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Medical Forum / General / Laboratory / June 2005

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Questions: Blood level/ Total Body levels?

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lordshiva5753@rediffmail.com - 01 Jun 2005 09:34 GMT
Hello,

Under routine tests, we meausre blood/serum levels of any bio-chemical.
But there can be some difference in understanding on blood/serum level
& total body level. I want to know;

1. What are blood/serum levels & total body levels of bio-chemicals?

2.What can be the difference in understanding an imbalance/disease by
measuring at blood/serum level & whole body level of any biochemical?

3. Can measurements of blood/serum level are sufficient to judge any
disease?

4. Is it possible that inspite of blood levels of biochemicals are
within normal range but still these are imbalanced at total body/other
body sites levels?

5. Whether body stores excess acidity during day time & excrete during
night time? Where body stores excess of acidity or other biochemicals
till it excrete via urine etc?

Can you please tell me about these aspects?
JEDilworth - 01 Jun 2005 18:47 GMT
Are you reading one of those body pH sites too?

How would you propose to measure "body" levels? Stick a probe through
your skin or something? How would YOU measure a body pH? Which fluid
would YOU choose?

Levels of body analytes are always in flux but stay within certain
normal ranges unless there's some disease or trauma interfering.

Medical laboratories measure analytes on serum, urine, and body fluids
(paracentesis, thoracentesis, pleural, knee fluid, spinal fluid, etc. if
these are aspirated and send for analysis). Analyte levels differ
depending on the fluid sent. All fluids have known normal ranges of
analytes sent for testing. The normals for these fluids are not all the
same, but differ by the type of fluid. Which one would you pick for
testing your body level?

Analyte levels don't measure disease per se. They give results which,
combined with a patient's history and symptoms, can lead the doctor into
diagnosing a disease. Sometimes the doc also needs xrays and other scans
to come to a firm diagnosis. Sometimes diagnosis is easy. Sometimes it
takes years to diagnose certain conditions.

http://web2.iadfw.net/uthman/lab_test.html

This is a good page to start on for information regarding common lab
results. Dr. Uthman is a pathologist - a type of physician that does
work both with tissues and is qualified to be the head of a clinical
laboratory. These pages are somewhat technical but full of information.
The tests he talks about are ordered millions of times a day in
laboratories all over the world, and are basic metabolic tests.

What you have asked is that, if your blood work is normal, is your "body
level" (whatever that means) abnormal? These people are just trying to
sell you their STUFF. They're dumbing down body chemistry to sell you
STUFF. Don't be led on.

Judy Dilworth, M.T. (ASCP)
Microbiology

> Hello,
>
> 4. Is it possible that inspite of blood levels of biochemicals are
> within normal range but still these are imbalanced at total body/other
> body sites levels?
Robert - 01 Jun 2005 21:45 GMT
> Hello,
>
[quoted text clipped - 3 lines]
>
> 1. What are blood/serum levels & total body levels of bio-chemicals?

??? Why?
It's more important to eat healthy than to look at any single level.
If you have disease then it is more important to get a diagnosis and deal
with it that way.
It is not important for you or anyone to know how or what the normal
laboratory values are.
There are many differences in serum and total body stores and it is
impossible for somebody not in the health field to understand it.
There are laboratory tests that are measured independent of carrier proteins
which can reflect more the total body stores.
Ionized calcium, ionized magnesium free T4, free dilantin are examples of
that.
Unless you want to have a brain biopsy everytime you want to know brain
stores then you must live with CSF and blood levels.

> 2.What can be the difference in understanding an imbalance/disease by
> measuring at blood/serum level & whole body level of any biochemical?

Analytes can be altered by the carrier proteins and total calcium levels may
be high or low because of the carrier protein and not the actual total
calcium stores. These are usually really sick people with very low albumin
levels in the intensive care rooms. The blood total calcium is low because
the albumin is low. If you do an ionized calcium which is the free form of
the calcium then it is normal.

> 3. Can measurements of blood/serum level are sufficient to judge any
> disease?

Disease usually has a constellation of laboratory findings and not only one
single analyte level. A negative finding is just as signficant as a positive
finding and each is related to a particular disease.
In terms of diagnosis each has a negative predictive factor in terms of
percent and a postive predictive factor.
Doctors know which test are sensitive to detect disease and which tests are
highly specific in diagnosing disease.
They have been doing this for years and years.

> 4. Is it possible that inspite of blood levels of biochemicals are
> within normal range but still these are imbalanced at total body/other
> body sites levels?
It is possible but like I said you look at all tests and the complete
picture of the disease.
Keep in mind that most diagnosis is done with a history. The lab only
confirms that diagnosis. You never diagnose with lab tests alone.

> 5. Whether body stores excess acidity during day time & excrete during
> night time? Where body stores excess of acidity or other biochemicals
> till it excrete via urine etc?

Last I heard people still sleep at night and yes pH changes as a normal part
of life. People also urinate as a normal part of life.

> Can you please tell me about these aspects?
kumar - 02 Jun 2005 06:00 GMT
Judy Dilworth, Robert,

Many thanks for detailed replies. Let us understand Iron. Iron is not
easily excreted in urine or other physiological system except 1mg per
day in sweat etc. If excess or imbalanced, body may trigger its stores
in liver or other sites still keeping blood levels at normal range.
What about other biochemicals? Are all can act alike this or this is
specific to Iron only? In chronic stages can it be possible that in &
out of biochemicals from blood vessels is effected resulting false or
more in or more out of BVs? Do biochemicals are present in
salt/compound form or in Ionic form in tissues other than in blood?

Robert, About acid stored in some tissue(may be epithillum) in day time
& releases ar night time: I read somewhare but lost this link. Is it
there or not? It can be important to know it because there are many
conditions which are related/specific to night or day time as night
excess urination, cortisol etc. Can't some night activities be related
to excess acidity in night time?
Robert - 02 Jun 2005 09:17 GMT
> Judy Dilworth, Robert,
>
> Many thanks for detailed replies. Let us understand Iron. Iron is not
> easily excreted in urine or other physiological system except 1mg per
> day in sweat etc. If excess or imbalanced, body may trigger its stores
> in liver or other sites still keeping blood levels at normal range.

There are a variety of lab tests pertaining to iron. The total iron level,
the total binding capacity of or for iron and ferritin.
There are specific genetic testing for hemochromatosis.
The storage form of iron, ferritin can be elevated or normal in the blood in
the presence of iron deficiency as a result of inflammation. The total iron
level may be reduced in chronic disease. You can have specific target organs
like the liver damaged by alcohol produce local iron overload and an
elevated iron. (MILT) increased MCV,iron,Liver enzymes, triglycerides in
alcohol damage. The reticuloendothelial system keeps the blood iron and
storage pool in constant change.
> What about other biochemicals? Are all can act alike this or this is
> specific to Iron only?
The blood is the transport system to and from storage sites throughout the
body. The exception being the blood brain barrier.

In chronic stages can it be possible that in &
> out of biochemicals from blood vessels is effected resulting false or
> more in or more out of BVs? Do biochemicals are present in
> salt/compound form or in Ionic form in tissues other than in blood?

Ionic forms are dependent on pH or acidity. You have osmosis and active
transport of many chemicals. Blood vessels are not dead but are quite active
metabolically.
One example would be the presence of cholesterol crystals in pseudochylous
effusions or pleural fluid. With chronic disease such as tuberculosis or
rheumatoid arthritis the pleural effusion may be chronic or long standing
and result in a thickened plueral membrane which can not transport the
cholesterol adequatetly resulting in cholesterol crystals in the fluid.
These crystals are important diagnostically. Cholesterol is not normally
found in crystal form so the form is very important.

> Robert, About acid stored in some tissue(may be epithillum) in day time
> & releases ar night time: I read somewhare but lost this link. Is it
> there or not?
You breathe more shallow at night and thus retain more acid along with
reduced oxygen tension and circulation.

It can be important to know it because there are many
> conditions which are related/specific to night or day time as night
> excess urination, cortisol etc. Can't some night activities be related
> to excess acidity in night time?

As you state certain conditions may be worse at night. One such disease is
paroxsymal nocturnal hemoglobinemia in which red cells are destroyed because
of the body changes related to night time.
Some worms can detect these body changes such as microfilaria and come out
from deep in the tissues to the circulating blood in order to time it right
for a mosquito to come along and go for a ride.
kumar - 02 Jun 2005 12:35 GMT
"The blood is the transport system to and from storage sites throughout
the body. The exception being the blood brain barrier."

Robert, thanks again. Can you tell more about these storage sites? I
think bone are for Ca,P,Mg. Which are others? Whether this storage will
be in salt/compound form as in bones?

"Ionic forms are dependent on pH or acidity."

Do you mean pH or acidity can only convert biochemicals in their Ionic
form? I have a serious thought on this; Is it possible that all or most
medicines effects by making changes in acid/base & water(mucus)
balances? Do all or most medicines effects these balances on total
body's levels(because in blood these are in quite narrow range?

"One example would be the presence of cholesterol crystals in
pseudochylous effusions or pleural fluid. With chronic disease such as
tuberculosis or rheumatoid arthritis the pleural effusion may be
chronic or long standing and result in a thickened plueral membrane
which can not transport the cholesterol adequatetly resulting in
cholesterol crystals in the fluid.
These crystals are important diagnostically. Cholesterol is not
normally found in crystal form so the form is very important."

Yes, it is very important. Probably, changes in other membranes can be
very important in understanding many disorders.

"You breathe more shallow at night and thus retain more acid along with
reduced oxygen tension and circulation."

Do you know what is overall body acid levels during day or night? Can
acid be stored in other than blood? If Isoenzymes are related to this
acid levels in specific parts?

"As you state certain conditions may be worse at night. One such
disease is paroxsymal nocturnal hemoglobinemia in which red cells are
destroyed because of the body changes related to night time. Some worms
can detect these body changes such as microfilaria and come out from
deep in the tissues to the circulating blood in order to time it right
for a mosquito to come along and go for a ride."

Good information. Can you tell some more conditions which may  worse or
improve during day or night time or are seasonal?

Regards.
Robert - 02 Jun 2005 20:16 GMT
> "The blood is the transport system to and from storage sites throughout
> the body. The exception being the blood brain barrier."
>
> Robert, thanks again. Can you tell more about these storage sites? I
> think bone are for Ca,P,Mg. Which are others? Whether this storage will
> be in salt/compound form as in bones?
I think you would best be taking a physiology course that would get down to
the basics with that.
Just about any structure can be in equilibrium with it's surrounding.
One of the theories of calcium pyrophosphate crytal disease is the
mobilization of calcium from the cartlidge into the joint space due to low
serum calcium levels.
Salt or ionic forms are dependent on the redox potentionals, hormonal
influences and local physiology such as cytokines and inflammation.

> "Ionic forms are dependent on pH or acidity."
>
> Do you mean pH or acidity can only convert biochemicals in their Ionic
> form? I have a serious thought on this; Is it possible that all or most
> medicines effects by making changes in acid/base & water(mucus)
> balances?
Medicines are impacted by the pH and can be excreted based on pH in some
instances. Some over-dose treatments involve giving base to increase renal
excretion.
Medicines require good circulation and thus good redox potentials. With
tissue damage the redox potential decreases with reduced oxygen and poor
circulation in the damages tissues thus tetanus or other infections are hard
to treat.
Some tissues such as the prostate have very specific pH normals and only
certain  antibiotics can penetrate into the prostate.
You might want to review some pharm dynamics.

Do all or most medicines effects these balances on total
> body's levels(because in blood these are in quite narrow range?
Each drug is dependent on the unique physiology of that drug.
Statins can deplete Coenzyme Q levels and lead to muscle damage. Some TM
medicines can deplete pyridoxine.
Some BP meds can deplete potassium.

>  "One example would be the presence of cholesterol crystals in
> pseudochylous effusions or pleural fluid. With chronic disease such as
[quoted text clipped - 7 lines]
> Yes, it is very important. Probably, changes in other membranes can be
> very important in understanding many disorders.
Membrane permeability is a big research thing right now with the blood brain
barrier drugs.

> "You breathe more shallow at night and thus retain more acid along with
> reduced oxygen tension and circulation."
>
> Do you know what is overall body acid levels during day or night? Can
> acid be stored in other than blood? If Isoenzymes are related to this
> acid levels in specific parts?
Stored acid?
You need to review again your physiology. At the cellular level oxygen is
combined with hydrogen H+ to form water (respiration). Excess H because of
decreased oxygen can be temporarily exchanged with potassium at the red cell
level and thus a high potassium associated with metabolic acidosis.
With hyperventilation a decrease CO2 causes alkalosis with resulting
decrease in ionized calcium and muscle twitching.
Isoenzymes are pH specific and are thus located in tissues that the pH is
appropriate. Alkaline phosphatase is optimal in alkaline pH and acid
phosphatases are optimal in acid mediums. All enzymes are pH dependent via
enzyme kinetics.

> "As you state certain conditions may be worse at night. One such
> disease is paroxsymal nocturnal hemoglobinemia in which red cells are
[quoted text clipped - 5 lines]
> Good information. Can you tell some more conditions which may  worse or
> improve during day or night time or are seasonal?
Not so much in difference in symptoms but in physiology as most as you state
are hormonal catabolic and anabolic cycles, estrogens, and most are
reflected in laboratory parameters although not stated as such in the normal
range.

> Regards.

Good luck and start taking some classes.
kumar - 03 Jun 2005 11:12 GMT
Robert, thanks.

"Isoenzymes are pH specific and are thus located in tissues that the pH
is appropriate"

Let us check LDH isoenzme specific to heart. Can it be effected by
excess lactic acid in cardiac muscles? Can there be excess LA in heart
muscles but still normal in blood, causing heart damage & increase the
cardiac enzymes LDH etc?

Can it be possible that total body level of any bio-chemical is
normal/defficient, but still higher in blood OR lower in blood still
higher in tissues(total body level)? Will this be considered as
store/accumulation OR imbalance OR defficiency of any biochemical?
Blood levels can be indicative of later/emergency stage esp. of
macro-minerals, so we may need to understand levels at other sites also
for early assesment of any condition. Moreover blood levels can be
effected due to disorders in BVs walls for exchange of bio-chemicals.
Is it not so?

Eg; suppose a person with persistant high blood glucose levels can have
it or not, by more tissues-vessels exchange of BG if blood is thin(low
HCT) & if cell walls of BVs favour it(more preamble)--still total body
BG levels are normal (person feels no symptoms even on very high BG
levels) .
Regards.
Manky Badger - 03 Jun 2005 18:03 GMT
> Robert, thanks.
>
[quoted text clipped - 3 lines]
> Let us check LDH isoenzme specific to heart. Can it be effected by
> excess lactic acid in cardiac muscles?

Without wishing to appear rude, why are you asking such a specific question
?
Robert - 03 Jun 2005 18:59 GMT
> > Robert, thanks.
> >
[quoted text clipped - 6 lines]
> Without wishing to appear rude, why are you asking such a specific question
> ?

I am backing out of this and saying that such things are better covered in
a biochem class and not here.
So I apologize to the group. I thought he had a specific question but it
seems as though it is much more extensive.
Manky Badger - 03 Jun 2005 19:07 GMT
>> > Robert, thanks.
>> >
[quoted text clipped - 12 lines]
> So I apologize to the group. I thought he had a specific question but it
> seems as though it is much more extensive.

Which is what prompted me !
kumar - 04 Jun 2005 04:13 GMT
Manky,

"Without wishing to appear rude, why are you asking such a specific
question
?"

I posted following case in other form. I hope it will clear my
intentions.

A diabetic patient on insulin & metformin1000mg, taken many mangos &
some heavy foods on previous days got his cardiac enzymes elevated (LDH
near to higher normal level) CK & troponinI, (g) normal) elevated with
no abnormality in ECG, lipids some elevated, no hypertention, no undue
exertion on stress/walking, some circle is noted on 2D eco(not
confirmed as yet). Can it be thought it can be due to higher lactic
acid due to metformin & eating acidic foods?
Robert - 04 Jun 2005 06:38 GMT
> Manky,
>
[quoted text clipped - 12 lines]
> confirmed as yet). Can it be thought it can be due to higher lactic
> acid due to metformin & eating acidic foods?

We are not doctors here and it has been said by many that we have just
enough knowledge to be dangerous.
Here is a site that mentions precautions.
http://www.diabetesselfmanagement.com/article.cfm?sid=5&tid=34&stid=61&aid=700&s
k=5WZ5


Alcohol can cause LA also in people taking glucophage.
You really didn't mention any symptoms that would be consistent with LA. You
did not mention a lactate level. It is more appropriate to do an arterial
lactate level and not a venous sample.
Some what unclear about the nature of the LDH level and would be interested
to see the LDH1 LDH2 flip normally seen in the heart fraction.. An SGOT or
AST would also shoot up.
Depending on the location of an infarction the total CK may or may not be
elevated. The troponin I and CKMB are time dependent. A BNP would be good to
check for CHF, cirrhosis and nephrosis all of which would be contra
indicated in using glucophage.
If you look at the classic criteria to rule out LA.
[Kruze JA ] are not met which are: severe acidosis with hyperventilation,
blood pH < 7.3, serum lactic acid > 5 mmol/L and large anion gap > 15 meq /
L. Metformin toxicity therefore can be ruled out.
Kruse JA. Metformin associated lactic acidosis. The Journal of Emergency
Medicine. 2001;20(3):267-272.

This medicine is contraindicated in people with lung function problems
indicating ventilation is important in handling the normal acid load. This
would imply that all acid loads may be of concern. The creatinine is
important in judging renal excretion obviously.
The older the patient is the higher the chance of developing LA.
and you mention no age of that patient.
If the lipid panel is apparently normal you might want to expand the
coronary risk panel if confirmed AMI and you make no mention if LDL target
values were present in that patient or if glycohemoglobin values were
controlled.
A directly measured LDL would be more appropriate for diabetes.
Apart from that diabetics have known complications even when everything is
done.
Hope you get some input from the other doctors out there.
Good luck
Robert - 04 Jun 2005 09:12 GMT
I forgot to mention the previous LDH questions.

I dusted off my old book and it only took a minute.

The pyruvate plus NADH plus H to pyruvate is optimal at pH 7.5-8.5
(isoenzymes 1,3 and 5 all similar pH).
The reverse reaction is greater at pH 9.5
(isoforms optima LD1,2 and 3 are about 0.15 pH apart)
The LDH has no function in the serum. The majority is from RBC's and
platelets and LDH appears to be inactivated in the circulation and the
inactive enzyme appear in the small intestine, excreted through biliary
tract.
There are 5 isoforms and in tissues rich in LD1 such as heart and RBC's ,
lactate could not form in the presence of excess pyruvate, whereas in
skeletal muscle which is rich in LD5, lactate could form. Based on that LD1
was termed the aerobic isoenzyme and LD5 the anaerobic isoform. It turned
out not to be the case under normal physiology. Pyruvate concentrations do
not control whether anaerobic or aerobic pathways are followed, rather the
redox state of the tissues. Lactate accumulates in the tissue during
anaerobic metabolism regardless of which LD isoenzyme is predominant.
As far as tissue concentrations go the brain has the highest, heart,RBC's,
kidney, lung then skeletal muscle.
The heart has about 25000 units/g with LD1,LD2,LD3 and very little LD4 and
LD5
skeletal muscle is 9000 units/g and pretty much even distribution of all
five isoforms.
kumar - 04 Jun 2005 10:39 GMT
Robert, many thanks again. God bless you.

Actually patient went for daily morning walk, experianced heavy sweat,
weakness but no chest pain or any other symptom. He went for check up
but doctor prefer to keep him in observation. ECG was normal with BP
normal. Doctors not considered for acidosis. Unfortunetely, Total LDH,
CK, troponin I &  (g) was done. Blood lactate test was not done. All
liver, kidney tests including AST was normal. Under lipids,
Triglyceride, LDL & HDL were mildly abnormal. He is ok now(after 10
days) but will go for re-check up, when he will be suggested to go for
angiography or not.

But when all symptoms do not indicated blockades, I just suspect,
whether this is due to some mild LA toxicity. LDH 582U (normal 350-618)
mat indicate something. Probably LDH heart isoenzmes might be higher at
that time--so some symptoms occured.
 
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