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Lecture 3 - Uric Acid & Gout

Clinical Chemistry

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Abdoulhaleem Mo
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17 views31 pages

Lecture 3 - Uric Acid & Gout

Clinical Chemistry

Uploaded by

Abdoulhaleem Mo
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Uric Acid & Gout

Purine degradation & Gout


(Musculoskeletal Block)
•Purine degradation pathway
•Fate of uric acid in humans
•Gout and hyperuricemia:

•Biochemistry
•Types
•Treatment
Purine degradation pathway

 The major source of dietary nucleic acids


(purines and pyrimidines) is meat
 Purine and pyrimidine bases are absorbed by
the intestine
 The ingested bases are mostly degraded into
different products by degradation pathways
 These products are then excreted by the body
Dietary
Nucleotides
DNA / RNA
Pancreatic
nucleases Nucleotidases

Nucleosides

Nucleosidases

Uric acid Free purine bases + Ribose


Purine
Degradation
pathway
Purine degradation pathway

 Adenosine and guanosine (purines) are


finally degraded to uric acid by:
 Purine degradation pathway
CATABOLISM OF PURINES
AMP
Deaminase
AMP IMP XMP GMP
NTDase NTDase NTDase NTDase

ADA
Adenosine Inosine Xanthosine Guanosine
PNP PNP PNP
Xanthine
Oxidase GDA
Hypoxanthine Xanthine Guanine
Xanthine Oxidase

Uric acid
Fate of uric acid in humans
 In humans, primates, birds and reptiles the
final product of purine degradation is uric
acid
 Uric acid is excreted in the urine
 Some animals convert uric acid to other
products:
 Allantoin

 Allantoic acid
 Urea

 Ammonia
Fate of uric acid
Uric Acid Primates, Birds, Reptiles and insects
Urate Oxidase
Allantoin Other mammals
Allantoinase
Allantoic acid Teleost Fish
Allantoicase
Urea Cartilagenous fish and Amphibia
Urease
Ammonia Marine invertebrates
Fate of uric acid in humans
 Uric acid is less soluble in water
 Reptiles, insects and birds excrete uric acid as
a paste of crystals
 To save water
 Humans excrete uric acid in urine
Fate of uric acid in humans
 Humans do not have enzymes to further
degrade uric acid
 Excessive production of uric acid causes
deposition of uric acid crystals in the joints
leading to:
 Gout

 Hyperuricemia
Gout
Once fashionable to associate gout with intelligence
 people with gout:

 Isaac Newton
 Benjamin Frankin

 Martin Luther

 Charles Darwin

 Samuel Johnson
Disease of the riches
Gout
 Gout is a disease due to high levels of uric
acid in body fluids

 7.0 mg/dL and above

 Uric acid accumulates because of:


 Overproduction or
 Underexcretion
Gout
 prevails mainly in adult males

 rarely encountered in premenopausal women

 Sodium urate/uric acid may also precipitate in


the kidneys and ureters as stones, resulting in
renal damage and urinary tract obstruction
Gout
 Painful arthritic joint inflammation due to
deposits of insoluble sodium urate crystals
(especially big toe)

 Affects 3 per 1000 persons

 Sodium urate crystals accumulate in kidneys,


ureter, joints leading to chronic gouty arthritis
Voet Biochemistry 3e
© 2004 John Wiley & Sons, Inc.

Sodium urate crystals in urine


Gout
 Inaccurately associated with overeating and
drinking
 Alcohol used to be contaminated with lead
during manufacture and storage
 Lead decreases excretion of uric acid from
kidneys causing hyperuricemia and gout
 Excessive meat comsumption increases uric
acid production in some individuals
Gout

 Two main causes

 Overproduction of uric acid

 Underexcretion of uric acid


Hyperuricemia- soft tissues
 Nodular masses of
monosodium urate crystals
(tophi) may be deposited in
the soft tissues, resulting in
chronic tophaceous gout
 Hyperuricemia is typically
asymptomatic and does not
lead to gout, but gout is
preceded by hyperuricemia
Overproduction of uric acid
 Primaryhyperuricemia is, for the most part, idiopathic
(having no known cause)

 Secondary hyperuricemia is typically the


consequence of increased availability of purines, for
example, in patients with myeloproliferative disorders
or who are undergoing chemotherapy and so have a
high rate of cell turnover
Underexcretion of uric acid
 Underexcretion can be
 Primary- due to as-yet-unidentified inherent

excretory defects
 secondary to known disease processes that affect

how the kidney handles urate, for example lactic


acidosis, and to environmental factors such as the
use of drugs, for example, thiazide diuretics, or
exposure to lead
Diagnostic features
 usually affect joints in the
lower extremities (95%)
 onset is fast and sudden

 pain is usually severe; joint

may be swollen, red and hot


 attack may be accompanied

by fever, leukocytosis and an


elevated ESR
Diagnosis
 The definitive diagnosis of
gout requires aspiration
and examination of
synovial fluid from an
affected joint (or material
from a tophus) using
polarized light microscopy
to confirm the presence of
needle-shaped
monosodium urate crystals
Monosodium urate crystals
Nonpharmacological Approaches
 Avoid purine rich foods:
 red meat and organ meat (liver, kidneys)

 shellfish, anchovies, mackerel, herring

 meat extracts and gravies

 peas and beans, asparagus, lentils

 alcoholic beverages

 Weight loss
 Control alcohol
Treatment of gout- Acute attacks
 Acute attacks of gout are treated with anti-
inflammatory agents. Colchicine, steroidal drugs such
as prednisone, and nonsteroidal drugs such as
indomethacin are used
 Colchicine depolymerizes microtubules, thus

decreasing the movement of neutrophils into the


affected area.
Treatment - Long term
 Involves lowering the uric acid level below the saturation
point, thereby preventing the deposition of urate crystals
 Uricosuric agents- probenecid or sulfinpyrazone, that
increase renal excretion of uric acid
 Allopurinol, an inhibitor of uric acid synthesis

 Allopurinol is converted in the body to oxypurinol, which


inhibits xanthine oxidase, resulting in an accumulation
of hypoxanthine and xanthine—compounds more
soluble than uric acid and, therefore, less likely to
initiate an inflammatory response
References
 Lippincott 4th
Edition
 Voet & Voet

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