Gout

Represents a heterogeneous group of diseases in which the common denominator is an increased serum uric acid level and the deposition of sodium urate crystals in joints, soft tissue around joints and kidneys. 

 Pathogenesis of hyperuricemia:

•  Uric acid is the end product of the catabolism of purines, derived either from the diet or synthesized de novo.

•  Uric acid is eliminated from the body mostly through urine

•  Normal values of uric acid in the blood is 7.0 mg/dl in men and 6.0 mg/dl in women

•  Hyperuricemia can result from over production of uric acid, decreased urinary excretion of uric acid or a combination of both.

Classification:

 1.  Primary (idiopathic) Gout

•  In this category the causes that result in hyperuricemia are unknown, Most cases (75-90%) of so- called idiopathic Gout result from an as yet unexplained impairment of uric acid excretion by the kidney.

•  In minority of the cases, though the causes are unknown there is an over production of uric acid.

2. Secondary 

•  In this category the causes that result in Hyperuricemia are known

a.  Conditions that result in over production of uric acid

•  Most common cause of overproduction of uric acid is increased turnover of nucleic acids, as seen in leukemia and Lymphomas and after chemotherapy for cancer.

•  Accelerated ATP degradation for various reasons results in over production of uric acid

> Some genetic factors are also incriminated for over production of uric acid

 b. Conditions that result in Decreased urinary excretion of uric acid

-  The most common cause of decreased urinary excretion of uric acid is chronic renal diseases that lead to renal failure. In renal failure the clearance of uric acid is decreased, and with a fall in the rate of Glomerular filtrates, hyperuricemia ensues.

> Other factors are also incriminated as a cause of decreased urinary excretion of uric acid.

Pathology (Morphology):

•  When a sodium urate crystal precipitates from super saturated body fluids, they absorb fibronectin, complement, and number of other proteins of their surfaces. In phagocytizing those protein coated crystals, Neutrophiles release inflammatory mediators resulting in local inflammatory reaction 

•  Uric acid crystals may be found intracellularly in leukocytes of the synovial fluid. Extra cellular soft tissue deposits of these crystals (tophi), are surrounded by foreign body giant cells and an associated inflammatory response of mononuclear cells. These granuloma like areas are found in the cartilages and in any soft tissue around the joints.

•  Macroscopically, it appears as chalky, white deposits on the surfaces of extra- articular structures and soft tissues around joints.

•  Uric acid crystals also deposit in the kidney. 

 Clinical features:

There are four steps in the clinical course of gout:

1.  Asymptomatic hyperuricemia  

Precedes clinically evident gout by many years 

2.  Acute gouty arthritis

Initially there is a monoarticular involvement and later in the course of the disease, poly articular involvement with fever is common. 

3. Intercritical period

-  This is Asymptomatic interval between attacks

4. Tophaceous Gout

-  Develops in the untreated patient in the form of tophi in the cartilage, synovial membrane, tendons and soft tissue.

-  Thophus is a chalky; yellow white deposit of monosodium urate crystals. Classic locations are on the ear, heads, olecranon bursa, and in the Achilles tendon.

Urate stones

-  Constitute10 percent of all kidney stones  

Diagnosis: The presence of long needle- shaped crystals that are –vely bisfrinegent under polarized light is diagnostic of gout.

Summary

-  Gout represents a heterogeneous group of diseases where there is an increased serum uric acid revel and the depositions of sodium urate crystals in joints and soft tissues around joints and kidneys.

-  Hyperuricemia can result from over production of uric acid, decreased urinary excretion of uric acid or a combination of both.

-  Gout is classified as primary, in cases where the caused that resulting hyperuricemia are unknown. Where the causes are identified, it is classified as secondary.

-  The deposition of sodium urate crystals in joints results in elaboration of inflammatory mediators form neutrophiles, which results in inflammation of the joint or the soft tissue involved.

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.

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