Gout
Gout (hyperuricemia): disorder characterized by high level of uric acid.
under excretion of uric acid
over production of uric acid
Main cause in most patients with gout:
Inherited excretory defect of the kidney
Excessive consumption of ethanol (because it decreases excretion of uric acid)
defect of one or more of enzymes of purine synthesis
Genetic mutation of PRPP synthetase (Phosphoribosyl pyrophosphate)
responsible for purine synthesis
purines are synthesized in excess and degraded to uric acid
Lesch-Nyhan syndrome
genetic defect in HGPRT (Hypoxanthine-guanine phosphoribosyltransferase)
leads to inability to reuse purines so they are degraded to uric acid
X-linked recessive disease
Lesch-Nyhan syndrome symptoms:
abnormally increased levels of uric acid
mental retardation and neurological symptoms
self-mutilating behaviors, such as: lip and finger biting and/or head banging
In Infants:
Urate crystal formation
presence of orange colored deposits (“orange sand”)
a cause outside the pathway of purine synthesis
Increase nuclei acids in diet by eating excess meat
Increased cellular breakdown as in malignancy and treatment with anticancer drugs that destroy cancer cells
Von-Gierke disease: a genetic disease, deficiency of glucose-6-phosphatase
Arises from low solubility of uric acid in body fluids, so insoluble sodium urate crystals precipitate into:
joints
kidneys
soft tissues
deposition of needle shaped urate crystals in joints causing severe inflammation (gouty arthritis)
big toe joint most commonly affected
joints of: feet, ankles, knees, wrists, fingers, and elbows also affected
may be accompanied by fever
joints are: swollen, red, hot, painful
Deposition of sodium urate crystals in the kidney causing uric acid stones
Nodular masses of sodium urate crystals (tophi) may be deposited under the skin
Rapid pain relief in acute attacks
Prevention of future gout attacks and the complications, by decreasing formation of uric acid
analgesics and anti-inflammatory
colchicine decreases movement of granulocytes into affected area
colchicine and non-steroidal anti-inflammatory drugs can be used prophylactically to prevent acute attacks in patients with gout
analog of hypoxanthine
competitive inhibitor to xanthine oxidase
accumulation of hypoxanthine (more soluble than uric acid)
used for long term therapy of gout
Allopurinol is a suicide enzyme inactivator
suicide inhibition: a type of inhibition in which a substrate analog is converted to an inhibitor not released from the enzyme active site
effective in regulation of hyperuricemia and prevention of tophii
increase solubility of uric acid in urine
avoid purine rich foods
drink a lot of water
Gout (hyperuricemia): disorder characterized by high level of uric acid.
under excretion of uric acid
over production of uric acid
Main cause in most patients with gout:
Inherited excretory defect of the kidney
Excessive consumption of ethanol (because it decreases excretion of uric acid)
defect of one or more of enzymes of purine synthesis
Genetic mutation of PRPP synthetase (Phosphoribosyl pyrophosphate)
responsible for purine synthesis
purines are synthesized in excess and degraded to uric acid
Lesch-Nyhan syndrome
genetic defect in HGPRT (Hypoxanthine-guanine phosphoribosyltransferase)
leads to inability to reuse purines so they are degraded to uric acid
X-linked recessive disease
Lesch-Nyhan syndrome symptoms:
abnormally increased levels of uric acid
mental retardation and neurological symptoms
self-mutilating behaviors, such as: lip and finger biting and/or head banging
In Infants:
Urate crystal formation
presence of orange colored deposits (“orange sand”)
a cause outside the pathway of purine synthesis
Increase nuclei acids in diet by eating excess meat
Increased cellular breakdown as in malignancy and treatment with anticancer drugs that destroy cancer cells
Von-Gierke disease: a genetic disease, deficiency of glucose-6-phosphatase
Arises from low solubility of uric acid in body fluids, so insoluble sodium urate crystals precipitate into:
joints
kidneys
soft tissues
deposition of needle shaped urate crystals in joints causing severe inflammation (gouty arthritis)
big toe joint most commonly affected
joints of: feet, ankles, knees, wrists, fingers, and elbows also affected
may be accompanied by fever
joints are: swollen, red, hot, painful
Deposition of sodium urate crystals in the kidney causing uric acid stones
Nodular masses of sodium urate crystals (tophi) may be deposited under the skin
Rapid pain relief in acute attacks
Prevention of future gout attacks and the complications, by decreasing formation of uric acid
analgesics and anti-inflammatory
colchicine decreases movement of granulocytes into affected area
colchicine and non-steroidal anti-inflammatory drugs can be used prophylactically to prevent acute attacks in patients with gout
analog of hypoxanthine
competitive inhibitor to xanthine oxidase
accumulation of hypoxanthine (more soluble than uric acid)
used for long term therapy of gout
Allopurinol is a suicide enzyme inactivator
suicide inhibition: a type of inhibition in which a substrate analog is converted to an inhibitor not released from the enzyme active site
effective in regulation of hyperuricemia and prevention of tophii
increase solubility of uric acid in urine
avoid purine rich foods
drink a lot of water