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 2005
Wednesday, March 9
Dr. Weiner,
I did not catch what the prognosis is for SLE membranous class 5, doing an
internet search I found the answer to be FAIR. Class 4 diffuse proliferative I
also found to have a FAIR prognosis (in my notes I wrote it had the worst of all
of them). What is the prognosis for class 5 and how does this compare to class
4?
Thanks
- The prognosis for Class IV lupus nephritis in the absence of therapy is
much worse than for any of the other classes of lupus nephritis. In
the absence of therapy, few with severe class IV will live more than 1-2
years, and 50% of all patients with class IV lupus nephritis will die within
5 years. Without therapy, most will progress within a short time
period, usually measured in months, to end-stage renal disease.
Fortunately, therapy with immunosuppressives has greatly improved this
prognosis, but at the cost of side-effects of these medications and their
financial cost.
Class V lupus nephritis has a much better prognosis, with relatively
fewer patients developing end-stage renal disease and a much lower mortality
rate. The typical complication is proteinuria and the nephrotic
syndrome. Occasional patients with Class V lupus nephritis will
develop chronic kidney disease and may progress to end-stage renal disease,
but this is less predictable and less common than in Class IV lupus
nephritis.
I. David Weiner, M.D.
Tuesday, March 8
A few questions from the Sodium lecture:
1. I don't understand why the total body K+ must be considered when
evaluating the serum sodium concentration.
2. As for the relationship between enuresis and hyponatremia, is this
because you secrete less ADH at light and are reabsorbing less Na from the
nocturnal urine?
Thanks a bunch,
- The importance of total body K+ is not intuitively obvious, I agree.
Let me see if I can take you through the thought process.
Intracellular osmolality equals extracellular osmolality.
Intracellular potassium is the main determinant of intracellular osmolality.
Moreover, ~98-99% of total body potassium is intracellular. Thus,
deficits of total body potassium can lead to decreased intracellular
potassium, which decreases intracellular osmolality. If intracellular
osmolality is decreased, then extracellular osmolality also decreases,
because of water movement from the intracellular to the extracellular
compartment. Since sodium is the primary determinant of extracellular
osmolality, if extracellular osmolality is decreased then serum sodium will
be decreased.
You also want to recognize, however, that the majority of cases of
hyponatremia are not due to potassium deficits, and are related to the other
causes that we talked about in class.
- The relationship between enuresis and hyponatremia is that they are both
related to abnormal ADH metabolism in many cases.
Enuresis is frequently due to failure of the normal increase in ADH
levels at night time. Under normal conditions, ADH increases at night,
decreasing nocturnal urine volume and enabling one to sleep through the
night without experiencing a "full bladder" and having to urinate. The
lack of the nocturnal increase in ADH results in greater rates of urine
formation at night, a "full bladder" and, if the individual does not awaken
in response to the full bladder, enuresis.
Hyponatremia is, in many cases, due to elevated ADH levels throughout the
day, which results in increased renal water retention and hyponatremia.
I hope this helps.
I. David Weiner, M.D.
Monday, March 7, 2005
Dr. Weiner,
Since aldosterone deficiency can lead to renal sodium losses,
can it also lead to to hyponatremia?
-
In general, aldosterone deficiency can lead to renal sodium
losses. This is due to decreased expression of critical sodium
transporters, particularly the sodium channels in the collecting duct and
the thiazide-sensitive NaCl cotransporter in the distal convoluted tubule.
But, this does not lead to hyponatremia in most cases.
This is due to exquisite sensitivity of pituitary ADH release to changes in
plasma osmolality, with changes as small as 1% resulting in changes in ADH
release.
Sodium losses, if moderate, lead to a slight, clinically
undetectable decrease in serum sodium. Since plasma sodium is the
primary determinant of plasma osmolality, there is a parallel decrease in
plasma osmolality. This then decreases ADH release. Decreased
ADH release results in less water reabsorption in the collecting duct, and
excretion of more H2O molecules in the urine. ADH has minimal effects
on renal sodium transport. The net effect of the decreased ADH release
is excretion of free water, which then results in an increase in the serum
sodium concentration. Consequently, there is no change in the serum
sodium.
However, if the sodium losses are high, resulting in
substantial, 10-15%, decreases in plasma volume, then the volume-sensitive
component of ADH release is stimulated, increasing ADH release. The
increased ADH release results in renal water retention, increasing plasma
volume, but also "diluting" plasma sodium and decreasing plasma sodium
concentration.
The net effect of sodium losses from hypoaldosteronism is
thus related to the differential regulation of ADH release. ADH
release is exquisitely sensitive to small to changes in plasma osmolality.
Small changes in plasma volume do not cause much change in ADH release, but
large, 10-15%, changes do increase ADH release. The magnitude of ADH
release in response to large plasma volume changes is greater than the
magnitude of the effect of osmolality-related release. Thus, in the
event of large volume depletion and hyponatremia, the net effect is
increased ADH release. In the event of small decreases in plasma
volume and coexisting hyponatremia, the net effect is decreased ADH release.
I. David Weiner, M.D.
Monday, February 1, 2005
Dr. Weiner,
Thank you for your prompt response to my previous questions. I had another
question today while reviewing your lecture.
In hyponatremia caused by decreased EABV, is the pathophysiology behind
nephrotic syndrome and liver failure that vascular osmotic pressure is decreased
due to lack of plasma proteins such as albumin which will lead to "third
spacing?"
Would you briefly remind me how hypothyroidism affects sodium/water excretion by
the kidneys? Does it stimulate ADH
release?
Thanks,
- At a simple and conceptual level, you are correct that the
pathophysiology underlying the decreased EABV (effective arterial blood
volume) seen in nephrotic syndrome, liver disease and CHF is the lack of
plasma proteins leading to "third spacing" of fluids. This then is
perceived as a decreased blood volume and stimulates release of
counter-regulatory neurohormones that seek to increase plasma volume.
The
clinical problem, however, is that actual measurements of plasma volume show
that total volume is generally increased. Thus, a complete
understanding of why the body is sensing a decreased EABV when, in fact,
actual blood volume is increased, is still lacking. When we figure
this out, our ability to take care of these patients will be improved -
effective care is based on accurate understandings of the underlying
pathophysiology!
- Hypothyroidism appear to cause hyponatremia by impairing normal
development and activity of the transport mechanism involved in the distal
convoluted tubule and generation of a dilute urine. As a result, the
person cannot excrete excess water loads, and is susceptible to euvolemic
hyponatremia. Hypothyroidism does not have direct effects on ADH
release.
I. David Weiner, M.D.
Monday, January 31, 2005
Dr. Weiner,
I encountered a couple of questions when reviewing your lectures.
1. Why is specific gravity increased and urine osmolality higher in
prerenal dz in comparison with glomerular disease? Is this due to low urine
volume? I would think if the glomerulus is reabsorbing over 99% of Na, the
osmolality would be low.
2. Would you explain what you meant when you wrote: FE Na only is
useful only if tubules are maximally reabsorbing?
- The major component of urine osmolality, and therefore specific gravity,
is NOT sodium, but is urea, a nitrogen waste product, and other waste
products of metabolism. When the kidney reabsorbs water in the
collecting duct in order to minimize urine volume, these compounds,
generally, are not reabsorbed in parallel, and their concentration
increases. The increased concentration of these compounds is what
results in the increased osmolality and specific gravity.
- I think that what is present on the handout is "FE Na only tells is
tubules are maximally reabsorbing Na+," which is slightly, but significantly,
different than what you asked. In particular, there are conditions other
than pre-renal azotemia that result in stimulation of renal tubular sodium
reabsorption, and therefore result in a low FE Na. One example is acute
glomerulonephritis. Similarly, there are conditions other than ATN that
result in a high FE Na, such as acute tubulointerstitial nephritis.
The benefit of using the FE Na is that it helps to exclude diagnosis.
For example, the patient with oliguria acute renal failure who has not
received any diuretics and has a high FE Na is very unlikely to have
intravascular volume depletion and pre-renal azotemia as the cause of
the acute renal failure.
I. David Weiner, M.D.
Sunday, January 30, 2005
Dr. Weiner,
When I was reviewing the acute renal failure lecture I was confused by the
complications that occur in ARF. Could you please explain to me why there is
a depressed immune system increasing the risk for sepsis, an increased risk
of respiratory failure, and an increased risk of bleeding in a patient with
ARF.
Thanks,
- In renal failure, there is an impaired ability to excrete water-soluble
waste products. These accumulate in blood and in tissues. Some
of these impair the immune system, resulting in immunosuppression and an
increased risk of sepsis and other infections. Some suppress
respiration, and in conjunction with the immunosuppressive effect that
increases the risk of hospital-acquired pneumonia, which increases ,
increase the risk of respiratory failure. Others impair platelet
function, resulting in an increased risk of bleeding.
- Unfortunately, at present, we do not which of the potentially millions
of compounds whose excretion is inadequate in renal failure leads to each of
these complications. Dialysis, by replacing normal kidney function
with an "artificial kidney" improves, but does not fully correct these
problems. In part, this is because we can't, at least yet, measure the
levels of these "toxins."
I. David Weiner, M.D.
Saturday, January 29, 2005
4:29 p.m.
Hi Dr. Weiner,
I had a couple of questions regarding the Hyponatremia chart on page 2 of the
Sodium Handout.
Why does sodium remain unchanged and water increase in euvolemia? I
understand SIADH increases water retention in the body, but I thought the
relative concentration of sodium would fall as a result.
Also, I don't understand why thiazide diuretics, adrenal insufficiency and
hypothyroidism would fall under euvolemia, since I thought they would cause a
decrease in Na in the body (rather than leaving Na normal).
Thanks in advance,
- In SIADH, there is decreased total body sodium, but, because of the
water retention physical examination reveals a normal volume status by
physical examination.
- Thiazide diuretics can cause hypovolemic hyponatremia. Because
they are relatively mild diuretics, however, this is relatively uncommon.
More common is that they block the DCT ability to generate a dilute urine,
which, if combined with excess water intake, results in hyponatremia.
In this condition, volume status is usually normal.
In adrenal
insufficiency and hypothyroidism, overall sodium handling is generally
normal. This is due to sodium transport in other regions of the
nephron other than the DCT. However, DCT ability to generate a dilute
urine is decreased, leading to the possible generation of euvolemic
hyponatremia in individuals whose water intake is excessive.
I. David Weiner, M.D.
Saturday, January 29, 2005
2:31 p.m.
Here are a few more questions I have from lecture. I don't know if you know
but your website is not properly functioning today.
Thanks again.
Can you further explain how sepsis, hepatorenal syndrome (also what is it?),
AII- ACE-I and ARB, and PG?s- NSAIDS and COX-2 cause blood to be shunted away
from kidneys in prerenal azotemia? I would think sepsis effects are thru
vasodilation and overall hypotension, but the other mechanisms I am not sure I
understand the notes I wrote in class.
Can you explain why emergent dialysis would be used and how it would correct
each of the following: pulmonary edema, acid base disorders- met. Alkalosis, and
anemia with volume overload?
In euvolemic hyponatremia how does hypothyroidism and adrenal insufficiency
cause the kidneys to not be able to dilute urine? Is the adrenal insufficiency
mechanism due to low aldosterone resulting in low Na+ reabsorption and thus low
water reabsorption causing hypotension? This doesn?t sound right b/c it is a
euvolemic condition. What about hypothyroidism?
Can you explain the mechanism of CHF, liver disease and nephritic (sic) syndrome
in volume overload as it pertains to inappropriate ADH?
- Sorry about the web-site being temporarily down. It is now back
up. I had gone over my limit for server space, and had to delete some
of the files that are used for courses that are not currently in progress.
- The specific mechanism(s) through which sepsis and the hepatorenal
syndrome result in blood being 'shunted' away from the kidneys are not
completely understood, even by people that have studied these processes for
their entire careers. There is hypotension, and there is peripheral
vasodilation, but at the same time there is renal vasoconstriction.
Thus, even though cardiac output is increased, renal perfusion is decreasedd.
The specific mechanism underlying the renal vasoconstriction is not well
understood at present. At this point in time, the best that we can say
is only that it occurs, and that it is important in clinical medicine.
Auto-regulation of the glomerular filtration rate in response to
variations in renal perfusion pressure and in intravascular volume is an
important adaptation to common clinical conditions. This process
involves angiotensin II (AII) stimulating vasoconstriction of the efferent
arteriole. Thus, blocking AII formation, with ACE-I's, or AII's
activation of its receptor, with ARB's, blocks autoregulation of GFR, and
can lead to acute decreases in GFR in these conditions. Prostaglandin
formation is important for the efferent arteriole to respond to AII.
Accordingly, blocking prostaglandin production, with either NSAIDs or
COX-2's, can also result in acute renal failure in these conditions.
The conditions, again, in which autoregulation of GFR occur, include
intravascular volume depletion, hypotension and renal artery stenosis.
In renal artery stenosis, the systemic BP may be normal, or even high, but,
because of the obstructive lesion in the renal artery, the renal perfusion
pressure is low, and autoregulation is necessary to maintain GFR. With
unilateral renal artery stenosis, the change in total GFR due to the
decrease in GFR in the kidney with renal artery stenosis may not be easily
detected. However, with bilateral renal artery stenosis, the decrease
in total GFR is easy to observe.
- Adrenal insufficiency and hypothyroidism appear to cause hyponatremia by
impairing normal development and activity of the transport mechanism
involved in the distal convoluted tubule and generation of a dilute urine.
As a result, the person cannot excrete excess water loads, and is
susceptible to euvolemic hyponatremia.
- In volume overloaded hyponatremia due to CHF, liver disease and
nephrotic (not nephritic) syndrome, the person's body perceives,
incorrectly, that they are volume depleted. This occurs despite the
presence of multiple measures of volume overload, such as elevated JVP,
ascites and peripheral edema. If one measures hormones involved in
preventing hypotension and hypovolemia, such as aldosterone, catecholamines
and ADH, one finds that they are elevated in these conditions. Because
ADH is elevated, the person has an impaired ability to excrete free water,
and can develop volume-overloaded hyponatremia.
- These conditions are very different from SIADH. By convention, and
definition, SIADH has a normal volume status.
Why, you might ask, does SIADH have a normal volume status even though
elevated ADH levels stimulate water retention? When the ADH stimulates
water retention, this increases plasma volume, which then activates central
volume and pressure sensors, which results in stimulation of renal sodium
excretion. The net effect is hyponatremia without an
increased net volume.
I. David Weiner, M.D.
Friday, January 28, 2005
5:12 p.m.
Dr. Weiner,
I have a few questions regarding the notes as stated below. I am sure I will
have more as I review more of the material this weekend. Thank you for offering
this online questions service, it is very much appreciated.
What do you mean by the ratio of protein to creatinine in the random urine
specimen can be used to estimate the rate of protein excretion. The use of the
creatinine measurement corrects variations in urine volume.??
Could you further explain why you should be wary of serum creatinine
measurements when production does not equal excretion (how would you know this
is the case?) and when creatinine production is not normal (abnormal muscle
mass, cachexia, leg amputation?
Respectfully,
- The rate of urinary protein excretion is relatively constant during the
day. However, urine volume is not. As a result, the absolute
concentration fo urinary protein changes as the urine volume changes.
For example, an increased urine volume will decrease the urine protein
concentration, event though the the rate of urine protein production is
constant.
Since the rate of urinary creatinine excretion is constant during the
day, the urinary creatinine concentration provides information regarding
relative changes in urine volume. For example, a two-fold increase in
urine volume, as may occur after drinking several cups of coffee or lots of
lemonade or ice-tea, will decrease the urine creatinine concentration by a
proportional amount (50%).
By dividing the urine protein concentration by the urine creatinine
concentration, one obtains a measure of the urinary protein excretion rate
that is independent of changes in urine volume. This enables one to
follow changes in urinary protein excretion in a given patient over time in
response to therapeutic interventions.
- Regarding the use of the serum creatinine to assess renal function, the
serum creatinine is proportional to the glomerular filtration rate only when
creatinine production equals creatinine excretion.
An example might be the level of water in a colander when washing
spaghetti noodles. At steady-state, there will be a constant level of
water in the colander. If one blocks half of colander, the water level
will gradually rise to twice the initial level. When the level has
stabilized, one can tell, because the level is twice as high, that the
surface area for water to exit the colander is only half as much.
You should also note, however, that one second after blocking half of the
colander's surface area, the water of level may not have perceptibly
changed. Similarly, if one turns the water faucet off, it takes a
period of time for the water to drain out of the colander. During that
time, the water level does not reflect the colander's surface area available
for filtration.
Similar considerations apply for the kidney, glomerular filtration rate
and serum creatinine. If a patient undergoes bilateral kidney removal
(nephrectomy), the GFR 1 minute after the nephrectomy is zero.
However, the serum creatinine is unlikely to be measurably changed.
- These above discussions should help you with why you should be wary of using
the serum creatinine to estimate GFR whenever the creatinine production does not
equal excretion. You can tell this because the serum creatinine is
changing from day to day.
We routinely using the serum creatinine to estimate
GFR. We do this because 24 hour urine collections to quantify the rate of
creatinine excretion are cumbersome, inconvenient and frequently performed
incorrectly.
Because of this, we have found that in most individuals we can accurately
predict the rate of creatinine production from a variety of factors. If
the serum creatinine is constant, then creatinine excretion equals creatinine
production. this allows you to use the predicted creatinine production
rate in conjunction with the serum creatinine to estimate GFR. This has
been incorporated into the two formulas that we discussed in class, the
Cockcroft-Gault formula and the MDRD formula.
However, these formulas also assume relatively normal amounts of creatinine
production by the given individual. Since muscles produce creatinine, it
should be obvious that abnormal amounts of muscles will result in abnormal rates
of creatinine production. None of the formulas were generated to take into
account body-builders that have twice the muscle mass of an average individual.
Nor do they take into account the individual who has had bilateral lower
extremity amputations. Remember, the greatest mass of muscle in the body
is present in the thighs. Thus, these formulas are less accurate when used
for individuals with obviously abnormal amounts of muscle.
I. David Weiner, M.D.
Questions and Answers from 2004
Can you clear up the 24 hour spot test for protein for me? Is it a dipstick
for 24 hours or is it something else? Also, is this the same thing as the gold
standard 24 hr urinalysis for determining protein excretion?
- There are two quantitative tests for urinary protein excretion.
- The 24 hour urine for protein, the 'gold standard' that you referred to
in your question. This is, of course, somewhat inconvenient for the patient.
- The other is a random urine sample, in which both protein and creatinine
are measured. The result is then reported as mg protein per mg creatinine.
The use of the creatinine corrects for variations in urine concentration.
- The only way that a urine 'dipstick' is done is on a freshly voided
urine sample.
David Weiner, M.D.
What role do thyroid hormones have in the kidney? I am having trouble
understanding why hypothyroidism plays a role w/ euvolemic hyponatremia.
-
Thyroid hormone is probably necessary for full
functioning of distal convoluted cells involved in generating a dilute
urine. This is probably because thyroid hormone has a potent regulatory
effect on Na-K-ATPase, a major protein regulating sodium reabsorption in the
DCT. However, the complete mechanism is not well understood.
David Weiner, M.D.
I have a quick question about today's lecture. As one of the potential causes
of acute renal failure (specifically prerenal azotemia), you have listed
"bilateral renal artery stenosis with use of an ACE-I or ARB that prevents
autoregulation of renal blood flow". In class, though, you seemed to list
stenosis and ACE-I and ARB's as separate causes for acute renal failure. Could
stenosis by itself, without the use of ACE-I's or ARB's, potentially cause
prenal azotemia? Likewise, could ACE-I's or ARB's, independent of stenosis,
cause prenal azotemia? I am confused--perhaps I missed something you said in
class--I thought that you listed hormonal imbalances (ie caused by ARB's or
ACE-I) as separate from stenosis as potential causes for prerenal azotemia.
-
Renal artery stenosis or ACE-I or ARB's, by themselves, almost never cause
acute renal failure.
Under normal conditions, Angiotensin II does not play a major role in
regulating glomerular filtration. Thus, under normal conditions, ACE-I's or
ARB's only cause small changes in GFR, less then 20-25%.
Under conditions in which glomerular perfusion pressure is decreased,
such as with renal artery stenosis or hypotension, or under conditions of
intravascular volume depletion angiotensin II becomes important for
determining GFR.
As a result, ACE-I's or ARB's cause ARF in people with renal artery
stenosis, hypotension or intravascular volume depletion. If a person
develops ARF after starting an ACE-I or an ARB, then these conditions should
be considered.
I. David Weiner, M.D.
Questions and Answers from previous years
(1) Why do patients with chronic renal disease develop GI bleeds?
-
Chronic renal disease impairs platelet function, thereby resulting in a generalized increased propensity to
bleed, thus increasing the risk of GI bleeds and increasing the amount of
chronic blood lost into the stool. In addition, patients with chronic
renal disease frequently develop constipation. The friction of the
stool along the colon may "irritate" the colon and increase GI
blood loss.
(2) What is the mechanism for immune suppression in chronic renal disease?
Does this have to do with erythropoeitin "cross-reacting" or affecting
white blood cell production in bone marrow?
-
The exact mechanism is not known. Hundreds of compounds have been
found to be either increased or decreased in abundance in the blood in
chronic renal disease. Understanding which is the "primary"
cause of the impaired immune system has been extremely difficult for
scientists to determine.
-
Erythropoietin is the not the mechanism, however. It has minimal to
no effects on WBC production, and giving erythropoietin to patients does not
reverse the immune suppression. Moreover, WBC production is normal in
chronic renal disease.
I. David Weiner, M.D.
(3) Followup on #1: Are the mechanisms known for the impaired platelet
function and constipation in patients with chronic renal disease?
-
We only have hints as to the complete mechanism underlying these
processes. Platelet dysfunction appears to be related to both retained
compounds and to the deficiency of certain compounds. Dialysis
improves the platelet dysfunction, suggesting that some low-molecular weight
molecule that the kidneys normally remove accumulates in renal failure and
inhibits platelet function. Administering cryoprecipitate or dDAVP, a
V2-subtype specific vasopressin agonist, also improves platelet
function. Similarly, high dose estrogen is also helpful.
Unfortunately, the exact mechanism remains elusive.
(4) By what mechanism does hyperkalemia slow the conduction velocity of
electrical signals, especially when one component of the signal, the
repolarization, is faster?
(5) How does hypokalemia cause increased sensitivity to arrhythmias? It would
seem that by making the resting membrane potential more negative, myocytes would
require a greater stimulus to reach threshold, and would be less sensitive.
I. David Weiner, M.D.
In your lecture, you said that if someone taking a thiazide diuretic drinks a
lot of water, they won't be able to get rid of the excess h20 in their urine b/c
the mechanism where you make dilute urine (in the distal convoluted tubule) is
blocked.
Perhaps I misinterpreted your words, but does this mean that the volume of urine
will not increase despite an increased water intake? if this is the case,
i don't understand why urine volume would not increase since no water
reabsorption takes place in the dct (which is the site of action for thiazide
diuretics).
-
Drinking large amounts of water, if not accompanied by sodium and if the
kidneys are not working, will decrease the serum sodium
concentration.
-
In order to return the serum sodium back to normal, the kidneys must
generate urine that has substantially less sodium and has a lower osmolality
than the serum. Remember, serum sodium concentration is
determined by the ratio of the total amount of sodium to the total amount of
water.
-
The DCT is the only segment in the kidney that has the ability to generate
urine with a sodium concentration significantly below that of serum.
It does so because of sodium reabsorption through the NaCl cotransporter and
because there is no significant water reabsorption, due to a lack of
aquaporin expression.
-
Thiazide diuretics will increase the urine volume by blocking the sodium
chloride cotransporter in the DCT. This increases sodium
delivery to more downstream nephron segments, which, by increasing luminal
osmolality, decreases water reabsorption. As a result, urine volume
increases.
-
However, by blocking the only site in the kidney with the ability to
decrease urine sodium substantially below serum osmolality, thiazide
diuretics prevent formation of a dilute urine with a low sodium
concentration. This then prevents the kidney from enacting recovery
from the hyponatremia.
I. David Weiner, M.D.
Posted May 2 2:09 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1. in the glomerular dz lecture, you mentioned that Ang 2 leads to
proteinuria and therefore pts. should use an ACE inhibitor....please explain how
Ang 2 causes proteinuria?
-
Angiotensin II (AII) appears to cause proteinuria by altering the charge
structure of the glomerular basement membrane (GBM). In particular,
AII appears to decrease the negative charges that are normally present and
normally function to inhibit "passage" of negatively charged
proteins. AII also appears to slightly increase the size of the pores
that are normally present in the GBM. The net effect of these
processes is to increase the amount of protein that crosses the GBM.
2. in the review, you stated that Cr clearance
actually overestimates GFR b/c of minimal Cr secretion...then you mentioned that
b/c this increases urine Cr and decreases blood Cr, there is no overall change
in GFR? Can you please clear this up for me?
-
Creatinine gets into the urine by two separate mechanisms.
-
The first, and primary, mechanism is through glomerular filtration.
When GFR is ml/min (for example), ml/min of plasma is filtered and
the creatinine from this ml of plasma appears in the luminal fluid in
the proximal tubule. Because there is no reabsorption of creatinine,
all of this creatinine will appear in the final urine.
-
The second mechanism is through tubular creatinine secretion that occurs
in the proximal tubule. Under normal conditions this is a fairly minor
mechanism.
-
However, the presence of creatinine secretion means that the amount of
creatinine in the urine exceeds the amount that is filtered at the
glomerulus. In other words, creatinine excretion exceeds glomerular
filtration. It also means that there are two components to renal
creatinine clearance, glomerular filtration and tubular secretion. As
a result, creatinine clearance exceeds glomerular filtration.
-
Under normal conditions the amount of creatinine secretion is sufficiently
small that it does not interfere with the ability to use creatinine
clearance as a convenient measure of glomerular filtration rate.
-
Two conditions exist where this is "less true." First, as
GFR decreases, the proportion of creatinine clearance that occurs from
tubular secretion increases. When GFR is <20 ml/min (~20% of
baseline), as much as a third of creatinine clearance may be from tubular
secretion. For example, if "true" GFR is 10 ml/min, tubular
creatinine secretion may equal 5 ml/min, resulting in net creatinine
clearance of 15 ml/min. Thus, creatinine clearance is substantially
overestimating GFR.
-
A second clinical problem occurs if the patient begins taking
medications that interfere with tubular creatinine secretion. Examples
include cimetidine and trimethoprim. When a patient takes one of these
medications, the medication will inhibit tubular creatinine secretion.
This decreases renal creatinine clearance, and increases the plasma
creatinine level. With a normal GFR the relative amount of tubular
creatinine secretion is minimal, and the changes induced by these
medications will be minimal. However, if GFR is impaired for other
reasons, the relative contribution of tubular creatinine secretion is
increased, and blocking tubular creatinine secretion can cause a significant
increase in plasma creatinine. Note that this increase occurs in the
absence of a change in the GFR. If the clinician is not aware, they
may mistakenly interpret the increased creatinine level as a decreased GFR.
-
The clinician can differentiate whether the increased serum creatinine is
due to worsening of the GFR from inhibition of tubular creatinine secretion
by assessing whether another marker of GFR that is not secreted as
creatinine is changes in parallel with creatinine. Such a marker is
urea. If plasma creatinine increases, but urea (BUN) does not, this is
evidence that the change is due to decreased tubular creatinine
secretion. If both plasma creatinine and BUN increase proportionally,
then the changes are likely due to decreased GFR, and not to impaired
tubular creatinine secretion.
thanks so much for your time.
David Weiner, M.D.
Posted Apr 30 1:40 PM by MEDICAL STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
Dr. Weiner, our clinical dx test was rescheduled for this Friday now, so we may have a few more questions. We really
appreciate your help!!!
David Weiner, M.D.
Posted Apr 30 1:39 PM by MEDICAL STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
In class, you gave an example of a little old lady on thiazide diuretics who does not eat much sodium. If she went on thiazide
diuretics, did you say that she cannot make urine with only not sodium, and that she cannot get rid of the extra water since
losing Na simultaneously? How is she losing Na simultaneously? Could you please explain this concept? Thanks
-
Thiazide diuretics increase urinary sodium excretion because they inhibit the NaCl cotransporter present in the distal
convoluted tubule (DCT). This decreases DCT sodium reabsorption, leading to increased sodium delivery to the
collecting duct. The collecting duct is unable to increase its sodium reabsorption sufficiently to reabsorb the excess
sodium delivered to it. As a result, urinary sodium excretion increases.
-
The second effect of thiazide diuretics is to decrease the kidney's ability to excrete a dilute urine. Remember that a dilute
urine is formed by the DCT. Urine that comes out of the loop of Henle to the DCT has an osmolality very similar to
plasma osmolality. Under normal conditions the DCT can reabsorb sodium, but cannot reabsorb water. As a result, urine
that leaves the DCT is diluted when compared with plasma.
-
Thiazide diuretics partially inhibit the DCT's ability to reabsorb sodium and have no effect on DCT water transport. The
net effect is that thiazide diuretics inhibit the DCT's ability to generate a dilute urine. Since no other segment of the
nephron can generate a dilute urine, thiazide diuretics inhibit the kidney's ability to generate a dilute urine.
-
Because thiazide diuretics, when used in typical clinical doses, only partially inhibit DCT sodium reabsorption, they only
partially inhibit the kidney's ability to form a dilute urine.
-
Patients at the highest risk for this side effect are those with decreased GFR to start with who also have low dietary
sodium intake and high dietary water (fluid) intake. A "classic" example of this type of patient is the elderly patient eating
a low sodium diet (i.e., salt-free crackers) and drinking lots of tea (high fluid intake).
David Weiner, M.D.
Posted Apr 30 1:36 PM by MEDICAL STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.on page 4 of ARF lecture is a table. Could you please explain why the BUN/Cr ratio and
urine specific gravity are greater
with prerenal than with ATN?
-
Under normal conditions, the body produces ten-times more urea nitrogen (the "UN" of Blood Urea Nitrogen, BUN) than
creatinine. Both BUN and creatinine are, under normal conditions, filtered by the glomerulus in the process of glomerular
filtration and the amount of tubular filtration and secretion are relatively minor. As a result, their plasma levels remain in
a approximate 10:1 ratio of BUN:Cr.
-
However, certain conditions alter the tubular reabsorption of urea nitrogen. In particular, urine concentration requires
urea
reabsorption by the collecting duct. This decreases the urinary excretion of urea, and it increases the blood levels of urea
(BUN). In contrast, concentrating the urine does not alter tubular creatinine secretion/reabsorption. The net is that
conditions that require urinary concentration, such as IVV depletion, increase BUN out of proportion to Cr, resulting in an
increased BUN/Cr ratio. Pre-renal azotemia is such a condition.
-
In contrast, with ATN there are similar effects on both filtration and tubular handling of urea and creatinine. As a result,
the BUN/Cr ratio remains constant.
2.how does hypothyroidism and adrenal insufficiency contribute to euvolemic hyponatremia on page 2 of sodium d/o
lecture?
-
Normal levels of thyroid hormone and cortisol are needed for normal distal convoluted tubule (DCT) function. As
discussed a few questions above, the DCT is responsible for the kidney's ability to form a dilute urine. In the absence of
normal thyroid hormone or cortisol this ability may be partially lost, thereby predisposing patients to develop euvolemic
hyponatremia.
3. Why would the serum sodium be higher in the cases with 15% increase in vol/pressure (fig 1 on page 2 of sodium lecture).
Thanks a lot!
-
What figure 1 on page 2 of the sodium handout is trying to show is the
interaction between osmolality and vol/pressure on ADH release. Under
normal conditions, very small changes in osmolality induce changes in ADH
release. Life-threatening changes in vol/pressure can also change ADH
release. Life-threatening decreases in vol/pressure stimulate ADH release at
any given level of osmolality. It also shifts the ADH/osmolality curve
to the left. The net effect is to increase, quite substantially, ADH
release. ADH increases water reabsorption from the urine, thereby
concentrating the urine and decreasing urine volume. This serves to
minimize urinary fluid losses, and contribute to maintenance of plasma
volume/pressure.
-
Conversely, in volume overloaded - pressure overloaded conditions, ADH
release is inhibited. This decreases water reabsorption from the
urine, thereby increasing urine volume and promoting excretion of the excess
volume in the urine.
-
Hypernatremia does not occur because other volume-sensitive hormones, such
as epinephrine, norepinephrine, aldosterone, dopamine and atrial natriuretic
peptide (just to show-off and name a few) alter sodium transport, and will
increase urinary sodium excretion in volume/pressure overloaded conditions.
David Weiner, M.D.
Posted Apr 30 1:33 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.What exactly causes ESRF - ARF and CRF?
-
I'm not sure that I understand your question, but will try.
-
ESRD is renal disease that has progressed to the point where it is
irreversible and has caused sufficient renal damage that replacement of
renal function, either with dialysis or with a kidney transplant is
necessary to maintain health and prevent death.
-
ARF is an acute decrease in renal function. It typically occurs over
days. The decrease may be enough to require temporary use of dialysis,
but it does not have to be this severe.
-
CRF is a chronic decrease in renal function that is not severe enough to
require using dialysis or a renal transplant.
-
Each of these conditions has numerous causes. The most common causes
are: ESRD - diabetes mellitus or hypertension, ARF - hypotension or
nephrotoxic drugs, CRF - diabetes or hypertension.
2.How long does ARF last?
-
ARF can last a variable period of time. Sometimes ARF resolves
within a few days, and sometimes it takes a few weeks to resolve. The
longer ARF persists the less likely that it will ever resolve. If ARF
lasts longer than six weeks the chance of recovery becomes almost
zero. As a result, if ARF lasts more than six weeks we generally will
call it either CRF or ESRD.
How can patients with acute glomerulonephritis have
concentrated urine (pts with ATN and Acute interstitial nephritis cannot, so how can acute GN (p. 3 notes of ARF.)
-
The urine is frequently concentrated in acute glomerulonephritis, but not
always.
-
In brief, there is a decrease in the amount of NaCl and water filtered
because of the glomerular disease, but the tubules are relatively normal.
-
The tubules "sense" the decreased amount of filtered NaCl and
water, and interpret this to indicate that IVV is decreased.
-
They then respond by increasing reabsorption of NaCl and water in an
attempt to increase IVV volume. This
causes a concentrated urine that is decreased in volume.
-
In both ATN and acute interstitial nephritis tubular function is abnormal,
thereby preventing urine concentration. Urine concentration is a
complicated event that requires the loop of Henle to generate a hypertonic
medullary interstitium through the counter-current mechanism and the
collecting duct to be able to reabsorb water. In ATN and interstitial
nephritis these abilities are lost.
-
However, remember that urine volume may be low in ATN and interstitial
nephritis. If the kidneys are damaged severely enough the glomerular
filtration rate may go down to zero. No filtration, no urine
formation. Also, the damaged tubular cells may both
"fall-off" the basement membrane and "obstruct" the
tubular lumen downstream. The loss of tubular cells may also allow any
urine that has been filtered to "back-leak" from the tubular lumen
into the renal interstitium where it is reabsorbed into the capillaries and
returned, via the renal veins, to the systemic circulation. The
combination of these three processes can lead to very low urine volumes in
some cases of ATN or interstitial nephritis. However, remember that
because of the damaged tubular function the urine, although low in volume,
will not be concentrated.
3.If block
Ang 2 formation with prerenal cause of ARF, the Phydrostatic decreases and blood goes right through kidney without being
filtered. By saying that things don't get filtered, do you mean that nothing is secreted, excreted, or reabsorbed? It's as if the
kidney was never there? Thank you for answering these questions.
David Weiner, M.D.
Posted Apr 30 10:56 AM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
On page 2 of the glomerular d/o lecture, I am having a problem with understanding how hypoalbuminemia causes edema? If
there is less protein in the blood, why would MORE water go that area diffusion wise? Thank you
David Weiner, M.D.
Posted Apr 30 10:55 AM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.The K+ d/o lecture, is glucose in the extracellular compartment?
-
Glucose is present in both the extracellular and the intracellular
compartments. The purpose of extracellular glucose is to supply
glucose for cellular uptake for energy metabolism. Glucose gets from
the extracellular compartment to the intracellular compartment, in almost
all tissues except the brain, when insulin stimulates glucose uptake.
In the absence of insulin (type I diabetes mellitus) or when insulin
sensitivity is decreased/lost (type II diabetes mellitus) extracellular
glucose levels increase.
Why does it cause a redistribution of potassium to
extracellular?
-
When extracellular glucose levels increase plasma osmolality
increases. When osmolality increases cells shrink because water moves
from areas of high concentration (low osmolality) to low concentration (high
osmolality). The cell shrinkage then stimulates potassium release from
the cell, thereby moving potassium from the intracellular to the
extracellular compartment.
2. Is slowly progressive hematuria a chronic d/o and therefore IgA nephropathy is?
-
IgA nephropathy is a slowly progressive, chronic disorder, because it only
slowly progresses. If this definition sounds circular, it is. A
slowly progressive disorder is a disorder that is slowly progressive.
Duhhhhhh.
-
Hematuria itself is not damaging to renal tubules. Instead, it
appears to be a marker of underlying renal disease. Thus, the chronic
hematuria does not cause the chronic condition, it is only a symptom of the
underlying condition.
-
This differs from proteinuria. Proteinuria is both a symptom of the
underlying condition and also appears to directly cause progressive renal
disease.
Thank you for your help. David Weiner, M.D.
Posted Apr 30 10:50 AM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.(K d/o lecture) - Does the slower entry of calcium cause v fib? How does the decreased rate of depolarization cause v fib if v
fib is such a fast rate?
-
The VFib occurs as a net result of a variety of abnormalities in ion
transport that occur due to the hyperkalemia. The decreased rate of
depolarization contributes to the development of VFib by increasing the
chance that a subsequent electrical stimulation will occur during the
refractory period where the electrical stimulation can induce disordered
electrical activity. This then is VFib.
-
VFib only appears to be a rapid rate because ventricular myocyte
contraction is totally disorganized. Because contraction is
disorganized it appears to be fast, but results in no significant cardiac
output.
2. You mentioned that hypokalemia has an increased sensitivity to v fib or a fib, but does
hyperkalemia?
-
No. Hyperkalemia, if severe enough, causes VFib. This is
different from an increased sensitivity. Hypokalemia does not cause
ventricular arrhythmias, but makes it more likely that if an arrhythmia
occurs that it will convert from a benign arrhythmia into VFib, a lethal
arrhythmia.
Thank you
David Weiner, M.D.
Posted Apr 20 7:13 AM by STUDENT
In Reference to http://www.
medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1. WHY DOES ONE WANT TO SLOW THEIR GFR IN CHRONIC RENAL FAILURE? (THEY EAT
LESS PROTEIN TO KEEP IT FROM INCREASING).
-
Stimuli that cause short-term
stimulation of GFR are beneficial in the short-term. However, like many
short-term solutions, they tend to cause more long-term damage. An analogy
might be staying up late, or even pulling an all-nighter, before an exam.
While short-term this might be effective, long-term it would obviously be
detrimental to your health, and to your grades. The same is true for
preserving
GFR in the presence of renal insufficiency.
-
In truth, the details are
much more complicated. Short-term stimulation of GFR by protein, and by
many other causes, is associated with stimulation of nitric oxide,
TGF-beta, and many other cytokines that in the long-term are damaging to
the kidney.
2.HOW DOES THE PROGRESSION OF RENAL DISEASE CAUSE
PROTEINURIA?
-
You appear to have this
association backwards. Proteinuria can cause the progression of renal
disease over prolonged periods of time. Through a wide variety of
mechanisms, most of which remain incompletely defined, proteinuria,
especially in large amounts, appears to be nephrotoxic (damaging to the
kidney). As a result, therapeutic maneuvers that decrease proteinuria,
such as blocking angiotensin II formation with ACE-I's, appear to slow the
progression of renal disease.
3. DO WE ASSUME THAT ALL PATIENTS WITH ESRD HAVE HYPERTENSION SINCE THEY'RE
TOLD TO LIMIT FLUIDS TO PREVENT 'WORSENING OF HYPERTENSION?'
-
Essentially all patients with
chronic renal insufficiency (CRI) have hypertension. The hypertension both
results from the chronic renal insufficiency and contributes to the
progression of the chronic renal insufficiency. CRI causes hypertension
because of a decreased ability to excrete sodium and water, leading to IVV
overload and the development/worsening of hypertension.
THANKS
David Weiner,
M.D.
Posted Apr 20 7:11 AM by medical
students
In Reference to http://www.
medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.Dr. Weiner, does the localized hypertension produced from the renal
insufficiency
produce systemic hypertension or does the systemic hypertension coexist before?
This regards a previous question posted about the control of blood pressure and
chronic renal insufficiency.
2.Dr. Weiner, on page 2 of your chronic renal failure lecture, it states
"Whether ACE-1 are beneficial in individuals with renal disease but
<1gm/d of proteinuria.." is being studied. Will you please explain
this?
 |
ACE-I are beneficial in
laboratory
animals under almost all conditions of renal insufficiency. However, this
doesn't mean they will definitely be beneficial in humans. Clinical trials
are necessary to determine whether this is true, and under what conditions
it is true. At present, clinical trials have relatively definitively shown
that ACE-I are beneficial, above and beyond their effect on blood pressure
in patients with: |
-
Diabetes who have
any renal
disease, or
-
Patients without
diabetes but with more than 1 gm/d of proteinuria.
3. Are hypotension, tinting of skin, dehydration, and IVV depletion signs of
acute renal failure?
-
In
the patient with renal failure of unknown duration, hypotension, tenting of the
skin, dehydration and other signs of IVV depletion suggest that acute renal
failure is present, and that dehydration with subsequent "pre-renal
azotemia" is the etiology. The absence of these signs suggests that
pre-renal azotemia is not present, but does not exclude the possibility that
acute renal failure due to other causes (obstruction, acute tubular necrosis,
etc.) might be present.
-what would be signs of chronic renal failure then? Thank you for your
help!!!!
-
Chronic
renal failure is usually associated with signs of volume overload.Ý These include peripheral edema, pulmonary
edema, and hypertension.Ý However, these
signs are not very sensitive or specific, and their presence is of relatively
little help in differentiating acute from chronic renal failure.
David Weiner,
M.D.
Posted Apr 19 9:35 PM by group of
students
In Reference to http://www.
medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1. Is nephritis inflammatory versus nephrotic?
2. How do you know if it is fast, chronic, slow, or rapidly progressive?
3. Under the three patterns of IF, one was nothing, so not due to Ig, but
you said that it is associated with ANCA Ab with PAN. Isn't an ANCA Ab an Ig?
Thank you.
-
Yes, ANCA is an IgG
antibody. However, it does not localize to the glomerulus in rapidly
progressive glomerulonephritis due to ANCA. As a result, the
immunofluorescence pattern and the electron microscopy of the glomerulus
show patterns of little-to-none immunoglobulin deposition, a so-called
"pauci-immune glomerulonephritis."
David Weiner,
M.D.
Posted Apr 19 9:33 PM by group of
students
In Reference to http://www.
medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.On page 1 of glomerular d/o lecture, it says, "small amounts of
protein are filtered, but are reabsorbed by prox tubule." Also, it says
uptake of filtered proteins leads to chronic damage of proximal tubule??? So
does a normal person never filter proteins?
-
Under normal conditions we
all filter very small amounts of proteins. The amounts are so small,
however, that they do not lead to nephrotoxicity. It appears that you have
to filter large amounts of protein, that overload the "normal"
mechanisms that handle filtered protein, before "other"
mechanisms are activated that subsequently lead to nephrotoxicity.
2. Also, it says "magnitude of the proteinuria varies widely and is
influenced by GFR, plasma concentration of albumin and dietary protein
intake" Is it that the greater the plasma albumin and GFR, the more
proteinuria?
-
In general, everything else
equal, yes. The major protein present in proteinuria is albumin. Hence the
higher the serum albumin level, the more that will be filtered at the
glomerulus, the more will "show-up" in the urine, and the
greater the degree of proteinuria. Similarly, the higher the GFR, the more
glomeruli are present for albumin and other proteins to filter across.
However, the association between GFR and amount of proteinuria is less
tight. As the renal disease progresses, there is more damage to the
remaining glomeruli, leading to more proteinuria from the remaining
glomeruli. As a result, the level of proteinuria may remain relatively
constant despite progressive loss of GFR.
3.If IgA nephropathy and membranoproliferative GN is a nephritic syndrome,
why doesn't it have acute nephritic syndrome as a clinical feature?
-
Good question. IgA
nephropathy and membranoproliferative GN (MPGN) both present with
hematuria, and are therefore classified as nephritic. However, the
"intensity" of the inflammation is very low. Indeed, on renal
biopsy there are many fewer white blood cells present in the glomerulus.
The WBCs that are present are typically lymphocytes, as contrasted with a
large number of PMNs in conditions associated with RPGN (rapidly
progressive glomerulonephritis, i.e., "acute nephritic
syndrome"). Again, this difference is associated with a slower
progression of disease. Finally, IgA nephropathy and MPGN do not cause
"crescents." Crescents are a form of cellular and fibrous
"material" that forms between the parietal and visceral
epithelia of the glomerulus, are a marker of severe inflammation, and
probably contribute to loss of renal function. Crescents are almost always
seen in cases of RPGN.
4. Are there no "big holes" in the glomerulus in nephrotic
syndrome?
We thank you.
-
The holes that are present
in the glomerular basement membrane in the nephrotic syndrome are large
enough for proteins to pass through, but not large enough for RBC's to
pass through. In either case, the holes are too small to be seen either
with light or electron microscopy. However, they must be there, otherwise
how else could the proteins (in nephrotic conditions) or RBC (in nephritic
conditions) appear in the urine?
David Weiner,
M.D.
Posted Apr 18 8:24 AM by student
In Reference to http://medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
In the K d/o lecture, on page 4 is a graph. Is the x axis initially so
straight due to the K+ going from intracellular to extracellular to compensate
for hypokalemia?
Yes. In
response to potassium depletion there is redistribution of potassium from the intracellular
to the extracellular compartments in order to maintain a relatively normal
serum potassium and intra:extra-cellular potassium gradient.
David Weiner, M.D.
Posted Apr 18 8:23 AM by student
In Reference to http://medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.Are myocardial cells extra sensitive to arrhythmias which leads to
increased risk of vent fib due to the higher(less neg) membrane potential and
easier abilty to depolarize?
The less negative membrane potential that occurs in
hyperkalemia alters a number of cellular functions and parameters. One of these parameters is the rate of
calcium entry during the action potential.
The decreased rate of calcium entry leads to a number of abnormalities,
including decreased rate of action potential conduction and a decreased rate of depolarization. The resulting effects include the changes in the EKG that we
discussed in class, and, at the most extreme, the development of ventricular fibrillation.
2.Why is there a decrease in insulin sensitivity with hypokalemia if insulin
is an actual cause of hypokalemia? thank you
The changes in membrane potential with hypokalemia
alter pancreatic responsiveness to glucose, and, as a result, decrease pancreatic
glucose-stimulated insulin release.
This probably acts as a counter-regulatory mechanism to minimize
hypokalemia. In other words,
hypokalemia decreases insulin release.
This then inhibits insulin-stimulated cellular potassium uptake, thereby
minimizing any further hypokalemia.
David Weiner, M.D.
Posted Apr 18 8:22 AM by student
In Reference to http://medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
In the potassium d/o lecture, when insulin is added, is it given IV to go
intracellularly therefore drive the K+ into cells and to prevent hyperkalemia
in diabetes? How does insulin drive K+ inside cells?
Insulin has a number of effects that cause redistribution
of potassium from the extracellular space to the intracellular space. Perhaps most predominant is that it
stimulates the Na-K-ATPase that is present in almost all cells. This protein drives potassium uptake into
cells, and is responsible for the high intracellular potassium
concentration. By stimulating
Na-K-ATPase, insulin increases cellular potassium uptake and, thus, can be used
to treat hyperkalemia.
2. How does IVV depletion cause hypokalemia?
Intravascular volume depletion stimulates
aldosterone release. Aldosterone then
both stimulates cellular uptake of
potassium, by stimulating Na-K-ATPase, and it stimulates renal potassium
excretion into the urine. The net
effect is hypokalemia.
3.Is IVV depletion desired in CHF?
In CHF there is intravascular volume overload that
is no longer beneficial. Although
increased pre-load generally increases cardiac output, in decompensated CHF the
IVV overload is so extreme that it leads to: 1) pulmonary edema; 2) peripheral
edema; and, 3) sometimes decreased cardiac output from cardiac volume
overload that leads to decreased myocardial contractilility. As a result, diuretics to decrease IVV back towards
normal are a mainstay of CHF treatment.
4. Is secondary hyperaldosteronism due to Ang 2 response? from what? Thank
you for answering these question.
Secondary hyperaldosteronism occurs when excessive
aldosterone production/release/levels occurs in response to Angiotensin II
stimulation. Any cause of increased
Angiotensin II will cause secondary hyperaldosteronism. Examples include IVV depletion, congestive
heart failure, decompensated liver disease and the nephrotic syndrome.
David Weiner, M.D.
Posted Apr 18 7:07 AM by medical student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.If severe hypernatremia (>150), additional water will be added as
needed, but is there ever a time when the body may almost "pop" if
they are incredibly hypernatremic?
Most cases of hypernatremia are associated with a
total body water deficit. If one treats
hypernatremia, by giving water, without sodium, to the patient, there is the
possibility of developing IVV overload, especially if the kidneys do not work
and are unable to excrete urine with the excess sodium and water.
2. Will you please explain the free water deficit?
The free water deficit is the amount of pure water
that must be given to a patient with hypernatremia in order to correct the
hypernatremia. Remember that hypernatremia
means that the ratio of sodium to water is increased. In most cases, as mentioned above, the cause of hypernatremia is
decreased water, not increased sodium.
Calculating the free water deficit is very easy.
Remember that sodium is distributed in ~60% of
total body weight. In other words, a 70
kg individual has sodium distributed in ~0.6 * 70, i.e., 42L, of body
fluid. If this person’Äôs serum sodium
concentration is 160 mEq/L, then their total body amount of sodium is 42L * 160
mEq/L or 6720 mEq. If you want the
serum sodium to actually be 140 mEq, then divide the total amount of body sodium,
6720 mEq, by the desired concentration, 140 mEq/L, to find that this individual
needs to have sodium distributed in 48L of water. Since we already calculated that they had 42L of body fluid,
their deficit is 48L minus 42L, or 6L.
Do we have to calculate with this formula on the exam? (p.4 of Na d/o
lecture) Thank you
David Weiner, M.D.
Posted Apr 18 7:04 AM by medical student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.Do damaged cells (rhabdomyolysis) only take up water and no salt therefore
hypernatremia?
2.With nephrogenic DI, does one have the ability to make ADH, but they can't
use it so they are hyypernatremic? It is a problem with the kidneys rather that
with the central (brain)?
David Weiner, M.D.
Posted Apr 17 11:14 PM by STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
WITH POTASSIUM D/O, IS THE QRS COMPLEX THE MOST SENSITIVE TO VENT. FIB?
2. HOW DOES A DECREASED RATIO OF INTRACELLULAR POTASSIUM TO EXTRAC K CAUSE
DEPOLARIZATION? (WITH HYPERKALEMIA)
3. IS THE WIDER QRS COMPLES WITH HYPERKALEMIA DUE TO A DECREASE IN CALCIUM?
THANK YOU
David Weiner, M.D.
Posted Apr 17 10:44 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
On page 3 of the Na d/o lecture, it states "hypovolemic hyponatremia
occurs when volume depletion is so severe that ADH release is stimulated due to
baroreceptor stimulation." Why is one HYPOVOLEMIC if ADH is stimulated?
-
The teleologic benefit of stimulating ADH release
in hypovolemia is to minimize further water loss, thereby maximizing recovery. In some cases the hypovolemia is so severe
that it persists even after ADH release is maximally stimulated. An example would be the person with persistent
nausea, vomiting and diarrhea that is bed-bound and unable to take in
fluids. Even if ADH were to be
maximally stimulated, if they continue to lose fluids through the vomiting and
the diarrhea, inhibiting urinary water losses will not be sufficient to recover
from the IVV depletion.
David Weiner, M.D.
Posted Apr 17 10:43 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1. on page 2 of the sodium d/o lecture, what are examples of the graph
showing 15% decrease in vol/pressure?
-
Persistent vomiting and/or diarrhea, severe
bleeding, massive heart attack, and peripheral vasodilatation that can occur in
response to a severe bacterial infection (sepsis) are just a few examples.
2. Regarding the cause of sodium being the same and water increasing, you
said that the body may not be able to make dilute urine and that the process
occurs in the distal convoluted tubule? could you please explain?
-
In order to recover from hyponatremia the kidney
must be able to make urine that has a lower sodium concentration than is
present in the blood. This will effect
a greater decrease in total body water than total body sodium. As a result, the ratio of sodium to
water will increase, and the hyponatremia, which remember is a measure of the
ratio of sodium to water, will begin to recover.
-
The only region of the kidney that can make urine
with a lower sodium concentration than is present in the blood is the distal
convoluted tubule. This occurs because
the distal convoluted tubule can reabsorb NaCl, via a NaCl cotransporter, but
does not reabsorb water.
Also, what did you say about diuretics blocking it?
thank you
David Weiner, M.D.
Posted Apr 17 8:52 PM by STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
IS THERE MORE CREATINE IN THE SERUM WHEN 1/2 OF KIDNEY FUNCTION IS LEFT
BECAUSE LESS BLOOD GOES TO THE KIDNEYS TO PEE OUT THE CREATININE? THEREFORE, IT
DOUBLES?
-
When half of the kidney function is left, the
amount of blood whose creatinine is removed decreases by one-half. In order for the rate of creatinine excretion
to equal the rate of creatinine production, the concentration must
double. When the concentration
increases by an amount inversely proportional to the relative decrease in the amount
of blood whose creatinine is removed, the net amount removed will remain
constant.
-
This works, and creatinine is such a useful marker
of renal function, because creatinine is filtered ~100% by the glomerulus and
has little transporter by the remainder of the nephron.
Thus, the kidney’s removal of creatinine is
a fairly accurate measure of the glomerular filtration rate.
David Weiner, M.D.
Posted Apr 17 8:51 PM by MEDICAL STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
IS ONE'S URINE CONCENTRATED IN ACUTE GLOMERULONEPHRITIS? YOU MENTIONED THAT
IT IS NOT IN ATN AND AIN, BUT I DID NOT KNOW IF AID WAS THE SAME THING AS ACUTE
GLOMERULONEPHRITIS BECAUSE THE NOTES (P.3 OF 1ST LECTURE) SAY THAT THE URINE IS
CONCENTRATED WITH ACUTE GLOMERULONEPHRITIS? THANKS
The urine is frequently concentrated in acute
glomerulonephritis, but not always. In
brief, there is a decrease in the amount of NaCl and water filtered because of the
glomerular disease, but the tubules are relatively normal. The tubules ’Äúsense’Äù the decreased amount of
filtered NaCl and water, and interpret this to indicate that IVV is decreased. They then respond by increasing reabsorption
of NaCl and water in an attempt to increase IVV volume. This causes a concentrated urine that is
decreased in volume.
David Weiner, M.D.
Posted Apr 17 8:49 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
In another Q/A answer from MEDICAL STUDENT posted on april 3, there was a
question about NSAIDS causeing prenal azotemia. Why did you not mention that
this can occur with nephritic syndrome, as you mentioned nephrotic?
NSAIDS can cause prerenal azotemia if given in
either nephritic or nephrotic conditions.
Thank you.
2. Also, in an explanation posted on april 3 about BUN measurements, why did
you say , As a result, in volume depleted states the renal reabsorption of urea
is increased, renal excretion is increased.." Why is the renal excretion
increased and not decreased?
You’Äôre right, I should have said that the renal
reabsorption of urea is increased and that the renal excretion is, therefore,
decreased. Thank you for pointing this
out.
Thank you
David Weiner, M.D.
Posted Apr 17 8:46 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
If one blocks angiotensin 2 formation, there is less hydrostatic pressure
and blood goes right through the kidney, as if it wasn't there? So does the
blood not even get into afferenct arterioles? Does it go to the efferent
arterioles?
When Angiotensin II formation is blocked there is preferential
dilatation of the efferent arteriole.
This decreases the hydrostatic pressure in the glomerulus. As a result, the glomerular filtration
decreases. Also, because the efferent
arteriole is dilated, the resistance of blood flow through the glomerulus
increases. Because almost all renal
perfusion initially goes through the glomeruli, before proceeding to the renal
capillaries, the renal perfusion rate increases.
Note that Angiotensin II does not constrict the
efferent artiole to any significant extent under normal conditions. As a result, it is safe to use medications
that inhibit Angiotensin II formation (ACE-I’Äôs) or its action (Angiotensin receptor
blockers, ARB’Äôs) in most individuals.
Angiotensin II becomes important only when there is decreased renal
perfusion, as occurs in IVV depletion or renal artery stenosis. In these cases one must be careful about
using ACE-I’Äôs and ARB’Äôs.
David Weiner, M.D.
Posted Apr 13, 2000 7:58 PM by Student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1. I don't understand why damaged tubules allow water to leak out (decreasing urine volume), but at the same time, don't
allow for reabsorption of Na (thus, increasing Na excretion). Could you please explain this?
-
When tubules are damaged two mechanisms contribute to the "back-leak" of filtered fluid ("early urine"). First, some
of the necrotic cells aggregate in the tubule lumen (interior), obstructing urine flow. Second, areas of the tubule now
exist where cells are no longer present on the basement membrane. These areas allow for filtered fluid to "leak back"
into the renal interstitium, where the fluid is then absorbed into the renal capillaries and returned to the systemic
circulation through the renal veins.
-
In these areas, the fluid that "back-leaks" and is reabsorbed has both Na and water, and they are present in the same
proportion as they are present in the luminal fluid. This fluid also has creatinine in the same concentration as is present
in the luminal fluid. In one sense you are correct, there is reabsorption of Na as a result of this back-leak. In another
sense, however, there is not "specific" reabsorption of Na. This would require intact tubules that have intact Na
transport processes that would allow sodium but not water reabsorption.
-
Because the reabsorption of filtered sodium through "back-leak" parallels the reabsorption of creatinine the net effect
is no different than if the fluid had not been filtered at the glomerulus. As a result, the fractional excretion of sodium
(FeNa) is not altered by the back-leak.
-
Instead, remember that the FeNa would be 100% if the reabsorption of filtered sodium did not exceed the reabsorption
of creatinine. Under normal conditions the reabsorption of filtered creatinine is zero. Under volume-depleted
conditions there is stimulation of sodium reabsorption and the FeNa is very low, less than 1%. However, when
tubules are damaged, they are not able to reabsorb Na (independent of creatinine) maximally, and the FeNa will be
high, generally greater than 3%.
2. On bottom of p. 3 in the Sodium Disorders lecture, non-oliguric ATN is listed as a cause of hypernatrmia. I am
confused bc I thought we said that more Na is excreted with ATN (see above question). Does the specification
"non-oliguric" here make the difference? If yes, could you please explain how/why?
-
With non-oliguric ATN the urine normally contains about half the sodium concentration as is present in the blood. As
a result there is relatively more loss of water than sodium in the urine. This can cause hypernatremia, due to a greater
proportional decrease in the amount of plasma water than plasma sodium. Remember that hypernatremia refers to an
increase in the concentration, not amount, of plasma sodium.
3. CV disease is the most common cause of death in pts suffering from ESRD. Is this because epi levels remain high and
cause HTN, cardiac arrhtyhmias, MI, and stroke EVEN WITH the four interventions we talked about? Why don't we
give some drugs to moderate the high epi?
-
The factors which cause the high rate of cardiovascular disease in ESRD are numerous. These include abnormalities
in lipid metabolism resulting in high total cholesterol, LDL-cholesterol and triglycerides in many patients, elevated
levels of homecysteine, abnormal rates of oxygen free radical formation and abnormal production of platelet
activators. Despite almost forty years of dialysis we still have not identified all the factors.
Once again, thank you for setting up this question/answer website.
David Weiner, M.D.
Posted Apr 13, 2000 7:33 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
On page 3 of chronic renal failure, what does GI RBC loss have to do with renal failure? thanks
-
Renal failure can impair normal platelet clotting activity. This can then lead to an increase in GI RBC loss.
-
You may notice that in the previous question I explained that there is abnormal activation of platelet clotting in ESRD.
One of the problems in ESRD is that patients experience both increased platelet-dependent clotting and increased
bleeding due to impaired platelet-dependent clotting. The exact disturbance appears to be time- and place-dependent.
David Weiner, M.D.
Posted Apr 13, 2000 7:32 PM by medical student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
Regarding acute renal failure, you said that the kidneys are larger due to inflammation. But if the acute renal failure is due
to ATN, the size is normal because of the acute loss in depth of tubules. 1. Do the kidney tubules return to normal size
after the ATN and acute renal failure is over or are they forever necrosed?
-
The kidneys are able to recover almost completely following acute renal failure, whether due to inflammation or to
ATN. However, if the degree of tubular necrosis is too great or if the inflammation is too severe or lasts too long then
the damage may be irreversible. In general, the less severe the initial "insult" to the kidneys and the healthier the
patient the more likely that the kidneys will recover.
2. So, if ATN causes acute renal failure, does that somewhat mean the if the ATN leads to acute renal failure, that is
better than it leading to ESRD?
-
In general, ATN is better than ESRD because it may recover. However, not all cases of ATN recover, leading to
ESRD in some patients.
thank you for explaining
David Weiner, M.D.
Posted Apr 13, 2000 7:29 PM by medical student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
When discussing the physical exam of chronic renal dx, you said if there are signg of IVV, that means something. Isn't
IVV a sign of acute renal failure? Could you please embellish on?
David Weiner, M.D.
Posted Apr 13, 2000 7:28 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
What is the difference between ESRD and chronic renal failure?
-
I use the terms ESRD and "chronic renal failure" interchangeably to indicate the need for renal replacement therapy,
either dialysis or a kidney transplant to allow continued life. The term "chronic renal insufficiency" generally refers to
chronically impaired renal function, but not sufficiently severe to require renal replacement therapy.
b. In the chronic renal failure lecture, where you discussing chronic or SDRD for the average life expectancy being
decreased by 50%?
c. What is the reason why blood pressure control is so essential for tx of chronic renal insufficiency? Thank you.
-
In the presence of renal insufficiency there is a component of afferent arteriolar dilatation and efferent arteriolar
vasoconstriction. This results in increased glomerular capillary pressure, which in the short-term transiently increases
glomerular filtration. However the increased glomerular pressure exposes the glomerular cells, endothelial, epithelial
and mesangial, to localized hypertension which leads over time to glomerular disease which mimics focal
glomerulosclerosis. Proteinuria develops, and proteinuria can be toxic to renal tubules. The net effect is that any
degree of systemic hypertension is magnified in the glomerulus and can precipitate worsening of the renal
insufficiency.
David Weiner, M.D.
Posted Apr 13, 2000 7:25 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
Will you please explain Acute nephritic syndrome? Thank you
-
The acute nephritic syndrome is the clinical manifestation of an acute inflammatory glomerulonephritis. Hematuria is
present, frequently with crenated RBC and occasionally with RBC casts. Proteinuria may be present, but is generally
non-nephrotic (<3.5 gm/d) in magnitude. Hypertension is frequently present. Volume overload may be present, due
to both decreased glomerular filtration and to stimulation of tubular sodium reabsorption.
David Weiner, M.D.
Posted Apr 12, 2000 7:35 PM by medical student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1)If there are huge holes in the glomerulus, is that nephritic syndrome?
2)Is hematuria a sign of nephritis specifically, or can one have it with nephrotic also?
3) Is IgA nephropathy inflammation? Thanks
-
Yes, IgA nephropathy is a form of renal inflammation. The inflammation is predominantly located in the renal
mesangium. IgA is the predominant immunoglobulin present. Hence, the name IgA nephropathy. Next year you may
also hear the term "Berger's disease." Berger was the first person to describe this condition. Some will "honor" him
by using his name to refer to this condition.
David Weiner, M.D.
Posted Apr 12, 2000 7:33 PM by medical student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
Why do hypertensive patients get acute nephritic syndrome?
-
I think (hope) you meant to ask why do patients with the nephritic syndrome develop hypertension. This frequently
occurs, the converse does not.
-
The acute nephritic syndrome (nephritis) is generally an acute inflammatory condition that attacks the glomerular
capillary endothelium and glomerular basement membrane. Because these structures have some similarities to vascular
endothelium and basement membranes in other tissue beds it is not unusual to get generalized arterial vasoconstriction
in acute nephritis.
-
In addition, the acute inflammation of the glomerulus frequently leads to an acute decrease in the filtration of
individual glomeruli. The tubule cells downstream from these affected glomeruli "sense" the decreased filtration and,
incorrectly, interpret the decreased filtration as evidence of intravascular volume depletion leading to impaired
glomerular filtration. They respond by increasing sodium and water reabsorption in order to expand the intravascular
volume. Obviously, this is inappropriate, and, if excessive, will lead to intravascular volume overload which will
contribute to hypertension.
-
Nobody said the kidney was perfect.
2. Would you say that the lesser of the two evils is to have nephrotic instead of nephritic because that doesn't lead to a
chronic d/o?
David Weiner, M.D.
Posted Apr 12, 2000 7:32 PM by students
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.On page 2 of your glomerular d/o lecture, you discussed hypoalbuminemia at the top paragraph. Will you please explain
the mass-balance, why that is incorrect, and what the theory is so far?
-
Most people generally assume that patients with proteinuria develop hypoalbuminemia because urinary albumin losses
exceed the albumin synthetic capacity. Where maximal stimulation to occur the liver could easily maintain normal
albumin levels by matching albumin synthesis to urinary albumin losses. However, this does not occur. Instead, there
is sub-maximal stimulation of hepatic albumin synthesis. One mechanism is that the decrease in oncotic pressure that
occurs as a result of the urinary albumin losses inhibits hepatic albumin synthesis. Another is that inflammation, in
general, can suppress hepatic albumin synthesis.
Thank you
2.Is IgA nephropathy considered both nephrotic and nephritis because
it has hematuria also?
-
IgA nephropathy is generally considered a glomerulonephritis because it generally presents with hematuria, either
macroscopic (visible with the "naked" eye) or microscopic (visible only with a microscopic or a urine "dip-stick").
However, it sometimes presents with proteinuria.
The same with membranoproliferative?
3. Is membranoproliferative a secondary dz and IgA is a primary?
-
Membranoproliferative glomerulonephritis can be either primary or secondary. The same is true to IgA nephropathy.
There are more known causes of membranoproliferative glomerulonephritis (i.e., hepatitis B and hepatitis C) than there
are known causes of IgA nephropathy (i.e., chronic liver disease).
-
Remember, "secondary" only means that we have identified a "more basic" cause of the disease, and "primary" means
that we have not.
David Weiner, M.D.
Posted Apr 12, 2000 7:29 PM by students
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
In the glomerular d/o lecture, you said that there are 3 basic sizes: 1. water and ions, 2. proteins, and 3. proteinuria???.
Could you please tell us the third one?
2)Should proteins not even be filtered by the normal proximal tubule, but just pass right through to the efferent arteriole?
3)Is the number one cause on nephrotic syndrome in adults total (including diab and nondiab) diabetic nephropathy or
membranous nephropathy?
-
Diabetic nephropathy substantially exceeds membranous nephropathy as a cause of nephrotic syndrome if one includes
both diabetics and non-diabetic patients. However, in non-diabetic patients membranous nephropathy is the
predominant cause of nephrotic syndrome. Remember, focal segmental glomerulosclerosis (FSGS) exceeds
membranous nephropathy in African-Americans. Why the difference is unknown.
David Weiner, M.D.
Posted Apr 11, 2000 11:55 PM by Jennifer Goldman
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
I just posted a question about SIADH and fluid volume. I forgot to ask one other question. If a person is "euvolemic" in
SIADH (which I don't totally uderstand in itself), don't you cause other problems by restricting their water intake?
David Weiner, M.D.
Posted Apr 11, 2000 11:36 PM by Jennifer Goldman
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1) On p. 3 of the Chronic Renal Failure lecture, you wrote that there are increased rates of basal gi rbc loss with ESRD.
Can you expand on this-- why is there increased gi rbc loss?
2)Some protein normally gets filtered, but then it is reabsorbed in the proximal tubule. Is proteinuria nephrotoxic because
the normal mechanism of uptake (of filtered proteins by the proximal tubule) is overwhelmed? Does the stress on the
system cause more damage?
3)On top of p.2 of the Glomerular Disorders lecture, you wrote that there is hypoalbuminemia but you also commented
on albumin synthesis. I am confused. The liver can make more than 25g of albumin each day, exceeding albumin loss, but
does the liver just not do what it is capable of doing (resulting in hypoalbuminemia)?
Before your lecture, I thought that the liver couldn't make enough albumin to compensate for the loss, and it just made
more lipoproteins instead. Could you please explain what exactly is going on?
-
One mechanism is that the decrease in oncotic pressure that occurs from the the urinary albumin losses inhibits hepatic
albumin synthesis. Another is that inflammation, in general, suppresses hepatic albumin synthesis.
4)I thought that ADH increased the body's water volume, but how can people with SIADH be euvolemic? Thank you
very much for answering these questions.
-
The increased amounts of ADH slightly increase total body water, but the amount is undetectable by physical
examination. However, it is sufficient to increase intravascular volume sufficiently to cause a slight inhibition of
sodium reabsorption by renal tubules. This results in increased urinary sodium excretion and a decrease in total body
sodium content. The net effect is a slight increase in total body water and a simultaneous decrease in total body
sodium, resulting in a larger, and easily measured, decrease in sodium concentration (the ratio of sodium to water).
David Weiner, M.D.
Posted Apr 11, 2000 1:46 PM by STUDENT
In Reference to http://medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
WILL YOU PLEASE EXPLAIN HOW GIVING EXTRA CALCIUM TREATS HYPERCALCEMIA? YOU SAID
THAT IF YOU DECREASE THE CALCIUM INSIDE THE CELL, THAT ALSO WORKS, BUT IS HARD TO
DO???? THANK YOU
-
Giving calcium is effective for treating the cardiac manifestations of hyperkalemia, not hypercalcemia.
-
The cardiac manifestations of hyperkalemia are due to inhibition of calcium entry during the action potential. Calcium
entry is regulated partially by membrane potential. Hyperkalemia decreases (makes less negative) membrane potential,
thereby decreasing calcium entry. Giving a bolus of intravenous calcium increases, transiently, extracellular calcium,
which can "compensate" for the decreased membrane potential, and thus increase the rate of calcium entry back
towards normal.
-
If a method existed to decrease intracellular calcium, then this too might be able to return the rate of calcium entry
back to normal in hyperkalemia.
David Weiner, M.D.
Posted Apr 11, 2000 1:45 PM by student
In Reference to http://medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
How does glucose in diabetic patients lead to hyperkalemia?
-
Glucose, if insulin is not present, causes a localized increase in extracellular osmolality. The increase in extracellular
osmolality, in the absence of an increase in intracellular osmolality, causes a redistribution of potassium from the
intracellular to the extracellular compartments. The result is hyperkalemia.
-
If insulin is present, then there is a parallel increase in both intracellular and extracellular osmolality, and there is no
redistribution of potassium.
David Weiner, M.D.
Posted Apr 11, 2000 1:44 PM by student
In Reference to http://medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
a. With hyperkalemia, there is a change in the ratio from extracellular to intracellular. Why isn't there also an increase in
intracellular potassium by diffusion down its concentration gradient?
-
There is. However, the maximum intracellular potassium concentration is limited to ~145 mEq/L. Any higher would
require an increase in osmolality to >290 mOsm/kg (each potassium molecule must be balanced with an anion, thus
contributing two molecules to osmolality). Since the basal intracellular potassium concentration is ~120 mEq/L, the
relative (proportional) increase in intracellular potassium concentration is less than 25%. As a result, changes in
intracellular potassium are not very effective at counter-balancing increases in extracellular potassium.
b.In hypokalemia, p. 3 of notes states, hypokalemia cause hypertension, because of the stimulation of sodium
retention and extracelularl volume expansion. Why does this occur?
-
The exact mechanisms are not completely understood.
-
Our best guess for the sodium retention is as follows. Hypokalemia increases the expression of a proton-potassium
exchanging ATPase (H-K-ATPase) in the apical membrane of collecting duct intercalated cells. Under normal
conditions this protein exchanges intracellular protons for luminal (urinary) potassium. The net effect is reabsorb
potassium and thus minimize urinary potassium loss.
-
However, sodium can sometimes bind to and be transported by the potassium-binding site. In hypokalemia, there is
both an increased amount of this protein and there is less filtered potassium. As a result, sodium molecules are more
likely to bind to and be reabsorbed by this protein. This leads to increased sodium reabsorption and increased sodium
retention.
David Weiner, M.D.
Posted Apr 11, 2000 1:41 PM by student
In Reference to http://medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
In the potassium d/o lecture, figure 2 shows EKGs. What is auricular standstill IV block and how is that associated with
this lecture?
What about the high U wave?
Why is ventricular fibrillation occur with both hypo and hyperkalemia? Is one more prone to it if hypo?
-
Hyperkalemia directly causes ventricular fibrillation. Intravenous potassium is one of the chemicals used the death
penalty.
-
Hypokalemia does not cause ventricular fibrillation, but makes you more susceptible to develop it. Hypokalemia also
makes it more likely that if you have an abnormal ventricular activity (premature ventricular contraction, PVC) it will
"turn into" ventricular fibrillation. However, if there is no abnormal electrical
activity then ventricular fibrillation
will not occur in hypokalemia.
David Weiner, M.D.
Posted Apr 11, 2000 1:37 PM by student
In Reference to http://medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1.What actually has to happen to see intravascular volume depletion?
|
There has to be sufficient loss of intravascular volume to detect the change on physical examination. Examples of
physical examination findings to look for are: |
2.How does one treat chronic hyponatremia?
-
First, treat the underlying cause, if possible. If volume depletion is present, then correct the volume depletion. If
cardiac dysfunction, liver dysfunction or the nephrotic syndrome is present, then treat these underlying conditions. If
nausea, vomiting or pain are present, then treat these conditions.
-
Second, if the patient is either "euvolemic" or "volume overloaded," then fluid restriction will be beneficial. As the
total amount of body water decreases in response to decreased water intake, there is a slight decrease in intravascular
volume. The kidney's first response to intravascular volume depletion is to increase sodium reabsorption and
retention. This results in the slow correction of the hyponatremia by increasing the ratio of sodium to water.
3.The sentence about sodium disorders, "hypervolemic hyponatremia most commonly occurs when the body senses a
decreased EABV, despite total body fluid overload, that may be massive." Is this a good thing with CHF though?
-
Unfortunately not. Although short-term increases in intravascular volume can increase cardiac pre-load and can
increase cardiac output, the long-term effect is to increase ventricular dilatation, which results in impaired myofibril
contraction and a decreased cardiac output. Long-term there is also the development of pulmonary edema, in addition
to peripheral edema. The net is that chronic increases in total body volume are not beneficial in CHF, and can be
detrimental.
David Weiner, M.D.
Posted Apr 4, 2000 7:20 PM by STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
With decreased EABV and with one who is hypervolemic with hyponatremia, with nephrotic syndrome, why wouldn't this be
with renal failure with the "unable to excrete water with renal failure?"
-
Renal failure is defined, rather arbitrarily, as impaired glomerular filtration. As a result, the individual with decreased
EABV and hypervolemic hyponatremia but with normal or near normal glomerular filtration would not be considered to
have "renal failure."
David Weiner, M.D.
Posted Apr 4, 2000 7:17 PM by STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
CAUSE #3, WITH NA DISORDERS, UNDER LIVER DISEASE, YOU MENTIONED LEFT TO RIGHT SHUNTING.
WILL YOU EXPLAIN HOW THAT AFFECTS THE EFFECTIVE ARTERIAL BLOOD VOLUME?Ý
-
This is a good question and one that has confused physicians for a long time. For some reason, the left-to-right shunting
that occurs frequently in liver disease causes the systemic pressure and volume sensors to believe that arterial blood
volume is decreased. Quite frankly, the exact mechanism through which this occurs remains controversial and
incompletely understood.
ON P.2 OF NA D/O HANDOUT, THERE IS A FIGURE #1. IN CLASS, YOU DID NOT SHOW AND EXAMPLE OR
DISCUSS THE 15% INCREASE IN VOL/PRESSURE? WHAT DOES THIS REPRESENT? WHAT IS THE
IMPORTANCE OF IT?
-
When one is volume overloaded and/or hypertensive ADH release is inhibited. This results in increased urine volume and
correction of the volume overload and/or hypertension, if unopposed by the initiating factors that created the volume
overload and/or hypertension. The net result would be a tendency to have a slightly higher serum sodium in these cases.
SEMANTICALLY, HOW CAN ONE BE "EUVOLEMIC, BUT HAVE INCREASED WATER?
-
One is "euvolemic" when physical examination does not detect evidence of either volume overload (peripheral edema,
pulmonary edema, hepatojugular reflux, S3, elevated jugular venous pressure, etc.) or volume depletion (orthostatic
hypotension, dry mucous membranes, decreased jugular venous pressure, skin tenting, etc.). However, these are
somewhat inexact and insensitive measures. As a result, one can have excess total body water in an amount that is
sufficient to cause hyponatremia but is not sufficient to be detectable by physical examination.
David Weiner, M.D.
Posted Apr 4, 2000 7:14 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
Regarding the extracellular sodium concentration and the total body sodium content, which one is used to diagnoses
hypernatremia and hyponatremia?
What are the uses of knowing each?
-
Conceptually it is important to differentiate between sodium concentration and sodium content because of their
implications for treatment. If one confuses hyponatremia with decreased sodium content, then one is tempted to treat
hyponatremia with sodium administration. Instead, most cases of hyponatremia are associated with total body sodium
excess. The decreased plasma sodium concentration reflects a total body water excess that is proportionally greater than
the sodium excess. In this case, the correct treatment is to correct the underlying cause that is causing the water retention.
It is also necessary to limit all water that the patient is give, because any further water, whether through the diet or through
medications, will exacerbate the hyponatremia.
Could you please explain the definition of the effective arterial blood volume?
-
Effective arterial blood volume (EABV) is an admittedly nebulous term that tries to explain why sometimes the body
and the kidneys appear to believe that the individual is hypovolemic despite the presence of substantial total body volume
overload (edema, elevated JVP, etc.). To explain this, we attempt to say that the "effective amount of arterial blood
volume" is decreased. In doing so, we are implying that the volume of the arterial blood compartment can be
differentiated from the venous and the extravascular blood volume. At present, one cannot measure the EABV, and the
term is used more descriptively to explain renal fluid retention despite total body volume overload.
David Weiner, M.D.
Posted Apr 4, 2000 7:05 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
What is the long term effect on the brain of long term hyponatremia? not cell swelling?
-
Long term, or chronic, hyponatremia allows the return of brain cell size back to normal. It is generally believed that
chronic hyponatremia is detrimental. This is because patients with chronic hyponatremia have a shorter life expectancy.
My concern is that the shortened life expectancy may be due to the underlying disease that caused the chronic
hyponatremia, and not due to the hyponatremia itself. Nevertheless, most physicians will try to treat chronic
hyponatremia. Because the problem in most cases is related to excess total body water, an important component of the
therapy of chronic hyponatremia is fluid restriction. This is difficult for most patients to comply with, and success rates
are low. On the horizon we can see ADH antagonists that will block the increased ADH levels that cause the renal water
retention in this condition.
David Weiner, M.D.
Posted Apr 3, 2000 7:00 PM by MEDICAL STUDENT
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1. HOW DO NSAIDS CAUSE PRERENAL AZOTEMIA?
-
Prostaglandins play a central role in the autoregulation of renal perfusion in "low-flow" states such as hypotension and
hypovolemia. NSAIDs can cause acute renal failure by interfering with prostaglandin production. As a result, renal
perfusion decreases and, consequently, glomerular filtration decreases. The renal tubules can only "sense" that glomerular
filtration is decreased, and they interpret this to mean that the individual is either hypotensive or hypovolemic. Renal
tubules then try to correct this abnormality by reabsorbing sodium and water maximally, resulting in a picture of pre-renal
azotemia.
-
This only occurs in conditions where prostaglandins are necessary to maintain renal perfusion, such as hypotension,
hypovolemia or decreased effective arterial blood volume, as occurs with congestive heart failure, liver disease and
nephrotic syndrome. If you have none of these conditions then NSAIDs are safe and will generally not cause acute renal
failure.
2. WHY DOES ONE HAVE A CONCENTRATED URINE IN PARENCHYMAL ARF?
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Concentrating the urine requires intact tubular function in order to reabsorb sodium and water, thereby concentrating the
urine. When the renal tubules are damaged, as occurs in ATN (acute tubular necrosis) and in AIN (acute interstitial
nephritis) they are unable to concentrate the urine.
3. IS RPGN PERMANENT DAMAGE IF ONE DOES NOT DIE?
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The damage will be permanent if it persists too long before treatment is begun. If treatment is begun early enough, while
inflammation but not fibrosis, is present then it frequently is reversible. The key features for determining the patient's
prognosis for recovery of renal function is the amount of irreversible scar tissue that is present (irreversible) and the
amount of tissue with active inflammatory disease (reversible)
4. wHY CAN'T THE feNA BE USED IN THE NONOLIGURIC PATIENT?
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The FeNA is used to determine whether the tubules are maximally concentrating the urine and maximally reabsorbing
filtered sodium in an attempt to correct intravascular volume depletion. If the kidney is responding appropriately to
intravascular volume depletion, then urine volume should be minimal (<500 ml/d). If the urine volume is not less than
500 ml/d, then the kidneys are unable to respond to intravascular volume depletion. For example, geriatric kidneys take
longer to respond to hypovolemia, and they take longer to decrease urine volume and urinary sodium excretion.
Alternatively, diuretics increase urine sodium excretion, thereby increasing urine volume. As a result, if one is
nonoliguric, a high FeNA cannot differentiate between ATN with tubular dysfunction, diuretic administration that is
inhibiting tubular function, or age, which is slowing the tubular response to volume depletion. This results in a lack of
usefulness of the FeNA in nonoliguric conditions.
David Weiner, M.D.
Posted Apr 3, 2000 6:52 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
1)In your "grandma" example on 4/3/2000, were you considering her to be in good health and not malnourished and cachectic
so the formular #1 can apply?
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Yes, I was. We all lose muscle mass as we age. Small, thin elderly individuals, especially women, are common, and are
not necessarily malnourished or cachectic.
2)What is the cut off and weight of a diagnosis for BUN measurements to assess kidney fxn?
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The BUN can be used to measure renal function in a fashion similar to that used for creatinine. The limitation is that BUN
is affected by catabolism (increases urea formation), as can occur either with gastrointestinal bleeding (catabolism of RBC
in the GI tract) or with steroids. In addition, the renal tubules reabsorb urea in the process of concentrating the urine. As a
result, in volume depleted states the renal reabsorption of urea is increased, renal excretion is increased, whereas there is
no change in the renal reabsorption and net excretion of creatinine. The effect is that the ratio of plasma BUN to Cr
increases from the normal 10:1 to ~20:1.
3)How does hypocalcemia occur with chronic renal failure?
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A major determinant of serum calcium is GI tract absorption of dietary calcium. This is regulated to a large extent by
1,25-dihydroxy-vitamin D3. The kidneys are responsible for the final step in 1,25-dihydroxy-vitamin D3 metabolism,
namely 1-alpha-hydroxylation of 25-hydroxy-vitamin D3. As a result, serum 1,25-dihydroxy-vitamin D3 levels are low in
individuals with chronic renal failure. This causes decreased GI tract calcium absorption and hypocalcemia.
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This explains why individuals with hyperparathyroidism develop hypercalcemia if they have normal renal function, but not
if they have renal failure. The hypercalcemia results from PTH stimulating the renal conversion of 1-alpha-hydroxy-vitamin D3 to 1,25-dihydroxy-vitamin D3. The increased 1,25-dihydroxy-vitamin D3 level then increases GI tract calcium
absorption, leading to hypercalcemia. In patients with renal failure, in whom hyperparathyroidism is almost the rule, the
kidneys are unable to form 1,25-dihydroxy-vitamin D3, and, consequently, there is no stimulation of GI tract calcium
absorption and no development of hypercalcemia.
David Weiner, M.D.
Posted Apr 3, 2000 6:50 PM by student
In Reference to http://www.medinfo.ufl.edu/year2/clinmed/Nephrology/Index.htm
In the lecture on acute renal failure, could you please answer the following questions?
1. On the first page, it is typed, under most "short-term" cases, the rate of creatinine production is relatively constant. Could
you give us some examples of short-term causes? i.e. exercise???
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The rate of creatinine production is relatively unchanged in almost all cases in time frames of 1-2 months. As a result,
changes in the serum creatinine concentration almost exclusively reflect changes in the rate of renal excretion.
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There are a few cases, however, in which creatinine production would not be constant. Creatinine results from the non-ezymatic conversion of creatine, which comes from muscle. Diseases that cause rapid skeletal muscle death, termed
rhabdomyolysis, cause increased rates of creatine release and subsequently increased rates of creatinine production.
Similarly, increased oral ingestion of creatine as a nutritional supplement can increase the rate of creatinine production.
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Examples of causes of rhabdomyolysis include having a building fall on you in an earthquake, prolonged seizure activity,
being comatose in a position that results in excessive pressure over a large muscle group such that arterial perfusion is
impaired and exhaustive exercise in the heat, as occasionally occurs to armed forces recruits during 'basic training.'
2. What are some examples of a "stopper" of the kitchen sink model?
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Bilateral kidney removal for renal cell cancer, acute tubular necrosis from nephrotoxic medications, bladder outlet
obstruction that results in the prolonged inability to urinate, diabetic nephropathy, etc.
3.You said that serum Cr is what is measured to determine renal function, that is, it is plugged into the equation for GFR.
But, the serum Cr lags behind changes in renal function. is there anything we can measure to get an accurate assessment of
our patient right away?
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In general, no. An indirect measure is that the creatinine will increase by about 2 mg/dl per day with complete loss of
renal function. Also, if the patient is severely oliguric (<100 ml/day), then it is likely that their glomerular filtration rate is
less than 10 ml/min (normal is ~120 ml/min).
I. David Weiner, M.D. |
