reabsorption is an active transport mechanism and it is vital as most of ion
concentration in the filtrate is made up of sodium ions. It also is responsible
for the passive following of water, and other nutrients and also permits
excretion of potassium ions and hydrogen ions.
Sodium
is transported out of the cell by the sodium potassium ATPase pump. At the same
time potassium ions are pumped into the cell, but these ions diffuse outside the
cell immediately through leakage channels present. The excretion of sodium to
the extracellular environment, means the concentration of sodium inside the
cells is low. Also, the net movement of sodium leaves a relative negative charge
on the interior of the cell. This sets up a strong electrochemical gradient.
Thus sodium moves into the cell by diffusion through the ion channels in the
luminal membrane. Out of the three tubules types: approximately 65-70% of the
sodium present in the filtrate is reabsorbed in the proximal tubules, about
20-25% in the loop of henle and about 10% in the distal convoluted tubule. These
figures are according to Marieb, 4th edition.
Major
Points: Sodium enters the cell using a membrane transporter >
brings in glucose with it > against a concentration gradient > only occurs
in the proximal tubules > when glucose load in filtrate is too high > goes
above the transport maximum for the Na/Glucose transporters > therefore
glucose appears in urine
Water
reabsorption (Na water coupling à
Passive Transport)
Water
is reabsorbed into the peritubular capillaries by osmosis, a passive process.
When sodium moves out into the peritubular capillaries, the osmotic pressure
within the cytosol of the cell and also the peritubular capillaries increases.
Therefore water follows passively, by transcellular or paracellular pathway. The
movement of water means the concentration of solutes in the filtrate has
increased, therefore they also following.
The
movement of sodium sets up a concentration gradient for water, and also other
solutes therefore promoting movement of other solutes into the peritubular
capillaries. Water
is absorbed about 65-70% in PCT, 20-25% in loop of henle and 20% in DCT.
The
transport of chloride is also linked to the movement of sodium from the tubule
lumen and into the capillaries. This movement initiates a postive charge within
the interstial fluid between the capillary endothelium and the basolateral
membrane of the tubular cells. Thus, as chloride is negatively charged, it
follows to neutralise this positive. The further movement of sodium into the
peritubular capillaries involves the transport of chloride by diffusion or bulk
flow.
50%
of the total chloride is reclaimed in PCT, 35% in loop of henle.
Acetylcholine
– organic cations, Prostaglandins – organic anions.
Roles
of different parts of the nephron
The
proximal tubule massively reabsorbs most of the filtrate fluid in a unselective
way. This means, sodium, water, chloride and urea are all reabsorbed in this
part of the nephron. In the loop of henle, water is reabsorbed, sodium is
reabsorbed and chloride ions passively follow. The function of the loop of henle
is mainly to concentrate the urine by allowing water movement out of it and into
the peritubular capillaries. The distal tubules and collecting ducts contains
cells that are responsible for fine tuning the composition of urine, the
relative concentrations of solutes, urea and nutrients. This is done by the
macular densa cells and the granular cells of the juxtaglomerular apparatus.
These cells are located within the walls of the endothelium lining of the
peritubular capillaries and also the walls of the tubular epithelium.
Major
Points: Descending limb of loop of henle, permeable to water but not
to salts > as a result water moves out into the medullary interstitial fluid >
the osmolality increases in the loop of henle tubule >
at the turnaround >
the most concentration present > then ascending loop of henle >
impermeable to water > permeable to salts > salts move out > water
stays > osmolality of medullary interstitial fluid increases > dilute
urine present.
Major
Points (after loop of henle): Urea is
impermeable in tubules > in collecting ducts it is permeable >
urea leaves and enters medullary interstitial fluid > therefore increase in
osmolality > In a normal hydrated person > urine flows into the collecting
ducts and distal conv. Tubules without much change > in a dehydrated person
> ADH is produced by the hypothalamus > released by posterior pituatary
gland > increases no. of water filled channels in principal cells in the
collecting ducts > as a result > osmolality of filtrate is high > urine
is concentrated.
Note
that the loop of henle is responsible for the production of a steep
concentration gradient between the tubule lumen and the medullary interstitial
fluid. It is not responsible for concentrating the urine. Urine is only
concentrated by ADH when person is dehydrated.
This
is a thin slender tube which runs from the renal pelvis to the bladder. It
enters the bladder posteriorly after turning medially and running obliquely.
This arrangement prevents the backflow of urine when the bladder fills up. The
ureter walls are made up of mucosa (transitional epithelium, lamina propria,
muscularis mucosa), muscularis, and adventitia. It moves urine along its length
and into the bladder by peristaltic contractions contributed by the tunica
muscularis (two layers, inner circular and outer longitudinal).
The
bladder is composed of three layers. The mucosa (transitional epithelium, lamina
propria, and muscularis mucosa) + detrusor muscle (inner and outerlongitudinal
layers and middle circular layer) + fibrous adventitia providing structural
integrity. The trigone is clinically relevant (the triangular area where the
bladder drains into the urethra and ureter into the bladder) because most
infections that occur in the urinary system, occur here.
Muscular
tube which conveys urine from the bladder to the outside world. There are two
junctions. Bladder-Urethra Junction à
Internal urethra junction à
which
is largely smooth muscle à
caused by thickening of the smooth muscle layer à
external urethral spinchter à
Made of skeletal muscle and is under voluntary control.
The
act of emptying the bladder. When the bladder becomes distended, stretch
receptors located within the wall are activated and send afferent impulses to
the spinal cord which brings about a visceral reflex arc. Efferent signals are
then transmitted to the destrusor muscle governing the internal urethra
spinchter, this contracts relaxing the Sphincter allowing passage of urine into
the urethra. Then the external sphincter is under voluntary control, therefore
we can open or close this at our control depending on the appropriate situation.
The
fluids of the body are stored in two main compartments. Intracellular and
Extracellular Compartments. The intracellular component refers to the fluid
stored within the tiny individual units called cells. This normally accounts for
about 25L of the total 40L of fluid stored in the body. The extracellular
compartment is made of two sub compartments. These are the plasma which is the
fluid portion of blood in blood vessels and the interstitial fluid which is the
fluid present between the tissue cells. This accounts for about 3 and 12 L of
the remaining portion of body fluid volume, respectively.
Sodium ions are in abundance in the extracellular compartment. Potassium ions are in abundance within the cell. Thus an increase in sodium uptake in the body will automatically reside in the extracellular compartment of the body fluids. This means that the osmolality of this compartment increases and therefore, it has more particles dissolved per 1000g of water. Hence, water will diffuse into the extracellular comparment following its osmotic gradient, and this is a passive process known as osmosis. Thus the total volume of the extracellular compartment is increased as a result.
Possible
Question: Discuss the ways in which water balance is achieved. Include the
regulation of water uptake, output.
Water
balance is achieved by matching the amount of water intake with the amount of
water output. Water intake is mainly by fluids and solid food injected, with
about 10% coming from metabolism. Metabolism produces metabolic water. Water
output occurs in several ways, vapour during inspiration and expiration, urine,
feces, perspiration and diffusion through skin. But the regulation of water is
done by the kidney. This is done by regulating the concentration of the urine,
due to the maintenance of the medullary osmotic gradient.
Regulation
of water uptake is done by the thirst center of the hypothalamus. When body
water levels go down, it creates a dry mouth and this initiates the thirst
center of the hypothalamus. The causation of the dry mouth is mainly due the
increase in plasma oncotic pressure and therefore the force which drives fluid
into the tissues is reduced by this rise. As the salivary glands receive their
water from the blood, the production of saliva is decreased due a decrease in
supply of water from the water. The hypothalamic thirst center is stimulated
when its osmoreceptors lose water by osmosis, and therefore they stimulate
uptake of water by making us drink water.
The amount of sodium present within the extracellular compartment is directly related to the amount of fluid present in the extracellular compartment. Thus when a person ingests one litre of water into the body, the osmolality of the extracellular compartment is decreased and as a result the inhibition to secrete ADH by the hypothalamus and release by the posterior pituitary is evident. Therefore the water channels of the collecting duct cells is not opened, therefore no water is reabsorbed and the urine is more dilute.