Chem Lect Unit 7 Kidney Function

CLINICAL CHEMISTRY
NON - PROTEIN NITROGEN
Introduction
NPN ( Non - Protein Nitrogen ) is a term that can be used for a bunch
of different substances that have the element nitrogen in them, but are
not proteins.
This is a little unusual, because most of the bodys nitrogen is
associated with proteins.
There are many different unrelated NPNs, but we are only interested in
4 of them:
Creatinine , Blood Urea Nitrogen ( BUN ) , Uric Acid and Ammonia
In general, plasma NPNs are increased in renal failure and are
commonly ordered as blood tests to check renal function
BUN ( Blood Urea Nitrogen )

Blood Urea Nitrogen = BUN = Urea
50% of the NPNs
Product of protein catabolism which produces ammonia
Ammonia is very toxic converted to urea by the liver
Liver converts ammonia and CO2
Urea
Filtered by the glomerulus but also reabsorbed by renal tubules ( 40 % )
Some is lost through the skin and the GI tract ( < 10 % )
Plasma BUN is affected by
Renal function
Dietary protein
Protein catabolism
3
BUN disease correlations

Azotemia = Elevated plasma BUN
Prerenal BUN ( Not related to renal function )
Low Blood Pressure ( CHF, Shock, hemorrhage, dehydration )
Decreased blood flow to kidney = No filtration
Increased dietary protein or protein catabolism
Prerenal BUN ( Not related to renal function )

Decreased dietary protein
Increased protein synthesis ( Pregnant women , children )
Renal causes of BUN

Renal disease with decreased glomerular filtration
Glomerular nephritis
Renal failure form Diabetes Mellitus
Post renal causes of BUN ( not related to renal function )

Obstruction of urine flow
Kidney stones
Bladder or prostate tumors
UTIs
5
BUN / Creatinine Ratio

Normal BUN / Creatinine ratio is 10 20 to 1
Creatinine is another NPN
Pre-renal increased BUN / Creat ratio
BUN is more susceptible to non-renal factors
Post-renal increased ratio BUN / Creat ratio

Both BUN and Creat are elevated
Renal decreased BUN / Creat ratio

Low dietary protein or severe liver disease
Increased BUN
Normal Creat
Increased BUN
Increased Creat
Decreased BUN
Normal Creat
BUN analytical methods

BUN is an old term, but still in common use
Specimen : Plasma or serum
To convert BUN to Urea : BUN x 2.14 = Urea ( mg / dl )
Urease
2 NH4+ + HCO3-
UREA
NH4
+ 2-OXOGLUTARATE
GLDH
NADH
GLUTAMATE
NAD
Measure the rate of decreased absorbance at 340 nm

NADH absorbs NAD does not absorb
Reference range :
10 20 mg / dl
CREATININE
Liver
Muscles
Muscles
Amino Acids
Creatine
Phosphocreatine
Creatine
Phosphocreatine
Creatinine
Creatinine formed at a constant rate by the muscles as a function of muscle mass

Creatinine is removed from the plasma by glomerular filtration
Creatinine is not secreted or absorbed by the renal tubules
Therefore : Plasma creatinine is a function of glomerular filtration
Unaffected by other factors
Its a very good test to evaluate renal function
8
Creatinine disease correlations

Increased plasma creatinine associated with decreased
glomerular filtration ( renal function )
Glomerular filtration may be 50 % of normal before plasma
creatinine is elevated
Plasma creatinine is unaffected by diet
Plasma creatinine is the most common test used to evaluate
renal function
Plasma creatinine concentrations are very stable from day to
day - If there is a delta check , its very suspicious and must be
investigated
9
Creatinine analytical techniques

Jaffee Method ( the Classic technique )
Creatinine + Picrate Acid
Colored chromogen
Specimen : Plasma or serum

Elevated bilirubin and hemolysis causes falsely decreased results
Reference range : 0.5 - 1.5 mg / dl
10
Uric acid
Uric acid is a chemical created when the body breaks
down substances called purines.
Purines are found in some foods and drinks, such as
liver, anchovies, mackerel, dried beans and peas, beer,
and wine.
Purines are also a part of normal body substances,
such as DNA.
In humans, approximately 75% of uric acid excreted is

lost in the urine; most of the reminder is secreted into the
GIT
If your body produces too much uric acid or doesn't
remove enough if it, you can get sick.
High levels of uric acid in the body is called
hyperuricemia
Normal values fall between 3.0 and 7.0 mg/dL.
Note: Normal values may vary slightly from laboratory to
laboratory.
When is it ordered?
when a doctor suspects high levels of uric acid :
Gout
monitoring test when a patient has undergone chemotherapy or
radiation
if a patient appears to have failing kidneys
Greater-than-normal levels of uric acid (hyperuricemia) may be due

to:
Alcoholism
Diabetes
Gout
Hypoparathyroidism
Lead poisoning
Leukemia
Nephrolithiasis
Polycythemia vera
Renal failure
Toxemia of pregnancy
Purine-rich diet
Excessive exercise
Chemotherapy-related side effects
Lower-than-normal levels of uric acid may be due to:
Fanconi syndrome
Wilson's disease
Syndrome of inappropriate antidiuretic hormone (SIADH)
secretion
Multiple Sclerosis
Low purine die
Gout
Gout is a kind of arthritis that occurs when uric acid builds up in
the joints.
In Gout increased serum levels of uric acid lead to formation of
monosodium urate crystals around the joints.
Acute gout is a painful condition that typically affects one joint.
Chronic gout is repeated episodes of pain and inflammation, which
may involve more than one joint.
The exact cause is unknown. Gout may run in families. It is more
common in males, postmenopausal women, and people who drink
alcohol
Symptoms of acute gouty attacks:

Symptoms develop suddenly and usually involve only
one or a few joints. The big toe, knee, or ankle joints
are most often affected.
The pain frequently starts during the night and is often
described as throbbing, crushing, or excruciating.
The joint appears warm and red. It is usually very
tender.
There may be a fever.
The attack may go away in several days, but may
return from time to time. Additional attacks usually
last longer.
After a first gouty attack, people will have no symptoms. Some

people will go months or even years between gouty attacks.
Some people may develop chronic gouty arthritis, but others may
have no further attacks. Those with chronic arthritis develop joint
deformities and loss of motion in the joints. They will have joint
pain and other symptoms most of the time.
Tophi are lumps below the skin around joints or in other places.
They may drain chalky material. Tophi usually develop only after a
patient has had the disease for many years.
After one gouty attack, more than half of people will have another
attack.
A tophus on the elbow of a middle aged man with chronic

gout.
Tests that may be done include:

Synovial fluid analysis
Gold standard to confirm gout,
Urate crystals identified by:
- Needle and rod shapes
Uric acid - blood
Joint x-rays )may be normal)
X-ray of gouty uric acid deposit in the big toe (left)
Possible Complications
Chronic gouty arthritis
Kidney stones
Deposits in the kidneys, leading to chronic kidney
failure
Treatment
Treatments for a sudden attack or flare-up of gout:
Your doctor will recommend that you take
nonsteroidal anti-inflammatory drugs (NSAIDs) such
as ibuprofen, naproxen, or indomethacin as soon as
your symptoms begin
Your health care provider may occasionally prescribe
strong painkillers such as codeine
Daily use of allopurinol decrease uric acid levels in
your blood
Some diet and lifestyle changes may help prevent

gouty attacks:
Avoid alcohol, sardines, oils, organ meat (liver,

kidney, and sweetbreads(
Limit how much meat you eat at each meal.
Avoid fatty foods such as salad dressings, ice cream,
and fried foods
Eat enough carbohydrates
If you are losing weight, lose it slowly. Quick weight
loss may cause uric acid kidney stones to form.
Specimen
Serum or plasma may be used; slight but
insignificant positive bias (0.2 mg/dL) has been
noted in plasma specimens as compared with
serum.
Stability in serum / plasma:
6 months at -20C
7 days at 4-8C
3 days at 20-25C
Enzymatic Colorimetric
1-Uric acid + H2O + O2
Uricase
Allantion + CO2 + H2O2
2-TBHBA + 4- Aminoantipyrine + 2H2O2

Quinoneimine + 3 H2O
POD
-Uric acid is oxidized to allantoin by uricase.

-The generated hydrogen peroxide reacts with 4aminophenazone/ESPT to quinoneimine.
Note:
Uric acid may also form kidney stones
Although uric acid can act as an antioxidant, excess
serum accumulation is often associated with
cardiovascular disease.
AMMONIA
Produced from the deamaination of amino acids in the muscle and
from bacteria in the GI tract
Ammonia is very toxic - The liver converts ammonia into urea
Urea is less toxic and can be removed from the plasma by the
kidneys
In severe hepatic disease, the liver fails to convert ammonia into
urea, resulting in increased plasma ammonia levels
Increased plasma ammonia concentrations in :
Liver failure
Reyes Disease
30
Ammonia analytical techniques

NH4+ + 2-OXOGLUTARATE + NADPH
L-GLUTAMATE +
NADP+
There is a decreasing absorbance @ 340 nm, proportional to the

ammonia concentration.
Specimen : EDTA or Heparinized Whole Blood on ice
Must be tested ASAP or plasma frozen
Delayed testing caused false increased values
Reference range : 20 60 g / dl
31
Creatinine Clearance
Calculated measurement of the rate at which creatinine is removed from
the plasma by the kidneys
Measurement of glomerular filtration ( renal function )
A good test of glomerular filtration because
Creatinine is an endogenous substance ( not affected by diet )

Creatinine is filtered by the glomerulus, but not secreted or
re-absorbed by the renal tubules
32
Creatinine Clearance specimens

24 hour urine specimen
Plasma / serum creatinine collected during the urine collection
24 Hour Creatinine Clearance Formula
CREATININE CLEARANCE =
UV 1.73
P
A
U=
V=
P =
Creatinine concentration of the 24 hour urine ( mg / dl )

24 hour urine volume ( mls ) per minute - V / 1440 = mls / minute
Plasma creatinine concentration ( mg / dl )
A =
Correction factor accounts for differences in body surface area

obtained from a height weight chart
33
Example of a 24 Hour Creatinine Clearance calculation

24 hour urine volume
= 1000 mls
24 hour urine creatinine = 20.0 mg / dl
Plasma creatinine
= 5.0 mg / dl
Patients height / weight = 600 / 190 lbs
Creat Cl
( see pg. 680 )
1000
20.0
UV 1.73
1440
P
A
5.0

Creat Cl =
2 ml / min
1.73

2.05
. Very poor clearance !!!

34
Procedure for 24 Hour Urine Collection

Have the patient empty his / her bladder ( discard this urine ).
Note the time . For the next 24 hours, have the patient collect and save all
urine in an appropriate container.
At the end of the 24 hour period have the patient void one last time into
the urine container. This completes the collection.
If possible, keep the urine specimen refrigerated.
35
Reference range
97 - 137 ml / min
88 - 128 ml / min
( male)
(female)
Lets remember 90 - 130 ml / min
36
NPN TOP 10
Increased Creatinine associated with renal failure

Increased BUN associated with renal failure and protein catabolism
Increased Uric Acid associated with Gout
Increased Ammonia is associated with liver disease
Creatinine derived from cellular creatine very constant from day to day
Delta checks on plasma Creatinine must be investigated !!!
BUN ( Urea ) is derived from protein catabolism

Protein
Ammonia
Urea
Uric Acid is derived from purine( a component of DNA ) catabolism
Decreased Creatinine Clearance associated with decreased Glomerular

Filtration
UV 1.73

P
A
Dont forget to divide V by 1440 !
37
Reference Ranges
BUN
10 - 20
Creatinine
0.5 - 1.5 mg /dl
Uric Acid
90 - 130 ml / min
Ammonia
ug / dl
BUN / Creat Ratio 10 - 20 to 1
mg / dl
3.0 - 7.0 mg / dl
20 - 60
38

Chem Lect Unit 7 Kidney Function

Uploaded by

Copyright:

Available Formats

Chem Lect Unit 7 Kidney Function

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Chem Lect Unit 7 Kidney Function

Uploaded by

Copyright:

Available Formats

CLINICAL CHEMISTRY

NON - PROTEIN NITROGEN

BUN ( Blood Urea Nitrogen )

BUN disease correlations

Prerenal BUN ( Not related to renal function )

Renal causes of BUN

Post renal causes of BUN ( not related to renal function )

BUN / Creatinine Ratio

Post-renal increased ratio BUN / Creat ratio

Renal decreased BUN / Creat ratio

BUN analytical methods

Measure the rate of decreased absorbance at 340 nm

Creatinine formed at a constant rate by the muscles as a function of muscle mass

Creatinine disease correlations

Creatinine analytical techniques

Specimen : Plasma or serum

In humans, approximately 75% of uric acid excreted is

Greater-than-normal levels of uric acid (hyperuricemia) may be due

Lower-than-normal levels of uric acid may be due to:

Symptoms of acute gouty attacks:

After a first gouty attack, people will have no symptoms. Some

A tophus on the elbow of a middle aged man with chronic

Tests that may be done include:

X-ray of gouty uric acid deposit in the big toe (left)

Some diet and lifestyle changes may help prevent

Avoid alcohol, sardines, oils, organ meat (liver,

Allantion + CO2 + H2O2

2-TBHBA + 4- Aminoantipyrine + 2H2O2

-Uric acid is oxidized to allantoin by uricase.

Ammonia analytical techniques

There is a decreasing absorbance @ 340 nm, proportional to the

Creatinine is an endogenous substance ( not affected by diet )

Creatinine Clearance specimens

Creatinine concentration of the 24 hour urine ( mg / dl )

Correction factor accounts for differences in body surface area

Example of a 24 Hour Creatinine Clearance calculation

( see pg. 680 )

. Very poor clearance !!!

Procedure for 24 Hour Urine Collection

Lets remember 90 - 130 ml / min

Increased Creatinine associated with renal failure

BUN ( Urea ) is derived from protein catabolism

Decreased Creatinine Clearance associated with decreased Glomerular

Dont forget to divide V by 1440 !

0.5 - 1.5 mg /dl

BUN / Creat Ratio 10 - 20 to 1

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.