Introduction to Clinical Medicine - Nephrology
I. David Weiner, M.D.
Professor of Medicine and Physiology
University of Florida College of Medicine and NF/SGVHS
Please e-mail me, at weineid@ufl.edu,
with your questions. I'll post the question and my answer, with your
permission, here for others to see.
Questions and Answers from 2008
Questions and answers are posted in reverse chronological order
so that the most recent questions and answers are at the top. I hope this
makes it easier for you to find answers to your questions!
March 27, 2008
Hi Dr. Weiner,
I was a little confused about a statement in the potassium
disorders lecture. It says that "hypokalemia causes hypertension, this is due,
at least in part, to sodium retention and ECV expansion". Does this mean that
hypokalemia is causing aldo secretion? I thought it was the other way around (ie
sodium retention causes hypokalemia due to the potassium wasting action of aldo
at the collecting duct). Thanks for your help!
- Hypokalemia is, in fact, an important and easily treatable cause of
hypertension. The mechanisms are multifactorial and complex.
The first component appears to be that hypokalemia stimulates H-K-ATPase
expression in the collecting duct. Sodium is able to substitute for
potassium at potassium-binding site of H-K-ATPase, resulting in increased
sodium absorption, which leads to increased intravascular volume and
worsening of the hypertension.
Second, hypokalemia increases vascular reactivity, probably through
increased oxygen free radical generation. This both directly increases blood
pressure and indirectly, by decreasing renal perfusion pressure by causing
vasoconstriction of small vessels inside the kidney, makes the kidney think
the blood pressure is actually decreased, which further stimulates renal
sodium reabsorption, thereby increasing intravascular volume even more.
Finally, there are number of other mediators that are increased in
response to hypokalemia but also contribute to worsening hypertension. Thus,
hypokalemia through wide variety of mechanisms increases blood pressure.
From this discussion you might predict the potassium supplementation with
decreased blood pressure. In fact, it does, and potassium supplementation
decreases blood pressure in most patients by about as much as starting doses
of most antihypertensive medications.
I hope this helps,
I. David Weiner, M.D.
March 27, 2008
Dr. Weiner,
I was going through your handout from last year and was confused
by one of the statements. “A urine protein by dipstick of 100 mg/dL with a sp.
Gr. Of 1.030 may indicate less proteinuria than a dipstick protein of 30 mg/dL
with sp. Gr. Of 1.005.” I think I may understand what you are thinking with the
specific gravities. Just because one urine specific gravity is higher or more
concentrated than the other doesn’t necessarily mean there is more proteinuria –
just that there is more solute that doesn’t have to be protein. But if you look
at the urine dipstick of 100 vs. 30 how is that not more protein present in the
urine? Thanks for the help.
- I think the issue here is to understand what urine specific gravity
measures. The specific gravity is essentially the weight of 1 mL of the
urine, measured in grams. Pure water, water without any other solutes such
as sodium and urea, weighs 1.0 g. Urine has many other solutes in it in
addition to water, and as a result ways more than 1 g per milliliter. The
most important solutes that increases the "weight" of urine is urea. As a
result, the specific gravity essentially measures the concentration of urea,
in addition to other solutes, in the urine.
The most important determination factor determining the concentration of
urea in the urine is how much water is reabsorbed in the collecting duct
through the ADH-regulated water channels. When more water is reabsorbed the
urea concentration is increased, resulting in an increased urine specific
gravity. When less water is reabsorbed, the urea concentration urine is
decreased and the specific gravity is decreased.
As a result, the urine specific gravity provides an indication, actually
an "inverse" indication, of the urine volume. A high specific gravity means
the more water was reabsorbed in the collecting duct and consequently that
the total urine volume is decreased. A low specific gravity indicates the
opposite and indicates a high urine volume.
Thus, the patient with a high urine specific gravity, i.e., 1.030, has a
low urine volume. Even though this patient may have a higher concentration
of protein in the urine, the absolute amount of protein (concentration
multiplied by volume) may be decreased. The patient with a lower urine
protein concentration may actually have a higher total amount of protein in
the urine if the total volume of the urine is substantially elevated.
I did get the impression from your question that you thought that the
protein concentration the urine may contribute to the specific gravity.
Because of physicochemical interactions, the urine protein concentration
actually has very little effect on the urine specific gravity.
I hope this helps. Please let me know if it is still unclear.
I. David Weiner, M.D.
March 13, 2008
Dr. Weiner, In the 24-hour creatinine clearance equation, I
don't understand the "/100" term in the denominator. I saw the explanation you
gave on the Q&A site, but I'm still confused. It seems that since concentration
is in the numerator and denominator, then concentration should cancel out and
there is no need for that correction. What are the units of the terms in the
equation (knowing the units may help to understand how everything cancels out to
get a clearance in ml/min)? Thank you.
-
The issue solely has to do with the units of measurement.
Urine creatinine is typically measured in mg/dl. Urine volume in ml
per day, but is converted to dl/day for the calculation. 1 day = 1440
min. Serum creatinine in mg/dl.
-
You want the answer in ml/min. Basically, since most of the
units of volume in equation are in dl, and you want the answer in ml, you
have to adjust by a factor of 100 (ratio of dl to ml).
I. David Weiner, M.D.
March 4, 2008
I had a question about yesterday's lecture. You stated that
increased ICP associated with hyponatremia leads to decreased cerebral perfusion
pressure. This is opposite of what we learned in systemic pathology, where they
said that increased intracranial pressure caused increased blood pressure with
decreased heart rate (the Cushing reaction). I was hoping you could clear up why
hyponatremia causes a different response. Thank you!
-
The difference is whether you are referring to systemic
blood pressure or cerebral perfusion pressure. While systemic bp can
increase, the Cushing response, with an excessive increase in intracranial
pressure the net cerebral perfusion pressure actually decreases,
leading to decreased blood flow to the brain and anoxic injury.
I. David Weiner, M.D.
March 4, 2008
Dear Dr. Weiner,
I have a question regarding serum creatinine and the GFR.
Regarding your notes, the 2007 handout states that "when renal function is
changing estimates of renal function based on the serum creatinine lag behind
the actual GFR by approximately 2 to three days." However, if this is the case,
I am questioning how you would use the serum creatinine provided by the lab data
in a patient who is ill to determine their renal function. If the patient is
ill, but the creatinine level was in the normal range, I am uncomfortable saying
that the patient's kidney function is normal since the GFR could be changing and
this would not be reflected in the serum creatinine level. Also, I was
wondering how you would apply the BUN lab values since urea metabolism,
according to your notes, can be inaccurate due to the patient's condition and/or
medications? Therefore, as a clinician, can you determine if this patient has
normal kidney function or is more testing and/or observation required? I
imagine that the whole patent's scenario would be analyzed, but I am just
questions what I should do with the lab data provided to avoid "brain stem
medicine." :)
Thanks for taking the time to answer my question. :)
Best regards,
-
Your analysis is correct. A normal creatinine does not always indicate
normal renal function, particularly in a patient who is acutely ill. A good
clinician takes into account multiple factors, including amount of muscle
mass and whether the creatinine is going up, down or staying the same. If
the creatinine is stable and the patient has a reasonably normal amount of
muscle mass, then the creatinine and the eGFR (from the MDRD formula) are
reasonably good predictors of relatively normal renal function.
The BUN, as you correctly state, has even more factors which can cause its
level to be incorrect.
As an astute clinician your goal is to take into account many factors,
including age, muscle mass, current creatinine, trend in the creatinine and
recent exposure to medications which may alter renal function. You may also
want to take into account the response to medications that alter renal
function, such as diuretics. The patient with low urine volume who does not
respond normally to diuretics is likely to have decreased renal function,
even if the serum creatinine is "normal." This is particularly true in
patients in the ICU - something about being sick and in the ICU seems to
result in suppression of muscle metabolism and result in decreased
creatinine production rates. This then causes the serum creatinine to
underestimate the degree of renal insufficiency. However, this latter
concern is something I typically worry about teaching to house-staff and
fellows, not medical students!
I hope this helps.
I. David Weiner, M.D.
March 2, 2008
Hello Dr. Weiner,
I have a quick question regarding proteinuria. I was
going through the notes from 2007, in the text format, and came across a couple
sentences in the "Assessment of Renal Function" lecture that confused me. "The
average person excretes approx 1 gm/d of creatinine, and a urine protein to
creatinine ratio of 2 mg protein per mg creatinine is predictive of a urine
protein excretion rate of 2 g/d." This sentence is under the "proteinuria"
section.
I don't understand when you would use this rough
estimate to predict proteinuria. Since the normal excretion of protein is
around 150mg/d, I am confused as to when this "formula" would apply and when the
protein in the urine would ever get as high as 2g/d (maybe in glomerular
injury?). Thank you for your time.
- You would use this formula to estimate the amount of proteinuria in
someone with known or suspected glomerular diseases that result in increased
proteinuria. The rate of creatinine excretion is relatively constant
in a given person, so this gives a way to measure baseline proteinuria and
then to assess response to treatment. It is much easier for a person
to give a single urine specimen than to have to collect all urine for 24
hours.
- Since the average rate of creatinine excretion for a person is ~1 gm/d,
a urine protein:creatinine ratio of 2:1 suggests a urine protein excretion
rate of ~2 gm/d. Of course, many people have creatinine rates higher
or lower than 1 gm/d, making the urine protein:creatinine ratio an inexact
measure of actual proteinuria. Nevertheless, it is useful as an
estimate and can be easily used to follow responses to treatments.
I. David Weiner, M.D.
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