kidney 2
By
Mona Abu Bakr El-Hussiny
Assistant Lecturer of Clinical Pathology, Clinical
Pathology Department,
Faculty of Medicine –Mansoura University
Renal function
excretory regulatory endocrine
THE FORMATION OF URINE
FIGURATION, REABSORPTION, AND
SECRETION
Every one of us depends on the process of urination for
the removal of certain waste products in the body. The
production of urine is vital to the health of the body.
Urine is composed of water, certain electrolytes, and
various waste products that are filtered out of the
blood system.
Remember, as the blood flows through the body, wastes
resulting from the metabolism of foodstuffs in the
body cells are deposited into the bloodstream, and
this waste must be disposed of in some way. A major
part of this "cleaning" of the blood takes place in the
kidneys and, in particular, in the nephrons, where
the blood is filtered to produce the urine. Both
kidneys in the body carry out this essential blood
cleansing function. Normally, about 20% of the total
blood pumped by the heart each minute will enter
the kidneys to undergo filtration. This is called the
filtration fraction.
Filtration
Urine formation begins with the process of
which goes on continually in the renal
corpuscles. As blood courses through the
glomeruli, much of its fluid, containing both
useful chemicals and dissolved waste
materials, soaks out of the blood through the
membranes (by osmosis and diffusion) where
it is filtered and then flows into the Bowman's
capsule.
This process is called glomerular filtration.
The water, waste products, salt, glucose, and
other chemicals that have been filtered out
of the blood are known collectively as
glomerular filtrate. The glomerular filtrate
consists primarily of water, excess salts
(primarily Na +and K ,)+glucose, and a
waste product of the body called urea.
Urea is formed in the body to eliminate the
very toxic ammonia products that are
formed in the liver from amino acids. Since
humans cannot excrete ammonia, it is
converted to the less dangerous urea and
then filtered out of the blood .
Urea is the most abundant of the waste
products that must be excreted by the
kidneys. The total rate of glomerular
filtration( glomerular filtration rate or
GFR) for the whole body (i.e., for all of the
nephrons in both kidneys) is normally about
125 ml per minute. That is, about 125 ml of
water and dissolved substances are filtered
out of the blood per minute
glomerular filtration rate=glumerular pressure –
( osmotic pressure + Bomans capsular pressure).
The first process in urine formation, returns to
the blood by the second process - reabsorption.
Reabsorption
Reabsorption, by definition, is the movement of
substances out of the renal tubules back into
the blood capillaries located around the
tubules. Substances reabsorbed are water,
glucose and other nutrients, and sodium (Na+)
and other ions. Reabsorption begins in the
proximal convoluted tubules and continues in
the loop of Henle, distal convoluted tubules,
and collecting tubules.
Large amounts of water - more than 178 liters per
day - are reabsorbed back into the bloodstream
from the proximal tubules because the physical
forces acting on the water in these tubules
actually push most of the water back into the
blood capillaries. In other words, about 99% of
the 180 liters of water that leave the blood each
day by glomerular filtration returns to the blood
from the proximal tubule through the process of
passive reabsorption.
The nutrient glucose (blood sugar) is entirely
reabsorbed back into the blood from the proximal
tubules. In fact, it is actively transported out of
the tubules and into the peritubular capillary
blood. None of this valuable nutrient is wasted by
being lost in the urine. However, even when the
kidneys are operating at peak efficiency, the
nephrons can reabsorb only so much sugar and
water
Their limitations are dramatically illustrated in
cases of diabetes mellitus, a disease which
causes the amount of sugar in the blood to rise
far above normal. As already mentioned, in
ordinary cases all the glucose that seeps out
through the glomeruli into the tubules is
reabsorbed into the blood .
But if too much is present, the tubules reach the
limit of their ability to pass the sugar back into
the bloodstream, and the tubules retain some of
it. It is then carried along in the urine, often
providing a doctor with her first clue that a
patient has diabetes mellitus.
Sodium ions (Na )+and other ions are only
partially reabsorbed from the renal tubules
back into the blood. For the most part,
however, sodium ions are actively
transported back into blood from the tubular
fluid. The amount of sodium reabsorbed varies
from time to time; it depends largely on how
much salt we take in the foods that we eat .
As a person increases the amount of salt taken into the
body, that person's kidneys decrease the amount of
sodium reabsorption back into the blood. That is,
more sodium is retained in the tubules. Therefore, the
amount of salt excreted in the urine increases. The
less the salt intake, the greater the amount of sodium
reabsorbed back into the blood, and the amount of
salt excreted in the urine decreases .
Secretion
Secretion is the process by which substances
move into the distal and collecting tubules from
blood in the capillaries around these tubules. In
this respect, secretion is reabsorption in reverse.
Whereas reabsorption moves substances out of
the tubules and into the blood, secretion moves
substances out of the blood and into the tubules
where they mix with the water and other wastes
and are converted into urine
These substances are secreted through either an
active transport mechanism or as a result of
diffusion across the membrane. Substances
secreted are hydrogen ions (H+), potassium
ions (K+), ammonia (NH3), and certain drugs.
Kidney tubule secretion plays a crucial role in
maintaining the body's acid-base balance,
another example of an important body function
that the kidney participates in.
Extracellular homeostasis
The kidney is responsible for maintaining a
balance of several substances:
Substance Description Proximal
tubule
Glucose
If glucose is not reabsorption
reabsorbed by
(almost
the kidney, it
100%) via
appears in the
sodiumurine, in a
glucose
condition
transport
known as
proteins
glucosuria. This apical) and(
is associated
GLUT
diabetes with )basolateral(
mellitus
.
Loop of
Henle
Distal
tubule
Collecting
duct
,Oligopeptides
proteins, and
amino acids
All are
reabsorption
reabsorbe
d nearly
completely
Urea
Regulatio
n of
osmolality.
Varies
ADH with
reabsorption secretion
(50%) via
passive
transport
reabsorption
in
medullary
collecting
ducts
Sodium
Na- Uses
H antiport,
Na
reabsorption
reabsorption reabsorptio
reabsorption
(25%, thick
,(5%
,n (5%
glucose
symport ,
sodium ion
channels
(minor )
Chloride
65 %
isosmotic
Usually
reabsorptio
follows
n
sodium.
Active
(transcellular)
and passive
(paracellular)
ascending ,
Na-K-2Cl
symporter)
sodiumchloride
symporter)
reabsorptio
n (thin
ascending,
thick
ascending ,
Na-K-2Cl
symporter)
reabsorptio
n( sodiumchloride
symporter)
principal
cells),
stimulated
by
aldosterone
Water
Bicarbonate
Uses
aquaporin
water
channels.
See also
diuretic
absorbed
osmotically
along with
solutes
reabsorptio
n
(descending
)
reabsorption
(regulated by
ADH, via
arginine
vasopressin
receptor 2)
Helps
maintain
acid-base
balance.
reabsorptio
n (80-90%)
reabsorptio
n (thick
ascending)
reabsorption
(intercalated
cells, via band
3 and pendrin)
Potassium
Varies upon reabsorptio
dietary
n (65%)
needs
reabsorptio
n (20%,
thick
ascending,
Na-K-2Cl
symporter)
Calcium
Uses
calcium
ATPase,
sodiumcalcium
exchanger
reabsorptio
n (thick
ascending)
via passive
transport
reabsorptio
n
secretion
(common,
via
Na+/K+ATPase,
increased
by
aldosterone
), or
reabsorptio
n (rare,
hydrogen
potassium
ATPase
Magnesium Calcium
reabsorptio
and
n
magnesium
compete,
and an
excess of
one can
lead to
excretion of
the other.
Phosphate
Excreted as
titratable
acid
reabsorptio
n (85%) via
sodium/pho
sphate
cotransport
er Inhibited
by
parathyroid
hormone
reabsorptio
n (thick
ascending)
reabsorptio
n
Acid base homeostasis:
The body is very sensitive to its pH level.
Outside the range of pH that is compatible
with life, proteins are denatured and digested,
enzymes lose their ability to function, and the
body is unable to sustain itself. The kidneys
maintain acid-base homeostasis by regulating
the pH of the blood plasma. Gains and losses
of acid and base must be balanced. Acids are
divided into "volatile acids" and "nonvolatile
acids".
About 90% of filtered bicarbonate is reabsorbed in PCT
with the remaindered reabsorbed in the DCT and
CD. In the PCT this is a consequence of H ion
secretion and the action of the enzyme carbonic
anhydrase. In the DCT , after the bicarbonate has
been predominantly removed, secreted H ions are
taken up by other buffers as phosphate . in most part
of nephrone, predominantly in the PCT, ammonium
ions are generated as the result of deammination of
glutamine. The ammonium ions is secreted into the
tubular lumin, generating intracellular bicarbonate.
Water homeostasis:
Water homeostasis is determined by :
water intake
extrarenal water loss.
Solute load
Kidney ability to produce concentrated or
diluted urine
The minimum urine volume is determined by
solute load to be excreted and may be as low
as 400 ml/ d.
The maximum urine volume is determined by
water load to be excreted and may be as mnch
as 20-25 L/ d.
Osmolal clearance ( C osm) represent
volume of urine that would be required
for isoosmolal clearance of solute load.
Free water clearance
Negative free water
clearance
Difference between actual
urine flow rate and flow
rate calculated for
isosmotic excretion .
Measure diluting ability
In excess that required for
isoosmolal urine
C H2O= V-C osmo
Measure concentrating
ability
Water reabsorbed from
tubular fluid during
production of concetrated
hypertonic urine
C H2O= C osmo - V
Two main process are involved in in water
reabsorption
 Isosmotic reabsorption of water from PCT:
About 80% returned to the body by PCT
Active solute reabsorption from the filterate is
accompanied by passive reabsorption of an
osmotically equivelant amount of water
 Differential reabsorption of water and solute
from the loop of Henle, DCT, CD: two
mechanism are involved
Countercurrent multiplication
Countercurrent
exchange
Active process
Passive process
In loop of Henle
In DCT and CD
In absence of ADH
In presence of ADH
Lead to production of diluted urine In abscence of ADH the
(low osmolarity) and increase
collecting duct impermeable
plasma osmolality.( in loop of Henle
to water
reab of Na & Cl without water).
Produce conc.urine and
plasma is diluted
Endocrine function:
Hormones produced by the
kidne
Renine – erythropoietinprostaglandins- kinin-vit Dnatriuretic peptides
Aldosterone- PTH- ADHcalcitonin- natriuretic Hthyroid H- glucocorticoidsomatomedin.
Hormones catabolised by the PTH- calcitonin- insulinsomatomedin- GIT hormoneskidney
vasopressin- hypothamic RHprolactin- angiotensin II.
Hormones that control
kidney function
Aldosterone
Aldosterone is a steroid hormone (mineralocorticoid
family) produced by the outer-section (zona
glomerulosa) of the adrenal cortex in the adrenal gland,
and acts on the distal tubules and collecting ducts of the
kidney to cause the conservation of sodium, secretion of
potassium, increased water retention, and increased
blood pressure. Aldosterone is part of the reninangiotensin system.
Its activity is reduced in Addison's disease and increased
in Conn syndrome.
vasopressin
Arginine vasopressin (AVP), also known as
vasopressin, argipressin or antidiuretic
hormone (ADH), is a hormone found in most
mammals, including humans.[1] Vasopressin is
a peptide hormone. It is derived from a
preprohormone precursor that is synthesized in
the hypothalamus and stored in vesicles at the
posterior pituitary.
vasopressin
Arginine vasopressin (AVP), also known as
vasopressin, argipressin or antidiuretic
hormone (ADH), is a hormone found in most
mammals, including humans.[1] Vasopressin is
a peptide hormone. It is derived from a
preprohormone precursor that is synthesized in
the hypothalamus and stored in vesicles at the
posterior pituitary.
One of the most important roles of AVP is to
regulate the body's retention of water; it is
released when the body is dehydrated and
causes the kidneys to conserve water, thus
concentrating the urine, and reducing urine
volume. In high concentrations, it also raises
blood pressure by inducing moderate
vasoconstriction.
AVP increases the permeability to water of the
distal convoluted tubules and collecting
tubules in the nephrons of kidneys and thus
allows water reabsorption and excretion of a
smaller volume of concentrated urine antidiuresis. This occurs through insertion of
additional water channels (Aquaporin-2s) into
the apical membrane of the tubules/collecting
duct epithelial cells. The aquaporins allow
water to pass out of the nephron (at the distal
convoluted tubules and the conducting tubules)
and into the cells, increasing the amount of
water re-absorbed from the filtrate
Erythropoietin or EPO
Is a glycoprotein hormone that controls
erythropoiesis, or red blood cell production. It is a
cytokine for erythrocyte (red blood cell)
precursors in the bone marrow. It is produced by
the kidney, and is the hormone that regulates red
blood cell production. It also has other known
biological functions. For example, erythropoietin
plays an important role in the brain's response to
neuronal injury. EPO is also involved in the
wound healing process.
An intermediate is created by phospholipase-A2,
then passed into one of either the
cyclooxygenase pathway or the lipoxygenase
pathway to form either prostaglandin and
thromboxane or leukotriene. The
cyclooxygenase pathway produces
thromboxane, prostacyclin and prostaglandin
D, E and F. The lipoxygenase pathway is
active in leukocytes and in macrophages and
synthesizes leukotrienes.
Types
Following is a comparison of the prostaglandin
types Prostaglandin I2 (PGI2), Prostaglandin
E2 (PGE2) and Prostaglandin F2α (PGF2α).
Type
Receptor
Function
IP
vasodilation
inhibit platelet aggregation
bronchodilatation
EP1
bronchoconstriction
GI tract smooth muscle contraction
EP2
bronchodilatation
GI tract smooth muscle relaxation
vasodilatation
EP3
↓ gastric acid secretion
↑ gastric mucus secretion
uterus contraction (when pregnant)
GI tract smooth muscle contraction
lipolysis inhibition
PGI2
PGE2
↑ autonomic neurotransmitters [6]
Unspecified hyperalgesia[6]
pyrogenic
PGF2α FP
uterus contraction
bronchoconstriction
Vitamin D
Vitamin D3 has several forms:
Cholecalciferol, (which is an inactive,
unhydroxylated form of vitamin D3)
Calcidiol (also called 25-hydroxyvitamin D3),
which is the form measured in the blood to
assess vitamin D status
Calcitriol (also called 1,25-dihydroxyvitamin
D3), which is the active form of D3.
is a form of Vitamin D3 with three alcohol
groups. It increases gastrointestinal Calcium
absorption, stimulates osteoclastic Calcium
resorption from bone, facilitates the effect
Parathyroid Hormone (PTH) has on bone
resorption, and increases renal tubular
absorption of Calcium. Production of
Calcitriol by the cells of the Proximal Tubule
of the nephron in the kidney is stimulated by
hypocalcemia and hypophospatemia.
Metabolism
7-Dehydrocholesterol is the precursor of vitamin
D3 and forms cholecalciferol only after being
exposed to solar UV radiation.
Cholecalciferol is then hydroxylated in the liver
to become calcidiol (25-hydroxyvitamin D3).
Next, calcidiol is again hydroxylated, this time in
the kidney, and becomes calcitriol (1,25dihydroxyvitamin D3). Calcitriol is the most
active hormone form of vitamin D3.
Laboratory tests:
Glomerular function tests:
clearance
Creatinine clearance test.
This test evaluates how efficiently the kidneys clear a
substance called creatinine from the blood. Creatinine, a
waste product of muscle energy metabolism, is produced at
a constant rate that is proportional to the individual's muscle
mass. Because the body does not recycle it, all creatinine
filtered by the kidneys in a given amount of time is excreted
in the urine, making creatinine clearance a very specific
measurement of kidney function. The test is performed on a
timed urine specimen—a cumulative sample collected over
a two to 24-hour period. Determination of the blood
creatinine level is also required to calculate the urine
clearance.
Calculation of CCr
The urinary flow rate is still calculated per minute,
hence
To allow comparison of results between
people of different sizes, the CCr is often
corrected for the body surface area (BSA)
and expressed compared to the average
sized man as mL/min/1.73 m2. While most
adults have a BSA that approaches 1.7 (1.61.9), extremely obese or slim patients
should have their CCr corrected for their
actual BSA