Uric acid is produced through the breakdown of purines in the liver and transported to the kidneys. The kidneys filter uric acid from the blood and most is reabsorbed, with about 300mg excreted daily in urine. High levels of uric acid can cause deposition of urate crystals in the joints, leading to painful gout. Gout progresses through asymptomatic, acute arthritic attacks, and chronic stages with tophi formation. Various disorders and medications can cause hyperuricemia by increasing production or decreasing excretion of uric acid.
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Uric Acid: Production, Excretion, Hyperuricemia, and Gout
1.
2. URIC ACID
Uric acid is a waste product created during the normal
breakdown of purines, naturally occurring substances found in
foods such as liver, mushrooms, and dried beans etc.
Uric acid is normally cleaned out of the blood by the kidneys,
and passes out of the body along with urine
3. Chemically
• Uric acid is a nitrogenous compound
• (2,6,8 Tri hydroxypurine).
• Principal nitrogenous component of excrement of
reptiles and birds.
• Small amount in mammalian Urine and its salts occours
in the joints in gout.
4. Uric acid
Uric acid is a heterocyclic compound of
Carbon
Hydrogen
Nitrogen and
Oxygen
Formula : C5H4N4O3.
5. Bichemistry
• In humans, uric acid is the major product of the catabolism of
the purine nucleosides adenosine and guanosine
• Purines from catabolism of dietary nucleic acid are converted
to uric acid directly.
• The bulk of purines excreted as uric acid
arise from degradation of endogenous nucleic acids.
• The daily synthesis rate of uric acid is approximately 400 mg.
• Dietary sources contribute another 300mg.
• In men consuming a purine-free diet, the total body pool of
exchangeable urate is estimated at 1200 mg.
6. Gouty arthritis
• By contrast, patients with gouty arthritis and tissue
deposition of urate may have urate pools as large as
18,000 to 30,000 mg.
•
Overproduction of uric acid may result from increased
synthesis of purine precursors.
7. URIC ACID
•produced through catabolism of purines nuclic acids(adenosine
and guanine) in the liver,
•transported to kidney, filtered through glomerulus, most of which
Is reabsorbed in the proximal tubules.
Reabsorptin :
98-100% in proximal tubules.
Excretion :
through urinary system = 70%
Through GIT = 30%
Daily synthesis rate of uric Acid is 400 mg
Dietary source 300mg
8. Cont….
Uric acid is insoluble in plasma and at high concentrations can be
deposited in the joints and tissue, causing painful inflammation.
9. Renal Handling
Renal handling of uric acid is complex and involves four
sequential steps
1.glomerular filtration of virtually all the uric acid in capillary plasma
entering the glomerulus;
2.reabsorption in the proximal convoluted tubule of about 98% to 100%
of filtered uric acid;
3.subsequent secretion of uric acid into the lumen in the distal portion of
the proximal tubule;
4.further reabsorption in the distal tubule. The net
urinary excretion of uric acid is 6% to 12% of the amount
filtered.
.
10. Cont…..
• Approximately 8 to 12 % of the filtered urate is excreted
in the urine as uric acid.
• Uric acid in urine exists as mono and disodium,
potassium, ammonium and calcium urates.
• An average adult on a low protein diet excretes
approximately 275 to 600 mg of uric acid in a 24 hours
period.
11. Clinical applications
Uric acid is measured to assess :
•Diagnosis and monitor treatment of gout.
•Diagnosis of renal calculi
•To detect kidney function.
• Inherited disorders of purine metabolism
13. Two methods for uric acid measurement are commonly used in
the clinical laboratory:
•Uricase
•Phosphotungstic acid.
14. Uricase Method:
•it is highly specific
The hydrogen peroxide produced is reacted with chromogen in
the presence of peroxidase enzyme, produces red Colour, the
intensity of which is proportional to the amount of uric acid present
in the sample.
15. Phosphotungstate Method:
•it is non specific
The phosphotungstic acid reagent reacts with uric acid in alkaline
solution. This oxidise uric acid to allantoin and is itself reduced to
tungsten which is blue in colour. The intensity of the blue colour is
proportional to the amount of uric acid
17. Factors affecting uric acid level
•Sex: higher in males due to increase body mass
•Body mass: level is increased in obesity.
•Diet: increased in meet intake, decreased fluid intake leads to
increased retention of uric acid by the kidney.
•Exercise
•Pregnancy
18. HYPERURICEMIA
•A term used to describe individuals who have increased uric acid in the
blood. Such individuals may be asymptomatic, but are at increased risk
for associated renal problems.
•Hyperuricemia
is defined as a serum urate concentration greater than 7mg/dl (416
umol/L) and may result from a number of disorders and conditions
associated with increased urate production and/ or decreased renal
excretion.
•Hyperuricemia
•Hyperuricemia is most commonly defined by plasma uric acid
concentrations greater than 7.0 mg/dL (0.42 mmollL) in men
or greater than 6.0 mgldL (0.36 mmol/L) in women. The major
causes of hyperuricemia are summarized
19. HYPERURICEMIA
•Gout
•Sepsis
•Inherited disorders
•Anaemia ( hemolytic or megaloblastic anaemia)
•Leukaemias
•Lymphomas
•Polycythemia,
•chronic renal disorders
•Serum uric acid can be elevated due to reduced excretion by the kidneys.
•Ingestion of certain drugs (ethanol, cytotoxic drugs)
•Excessive consumption of purine rich foods (meats, viscera, leguminous vegetables)
•Obesity
23. • Gout comprises a heterogeneous group of disorders
characterized by:
1. Hyperuricemia
2. Attack of acute inflammatory arthritis
3. Deposition of monosodium urate crystals through out
the body (tophi).
4. Nephrolithiasis
GOUT
24. The four phases of gout
progression include
• :
a) Asymptomatic hyperuricemia
b) Acute gouty arthritis
c) Intercritical gout (intervals b/w acute attacks)
d) Chronic tophaceous gout
25. Cont….
• Gout is much more common in men than women.
• Gout in women occurs exclusively after menopause.
• Acute gout most commonly affects the first metatarsal joint of foot.
• Recent studies have shown that as many as 98% individuals with gout
have a defect in the renal handling of uric acid.
• The acute inflammation in gout is a result of the interaction between
monosodium urate deposits in the tissues and polymorph nuclear
Leukocytes with a subsequent release of lysosomal enzymes,
leukotrienes,
• prostaglandins and protease.
26. Abnormal serum uric acid level in endocrine disorders
• Among the factors, which may influence on the uric acid
metabolism,
• the excess or deficiency of some hormones apparently
induces the
• abnormal serum uric acid level. We described
hyperuricemia and
• hypouricemia associated with endocrine disorders.
Hyperuricemia due to
• ).
27. Cont…….
• The increased production of uric acid is observed in myopathy
associated with hypothyroidism, hyperthyroidism or
hypoparathyroidism.
• Hyperuricemia due to the decreased renal uric acid clearance
is associated
• with hypopituitarism, hypothyroidism, hyperparathyroidism,
central diabetes insipidus, nephrogenic diabetes insipidus,
Bartter syndrome, and diabetic ketoacidosis.
• Hypouricemia due to the increased renal uric acid clearance
is associated with hypoparathyroidism, primary aldosteronism
and inappropriate secretion of antidiuretic hormone (SIADH
28. Uric acid stone formation
Saturation levels of uric acid in blood may result in one form of
kidney stones when the urate crystallizes in the kidney. These uric
acid stones are radiolucent and so do not appear on an abdominal
plain X-ray, and thus their presence must be diagnosed by ultrasound
for this reason or stone protocol CT. Very large stones may be
detected on X-ray by their displacement of the surrounding kidney
tissues