978
UNIT 4
Maintenance of the Body
25
Homeostatic Imbalance
25.4
Chronic renal disease
, defined as a GFR of less than 60 ml/min
for at least three months, o±en develops silently and insidiously
over many years. Filtrate formation decreases gradually, nitrog-
enous wastes accumulate in the blood, and blood pH dri±s to-
ward the acidic range. Te leading cause of chronic renal disease
is diabetes mellitus (44% of new cases), with hypertension a
close second (28% of new cases). Other causes include repeated
kidney infections, physical trauma, and chemical poisoning by
heavy metals.
In
renal failure
(GFR
,
15 ml/min), filtrate formation de-
creases or stops completely. Te clinical syndrome associated
with renal failure is called
uremia
(literally “urine in the blood”)
and includes fatigue, anorexia, nausea, mental changes, and
muscle cramps.
While uremia was once attributed to accumulation of ni-
trogenous wastes (particularly urea), we now know that urea
is not especially toxic. Rather, this multiorgan failure is caused
by the interplay of multiple factors, particularly ionic and
hormonal imbalances (including anemia due to lack of eryth-
ropoietin), as well as metabolic abnormalities and accumu-
lation of various toxic molecules that interfere with normal
metabolism.
At this point, the treatment options are hemodialysis or a
kidney transplant.
Hemodialysis
uses an “artificial kidney” ap-
paratus, passing the patient’s blood through a membrane tubing
that is permeable only to selected substances. Te tubing is im-
mersed in a solution that differs slightly from normal cleansed
plasma. As blood circulates through the tubing, substances such
as nitrogenous wastes and K
1
present in the blood (but not in
the bath) diffuse out of the blood into the surrounding solution.
Meanwhile, substances to be added to the blood, mainly buff-
ers for H
1
(and glucose for malnourished patients), move from
the bathing solution into the blood. In this way, hemodialysis
retains or adds needed substances, while removing wastes and
excess ions.
Urine
Physical Characteristics
Color and Transparency
Freshly voided urine is clear and
pale to deep yellow. Its yellow color is due to
urochrome
(u
9
ro-
krōm), a pigment that results when the body destroys hemo-
globin. Te more concentrated the urine, the deeper the color.
An abnormal color (such as pink, brown, or a smoky tinge)
may result from eating certain foods (beets, rhubarb) or from
the presence of bile pigments or blood in the urine. Addition-
ally, some commonly prescribed drugs and vitamin supple-
ments alter the color of urine. Cloudy urine may indicate a
urinary tract infection.
Odor
Fresh urine is slightly aromatic, but if allowed to stand,
it develops an ammonia odor as bacteria metabolize its urea
solutes. Some drugs and vegetables alter the usual odor of urine,
as do some diseases. For example, in uncontrolled diabetes mel-
litus the urine smells fruity because of its acetone content.
Since the time of the ancient Greek Hippocrates, physicians
have examined their patients’ urine for signs of disease. How-
ever, to fully understand renal function, we need to analyze
both
blood and urine
. For example, renal function is o±en assessed by
measuring levels of
nitrogenous wastes
in blood, whereas deter-
mination of renal clearance requires that both blood and urine
be tested. Normal blood and urine values for various substances
are found in Appendix F.
Renal Clearance
Renal clearance
refers to the volume of plasma from which the
kidneys clear (completely remove) a particular substance in a
given time, usually 1 minute. Renal clearance tests are done to
determine the GFR, which allows us to detect glomerular dam-
age and follow the progress of renal disease.
Te renal clearance rate (
C
) of any substance, in ml/min, is
calculated from the equation
C
5
UV/P
where
U
5
concentration of the substance in urine (mg/ml)
V
5
flow rate of urine formation (ml/min)
P
5
concentration of the substance in plasma (mg/ml)
Because it is freely filtered and neither reabsorbed nor se-
creted by the kidneys,
inulin
(in
9
u-lin) is the standard used to
determine the GFR. Inulin is a plant polysaccharide that has a
renal clearance value equal to the GFR. When inulin is infused
such that its plasma concentration is 1 mg/ml (
P
5
1 mg/ml),
then generally
U
5
125 mg/ml, and
V
5
1 ml/min. Terefore,
its renal clearance is
C
5
(125
3
1)/1
5
125 ml/min, meaning
that in 1 minute the kidneys have cleared all the inulin present
in 125 ml of plasma.
Te clearance value tells us about the net handling of a sub-
stance by the kidneys. Tere are three possible cases:
A clearance value less than that of inulin means that the sub-
stance is reabsorbed. For example, urea has a
C
of 70 ml/min,
meaning that of the 125 ml of glomerular filtrate formed
each minute, approximately 70 ml is completely cleared of
urea, while the urea in the remaining 55 ml is recovered and
returned to the plasma. If the
C
is zero (such as for glucose
in healthy individuals), reabsorption is complete or the sub-
stance is not filtered.
If the
C
is equal to that of inulin, there is no net reabsorption
or secretion.
If the
C
is greater than that of inulin, the tubule cells are secret-
ing the substance into the filtrate. Tis is the case with most
drug metabolites. Knowing a drug’s renal clearance value is es-
sential because if it is high, the drug dosage must also be high
and administered frequently to maintain a therapeutic level.
Creatinine, which has a
C
of 140 ml/min, is freely filtered
but also secreted in small amounts. It is o±en used nevertheless
to give a “quick and dirty” estimate of GFR because it does not
need to be intravenously infused into the patient as does inulin.
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