*The
kidneys, ureters, bladder and urethra are collectively known as the urinary
system.
*
Situate in the upper part of the abdominal cavity, one on the either side
of the vertebral column.
*
12cm long by 7cm wide and dark red organs
*
characteristic bean shape, concave on its inner and convex on its outer
surface.
*
Partially embedded in fat
*
This fat helps to protect the kidneys by cushing them from impact.
I.
Basic elements
A.
The functions of kidney
1.
The primary function of kidney is to maintain constancy both of the extracellular
fluid volume and the osmolality by balancing intake and excretion of Na+,
K+ and water.
2.
Achieves constancy of blood and cellular pH by adjusting excretion of H+
and HCO3- to balance their intake and their production in metabolism
and respiration.
3.
Conserves nutrients and excretes metabolites and xenobiotics.
4.
Metabolic functions including arginine formation, gluoneogensis, peptide
hydrolysis.
5.
Site of hormone production or conversion, such as angiotensin II, erythropoietin,
postaglandins.
B.
Structure of kidney
There
are two distinct regions in a kidney:
*
The dark coloured outer zone called the renal cortex
*
The paler inner zone called renal medulla.
*The
medulla is made up of several cone shaped areas called renal pyramids.
*Urine
drains continuously from the tips of the pyramids into funnel shape spaces(
the pelvis)formed by the top of the ureter.
*The
functional units of the kidney is the nephron.
*Human
kidney contains about 1.2 million nephrons , and each is about 3 cm long.
*Each
nephron consists of a Bowman’capsule and a renal tubule and begins in the
cortex of the kidney.
*The
capsule is the blind, terminal swelling of the renal tubule and almost
surrounds a small knot of about 200 capillary loops, i.e. the glomerulus.
C.
Subunits of the nephron
1.
The renal corpuscle and blood supply
*Bowman
capsule and the glomerulus together form the Malpighian or renal corpuscle.
*The
glomerulus contains the filtering surface of the nephron.
*
The afferent arteriole brings blood to the nephron and break up into several
capillaries .
*The
capillaries are drained by an efferent arteriole which eventually joins
up with the efferent arterioles from other glomeruli to form the
renal vein .
*
However, before uniting with other arterioles, each efferent arteriole
first divides in to capillaries which form a dense network ( the peritubular
network) surrounding the nephron.
*The
filtering surface have several layers. The visceral layer of the capsule
contains the podocytes
*
Their appendages, the pedicels, interdigitate closely. The slit-like spaces
between the pedicels are covered by slit membrane with pores of 5nm diameter.
*The
other face is made up of capillary endothelium.
*A
basal membrane lies between the podocyte layer and the capillary layer.
*The
gaps in the filtration surface allow all components of blood to pass except
blood cells and solutes above a certain molecular size (MW <15,000).
2.
Proximal (convoluted) tubule:
*It
has a convoluted and a straight segment.
*
Cellular characteristic include : a brush border on the luminal surface,
elaborate inflodings of basal and lateral surface membrane, and numerous
mitochondria at the cellular side of basal and lateral surface.
3.
Loop of Henle:
*It
has a thick descending limb followed by a thin descending limb and
a thin ( in long loops only) and a thick ascending limb.
*The
long loops of Henle of the juxtamedullary nephrons dip into the inner zone
of medulla.
*
It represent about 20% of all nephrons.
*The
remaining cortical nephrons have shorter loops.
4.
Distal (convoluted) tubule
*The
distal tubule begins with straight segment (i.e. the thick ascending limb
of Henle’s loop) followed by a convoluted segment and collect to the collecting
ducts.
*No
brush border and fewer mitochondria.
5.
Collecting duct
*Several
distal tubules connect with a collecting duct
*Consisting
of anatomically and functionally distinct cortical and medullary segments
*Make
final modifications to the urine and conduct it to the pelvis for excretion
II.
Functions of renal tubule
1.
Glomerular filtration (Ultra-filtration)
*The
afferent arterioles entering the glomerulus is wider than the efferent
arteriole.
*High
blood pressure is built up inside the glomerulus.
*This
hydrostatic pressure forces water to pass through the capillary wall into
the capsular cavity.
*Although
the osmotic pressure and the hydrostatic pressure oppose the filtration,
the net filtration pressure still manage to push thing through
*The
glomerular filtrate is plasma protein and red cells free , but contains
water, glucose, amino acids, urea and mineral salts.
Glomerular
filtration rate (GFR) is the volume/time which is filtered by all glomerulus.
*
An average of 20% of the renal plasma flow is filtered at the glomerulus.
That is about 120ml/min (i.e. 180 l/day).
*However
we only produce about 1-2 l urine per day, it is obvious that most (99%)
of the filtrate is reabsorbed from the rest of the renal tubules
GFR
measurement
*For
the measurement of the GFR, an indicator that enter the tubule only by
filtration and do not undergo reabsorption, tubular excretion, or metabolism
is used.
*It
should be inert and without influence on renal function.
*Suitable
indicators are carbohydrates minnitol and inulin, which can be infused
into the blood to measure the GFR.
*Under
certain circumstance , cretinine, which is already present in the blood
may also be used.
*Since
all indicator is appear in final urine.
i.e.
the rate of filtration = rate of excretion
GFR
x Pin = Vu x Uin
The
Pin (plasma indicator conc.) ,
The
Vu (urine flow rate)
The
Uin ( urine indicator conc.)
All
the above can be obtained. So the GFR can be easily found.
Similarly
the "clearance" is the blood volume that contains the amount of substance
that is passed into urine.
i.e.
The Clearance (C) = (Udrug x Vu)/ Pdrug
*The
clearance of inulin is equal to GFR,
i.e.
the clearance ratio (C drug/ GFR) = 1 .
Because
inulin is neither reabsorbed nor secreted.
*If
the substance is removed from the tubule by reabsorption, the clearance
ratio is less than 1.0.
*If
the substance is actively secreted into the filtrate, the clearance ratio
is more than 1.
The
GFR can be altered by any changes of pressure involved in filtration.:
1.
Change in renal blood flow. e.g. renal blood flow is reduced during exercise
and hypoxia.
2.
Change in glomerular capillary blood pressure. This may due to change in
systemic arterial blood pressure or constriction of the glomerular arterioles.
3.
Change in pressure within the capsule. Maybe due to obstruction of the
ureter or oedema in the kidney
4.
Change in plasma protein concentration which alter the opposite osmotic
pressure e.g. in dehydration
5.
Renal disease. Increased permeability will allow protein to be filtered,
that reduces the osmotic pressure. If the glomeruli or tubules , the total
area of the glomerular capillary bed is reduced , so GFR will be reduced.
*
Because the GFR is subject to change in systemic blood pressure, it is
vital that renal blood flow is kept constant to ensure proper kidney function,
the kidneys are able to autoregulate its own blood supply.
2.
Tubular reabsorption
*After
filtration into the tubular fluid, many substance are reabsorbed.
*These
are chiefly electrolytes (Na+, Cl-, K+,
Ca2+, HCO3-, phosphate, etc.), amino acids, uric
acid, lactate, urea, small proteins, ascorbic acids, glucose and many more.
*Water
is passively reabsorbed according to the osmotic gradient developed.
*Na+
is reabsorbed, either an anion (e.g. Cl-, in the proximal tubule)
has to follow it, or a cation has to be secreted (H+ in the
proximal or K+ in the distal tubule).
*Glucose,
amino acids , phosphate and other substances are actively transported in
most cases. The energy is obtained by coupling with the active Na+ transport
(co-transport system).
*Certain
substance are reabsorbed by passive diffusion.
*The
permeability depends mainly on their size and their lipid solubility.
*The
nonionized form of weak electrolytes (weak acids or weak base) are more
lipid soluble. Their equilibrium between the ionic form and the non-ionic
form are depended on the pH. So by altering the pH of the tubular fluids
can enhance or reduce their reabsorption.
3.
Tubular secretion
*Many
endogenous products of metabolism , such as uric acid, glucuronides, sulphate
and exogenous substances, such as penicillin, diuretics are excreted by
active transport mechanism in different tubular regions.
*Some
substances e.g. ammonium (NH4+), H+ and hippurate,
are products of the metabolism within the tubule cells. They enter the
tubular lumen by cellular secretion.
*NH4+
diffuses passively in its non-ionic form (NH3) into the lumen,
H+ are actively secreted.
III.
Mechanism of urine concentration
*During
the time of low water intake or dehydration,
*The
kidneys must continue to eliminate wastes and excess electrolytes and conserve
water at the same time.
*This
is achieved by increasing the reabsorption of water, that cause the urine
becomes more concentrated.
1.
Proximal tubule (40-50% Na reabsorption)
*Approximately
two thirds of the tubular fluid is reabsorbed between the glomerulus and
the end of the proximal tubule.
*Reabsorption
of Na+ is the primary driving event in water reabsorption.
It
establishes a small concentration gradient which allow the water to diffuse
back to the surrounding capillaries.
*Oncotic
pressure in the capillaries( due to the concentrated plasma protein) provides
an additional force of movement.
2.
Loop of Henle (30-40% Na)
*The
thick ascending limb of the loop of Henle actively transport NaCl into
the medullary ECF.
*Since
cells of the thick limb are relatively impermeable to water, the fluid
that remains in the tubule is hyposmolal (less concentrated than body fluid).
*The
reabsorbed NaCl establishes an osmotic gradient that is greater towards
the papillary tip.
*Urea
and other solutes also contribute this gradient In the thin descending
limb, the tubular fluid equilibrates with the ECF, net efflux of water
occurs.
*Due
to the close proximity of the loop of Henle and the vasa recta capillaries.
The water is mainly returned in the vasa recta.
Countercurrent
system
*The
loop of Henle is increasing the solute concentration of the kidney tissue
by creating a gradient of osmolarity from the cortex to the medulla.
*Its
characteristic U shape provides a countercurrent system that establish
a continuous concentration difference.
*Without
this gradient, water could not be reabsorbed in the loop or the collecting
ducts, nor ion diffusion occur from the thin ascending limb.
*Countercurrent
multiplication system in the loop does not itself concentrate the urine
but rather creates conditions in the medulla under which a concentrated
urine can be formed.
3.
Distal tubule (10% Na)
*Distal
tubule receives slightly hypo-osmotic urine from the loop of Henle.
*The
volume of the filtrate has been greatly reduced.
*In
this region, active transport if Na+ occurs, followed passively by Cl-
and water follows by osmosis.
4.
The collecting duct (2-4%)
*The
collecting duct is the place that final adjust of urinary volume and concentration
takes place.
*The
water permeability can be modified by the hormone ADH (anti-diuretic hormone)
ADH
*When
the water content of the blood falls, as in dehydration, the interstitial
fluid osmotic pressure rises.
*The
osmoreceptors in the hypothalamus trigger the release of ADH from the posterior
pituitary into the blood stream.
*The
ADH is then increases the permeability of the collecting ducts
*Water
diffuses out of the medullary collecting ducts into the hyperosmolal environment
in the medullary ECF, and hyper-osmotic urine is produced, the concentration
limit of the urine is set by the medullary osmolality.
*As
the sufficient water is reabsorbed, ADH secretion decrease ( a negative
feedback mechanism).
IV.
Hormonal control of sodium reabsorption
*Aldosterone
is produced by the adrenal cortex
*It
stimulates distal tubular reabsorption of sodium, and in its absence (as
in Addison disease) as much as 25 g of salt per day may be excreted.
Aldosterone
*
Aldosterone secretion is stimulated by the angiotensin II which is controlled
by reflexes initiated by the juxtaglomerular apparatus of the kidneys.
*A
reduction in sodium concentration within the distal tubule wall stimulate
the secretion of renin by the juxtaglomerular cells, which are able to
detect the Na+ concentration alternation within the distal tubule.
Renin-Angiotensin
system
*
Decreased renal blood flow stimulates the release of renin from kidney
*Renin
act on the renin substrate, the angiotensinogen (from liver), and forming
angiotensin I
*The
angiotensin I is further converted to the highly active angiotensin
II.
*The
converting enzyme is a peptidase which situates in the lung, the kidney
and some other tissues.
Virtual
University of Pharmaceutical Science 