PATHOPHYSIOLOGY

uric acid - end product of the degradation of purines(waste product)

The purines three sources: dietary purine, conversion of tissue nucleic acid to purine nucleotides, and de novo synthesis of purine bases.
An in the activity of phosphoribosyl pyrophosphate (PRPP) synthetase leads to an [ ] of PRPP (purine synthesis -uric acid (u.a) production). hypoxanthineguanine
phosphoribosyl transferase (HGPRT) is responsible for the conversion of guanine to guanylic acid and hypoxanthine to inosinic acid. A deficiency in the HGPRT enzyme
-metabolism of guanine and hypoxanthine to (u.a) and more PRPP to interact with glutamine in the first step of the purine pathway. Complete absence of HGPRT results
in the childhood Lesch-Nyhan syndrome, characterized by choreoathetosis, spasticity, mental retardation, and markedly excessive production of (u.a).
(u.a)- overproduced - breakdown of tissue nucleic acids, as with myeloproliferative and lymphoproliferative disorders. Cytotoxic drugs - overproduction of (u.a) due to
lysis and breakdown of cellular matter.
Drugs - renal clearance of (u.a) -diuretics, nicotinic acid, salicylates (less than 2 g/day), ethanol, pyrazinamide, levodopa, ethambutol, cyclosporine, and cytotoxic drugs.
The average human produces 600 to 800 mg of (u.a) daily and excretes less than 600 mg in urine. Individuals who excrete more than 600 mg after being on a purine-free
diet for 3 to 5 days are considered overproducers. Hyperuricemic individuals who excrete less than 600 mg of uric acid per 24 hours on a purine-free diet are defined as
underexcretors of (u.a). On a regular diet, excretion of more than 1,000 mg per 24 hours reflects overproduction; less than this is probably normal.
Deposition of urate crystals in synovial fluid results in an inflammatory process involving chemical mediators that cause vasodilation, vascular permeability,
complement activation, and chemotactic activity for polymorphonuclear leukocytes. Phagocytosis of urate crystals by leukocytes results in rapid lysis of cells and a
discharge of proteolytic enzymes into the cytoplasm. The ensuing inflammatory reaction is associated with intense joint pain, erythema, warmth, and swelling.
Uric acid nephrolithiasis occurs in 10% to 25% of patients with gout. Predisposing factors include excessive urinary excretion of uric acid, acidic urine, and highly
concentrated urine.
In acute (u.a) nephropathy, acute renal failure occurs as a result of blockage of urine flow secondary to massive precipitation of uric acid crystals in the collecting ducts
DIAGNOSIS
-identification of intracellular crystals of monosodium urate monohydrate in synovial fluid
leukocytes (joint aspiration)

-characterized by rapid onset of excruciating pain, swelling, and inflammation- first metatarsophalangeal joint (podagra),
and then ankles, heels, knees, wrists, fingers, and elbows.
begin at night, with the patient awakening from sleep with excruciating pain. The affected joints are erythematous, warm, and swollen. Fever and leukocytosis are co
attacks may last from 3 to 14 days before spontaneous recovery.
-attacks may be precipitated by stress, trauma, alcohol ingestion, infection, surgery, rapid lowering of serum uric acid by ingestion of uric acidlowering agents, and in

-presence of the characteristic signs and symptoms, as well as the response to treatment.

CLINICAL PRESENTATION

gout - attacks of acute arthritis = with monosodium urate crystals in leukocytes

found in synovial fluid, tissues (tophi), interstitial renal disease, and uric acid
nephrolithiasis.
Hyperuricemia increased serum uric acid [ ] >7.0 mg/dL

Gout and
Hyperuricemia

TREATMENT
The goals in the treatment of gout are to terminate the acute attack, prevent recurrent attacks of gouty arthritis, and prevent complications associated with chronic depositio