Transcript creatinine, urea andx

Creatinine
 Creatinine is the waste product formed in muscle
from a high energy storage compound ,creatine
phosphate (phosphocreatine).
 ATP is the immediate source of energy for muscular
contraction as it hydrolyzed to ADP.
 Creatine phosphate can be stored in muscle at 4
times the concentration ATP.
 Small amount of creatinine is ingested as constituent
of meat.
 Creatinine is the best indicator of renal function
than others. The amount of creatinine excreted daily
is a function of the muscle mass and is not affected
by diet, age and sex.
Schema for the formation of creatinine in muscle.
CK (creatine kinase)
Creatine phosphate and ADP are converted by enzymatic
action to creatine and ATP. A side reaction occurs and small
portion of the creatine phosphate loses its phosphate as
phosphate ion, with closure of the ring to form creatinine.
Normal range of creatinine in serum:
adult male: 0.7-1.4 mg/dl
female: 0.6-1.3 mg/dl
children: 0.4-1.2 mg/dl
Increase concentration
A) Prerenal factor:
- Congestive heart failure
- Shock
- Salt and water depletion associated with
vomiting, diarrhea, uncontrolled diabetes,
excessive use of diuretics and excessive sweating.
B) Renal factors:
- Involve damage to glomeruli, tubules, renal blood
vessels.
C) Postrenal factors:
- Prostatic hypertrophy
- Neoplasms compressing the ureters
- Calculi blocking the ureters
- Congenital abnormalities that compress or block
the ureters
Decrease concentration
Low serum creatinine concentration has no clinical
significance
Urine creatinine
The concentration of creatinine in urine is much higher than in
serum (about 1mg/ml).
Normal range of urine creatinine concentration (roughly): Men:
2.0 g/ 24 hours
women: 1.6 g/24 hours
Children: new born 7 mg/kg/24 hours
1.5-22 mo: 5 mg/kg/24 hours
2.5-3.5 years: 9 mg/kg/24 hours
4-10 years: 15 mg/kg/24 hours
Creatinine Clearance
 The most sensitive method of assessing renal function.
 Provide an estimate of the amount of the plasma that must
have flowed through the kidney glomeruli per minute with
the complete removal of creatinine to account for
creatinine per minute actually appearing in the urine.
 The creatinine clearance is calculated as
U/S X V where u creatinine concentration in urine
S creatinine concentration in serum
V volume of urine excreted per minute
120±25 ml/min for male
112±20 ml/min for female
Estimation of creatinine clearance
 A number of formulae exist for predicting creatinine clearance
(or GFR) from plasma [creatinine] and other readily available
information, such as age, sex and weight. The best known of these
is that of Cockcroft and Gault (1976):
 Creatinine clearance = (140 − age) × wt × (0.85 if patient is female)
0.814 × serum[creatinine]
 (creatinine clearance in ml/min, age in years, weight in kg,
[creatinine] in μmol/L).
Blood Urea Nitrogen (BUN)
 When protein are ingested, they are hydrolyzed to
amino acids (a.a).
 Amino acids are used for anabolic or catabolic.
 Excess proteins cannot be stored in the body.
 The amino α-group of all a.a that are broken down
in the mammalian body, end up in the urea
compound.
 Urea appears in renal glomerular filtrate in the same
concentration as in plasma, 40% urea is reabsorbed
in renal tubule.
 As with creatinine, the serum urea rises with
impairment renal function.
Serum concentration of urea is affected strongly
by the degree of protein catabolism.
In the case of diet, a change to high protein diet
can double the serum urea, and a low protein
intake can reduce it by half.
A) Illustration of the fate of ingested protein
B) The reaction that occurs when urea is split by urease
Urea formation pathway
Urea cycle
 Urea production occurs
almost exclusively in
liver.
 Urea is produced from
ammonia in five
enzymatic steps.
1) Carbamoyl phosphate
synthetase I.
2) Ornithine
transcarmoylase.
3) Argininosuccinate
synthetase.
4) Argininosuccinase.
5) arginase
Normal range of serum urea
concentration: 15-45mg/dl
Increase concentration
 high protein diet
 Administration of cortisollike steroids
 Stressful situation
 Prerenal, renal, and
postrenal factors
Decrease concentration
 late in pregnancy
 Starvation
 Low protein diet
Uric acid
 Uric acid is a purine compound that circulated in
plasma as sodium urate and is excreted by kidney.
 It is derived from the breakdown of nucleic acid.
 Uric acid are ingested or come from the destruction
of tissue cells and synthesized in the body from
simple compounds.
 Urate appears in the glomerular filtrate and partially
reabsorbed in tubules.
 Urate is of low solubility in plasma and uric less.
 Urate deposition in the kidney may lead to renal
failure
 There is a danger of precipitation of uric acid crystal
where there is local rise in H+ concentration.
Schematic representation of uric acid formation and excretion
Purines catabolism in
other organisms
 Uric acid is the excreted end
product of purine
catabolism in primates,
birds, and some other
animals.
 In most mammals and many
other vertebrates , uric acid
is further degraded to
allantoin by the action of
urate oxidase.
 In other organisms the
pathway is further extended
as shown
Illustration of uric acid pathway
Purines catabolism
 Purine nucleotides are degraded by
pathway in which they lose their
phosphate through the action of
5‘-nucleotidase.
 Adenylate yields adenosine, which is
deamination to inosine by the action
of adenosine deaminase.
 Inosine is hydrolyzed to
hypoxanthine and D-ribose.
 Hypoxanthine is oxidized
successively to xanthine and then
uric acid by xanthine oxidase .
 GMP catabolism also yields uric acid
as end product.
Gout disease

Gout is a form of acute arthritis that causes severe pain and swelling in
the joints. It most commonly affects the big toe, but may also affect the
heel, ankle, hand, wrist, or elbow. It affects the spine often enough to
be a factor in back pain. Gout usually comes on suddenly, goes away
after 5-10 days, and can keep recurring. Gout is different from other
forms of arthritis because it occurs when there are high levels of uric
acid circulating in the blood, which can cause urate crystals to settle in
the tissues of the joints
Normal range of uric acid:
male: 3.5-7.5 mg/dl female: 2.5-6.5 mg/dl children: 2.0-5.5 mg/dl
Increase concentration
Decrease concentration
 Gout disease
 Renal disease
 After increased breakdown of
nucleic acid and
nucleoprotein ( leukemia,
polycythemia, toxemia of
pregnancy, and after
irradiation of x-ray sensitive
carcinomas)
 After the administration of
ACTH or cortisol – like steroids
 Certain drugs that decrease
the reabsorption of urate by
renal tubules ( aspirin,
probenecid, penicillamine)
 by drugs (allopurinol) that
block a step in formation of
uric acid.
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. Primary hyperuricemia
Increased production of uric acid from purine
kidneys cannot get rid of the uric acid in blood, resulting in high levels
Secondary hyperuricemia
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Certain cancers, or chemotherapy agents may cause an increased turnover rate of cell death.
This is usually due to chemotherapy, but high uric acid levels can occur after chemotherapy is
administered.
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After chemotherapy, there is often a rapid amount of cellular destruction, and tumor lysis
syndrome may occur. Tumor lysis syndrome like in certain types of leukemia, lymphoma, or
multiple myeloma,
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Medications - can cause increased levels of uric acid in the blood
Endocrine or metabolic conditions -certain forms of diabetes, or acidosis can cause
hyperuricemia
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Elevated uric acid levels may produce kidney problems, or none at all. People may live many
years with elevated uric acid levels, and they do not develop gout or gouty arthritis (arthritis
means "joint inflammation").