Gout pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview


Pathophysiology

The pathophysiology of Gout mainly relates to hyperuricemia. Greater is the degree of hyperuricemia greater is the likelihood of developing Gout. There are numerous reasons that can lead to the development of increase in level of uric acids:

  • Enhanced or increased purine uptake.
  • Decreased excretion of uric acid
  • Increased production of uric acid

Although these are the most common responsible factors for the development of gout but still for lot of cases the rise in uric acid levels is still unknown.

Pathophysiology Of Gout
Increased Uptake of Purine Increased production of uric acid Decreased production of uric acid
- Increased uptake of purine rich foods

Like asparagus, herring, meat broths,

mussels, sweetbreads, liver, kidney.

- Beer drinking - Beer is rich in guanosine

which is a purine nucleotide also leads

to the increased level of purines.

- Even the diet strictly controlled for the

purine lowers serum urate by maximally

up to 1 mg/dl.

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Decreased renal excretion is by far the most common cause of hyperuricemia. It may be hereditary and also occurs in patients receiving diuretics and in those with diseases that decrease GFR. Ethanol increases purine catabolism in the liver and increases the formation of lactic acid, which blocks urate secretion by the renal tubules, and ethanol may also stimulate liver urate synthesis. Lead poisoning and cyclosporine, usually in the higher doses given to transplant patients, damage renal tubules, leading to urate retention.

Increased production of urate may be caused by increased nucleoprotein turnover in hematologic conditions (eg, lymphoma, leukemia, hemolytic anemia) and in conditions with increased rates of cellular proliferation and cell death (eg, psoriasis, cytotoxic cancer therapy, radiation therapy). Increased urate production may also occur as a primary hereditary abnormality and in obesity, because urate production correlates with body surface area. In most cases, the cause of urate overproduction is unknown, but a few cases are attributable to enzyme abnormalities; deficiency of hypoxanthine-guanine phosphoribosyltransferase (complete deficiency is Lesch-Nyhan syndrome) is a possible cause, as is overactivity of phosphoribosylpyrophosphate synthetase.

Increased intake of purine-rich foods (eg, liver, kidney, anchovies, asparagus, consommé, herring, meat gravies and broths, mushrooms, mussels, sardines, sweetbreads) can contribute to hyperuricemia. Beer is particularly rich in guanosine, a purine nucleoside. However, a strict low-purine diet lowers serum urate by only about 1 mg/dL.

Urate precipitates as needle-shaped monosodium urate (MSU) crystals, which are deposited extracellularly in avascular tissues (eg, cartilage) or in relatively avascular tissues (eg, tendons, tendon sheaths, ligaments, walls of bursae) and skin around cooler distal joints and tissues (eg, ears). In severe, long-standing hyperuricemia, MSU crystals may be deposited in larger central joints and in the parenchyma of organs such as the kidney. At the acid pH of urine, urate precipitates readily as small platelike or diamond-shaped uric acid crystals that may aggregate to form gravel or stones, which may obstruct urine outflow. Tophi are MSU crystal aggregates that most often develop in joint and cutaneous tissue. They are usually encased in a fibrous matrix, which prevents them from causing acute inflammation.

Acute gouty arthritis may be triggered by trauma, medical stress (eg, pneumonia or other infection), surgery, use of thiazide diuretics or drugs with hypouricemic effects (eg, allopurinol, febuxostat, probenecid, nitroglycerin), or indulgence in purine-rich food or alcohol. Attacks are often precipitated by a sudden increase or, more commonly, a sudden decrease in serum urate levels. Why acute attacks follow some of these precipitating conditions is unknown. Tophi in and around joints can limit motion and cause deformities, called chronic tophaceous gouty arthritis. Chronic gout increases the risk of developing secondary osteoarthritis.



Gross Pathology

Kidney: Uric Acid Deposition: Gross, an excellent example of gouty nephropathy with deposits and excavation in pyramids
Kidney: Papillary Necrosis: Gross, yellow foci in pyramids, a gout kidney
Bone, synovium: Gout: Gross natural color opened joint with extensive white deposits of uric acid
Bone, synovium: Gout: Gross natural color close-up of extensive uric acid deposits
Kidney: Gout: Gross natural color close-up view of uric acid deposit in medullary pyramid
Kidney: Uric Acid Deposition: Gross natural color close-up and excellent view of opaque material in medullary pyramid of adult kidney
Bone, synovium: Gout: Gross natural color section through sternum and clavicle showing very well uric acid deposits in the periarticular tissue
Urinary Tract: Staghorn calculi in renal pelvis, Gout
Gout; Bursa of Knee
Kidney: Uric Acid Deposition: Gross, infant kidney with excellent uric acid streaks
Kidney: Uric Acid Deposition: Gross good example uric acid streaks in medulla (very ischemic kidney)
Kidney: Uric Acid Nephropathy: Gross, natural color, an excellent view of hydronephrosis with inflamed pelvis and multiple calculi with deposits in medullary pyramids
Kidney: Uric Acid Infarcts: Gross natural color opened kidney showing marked ischemia with dark red medullary pyramids which contrast sharply with the uric acid deposits
Kidney: Uric Acid Infarcts: Gross natural color typical lesion well shown
Kidney: Uric Acid In Medulla: Gross natural color cut surface of kidney uric acid easily seen
Kidney: Uric Acid Infarcts: Gross natural color close-up outstanding photo of the uric acid streaks in medullary pyramids
Knee Joint: Gout. Heavy Deposition of Urate Crystals in Articular Cartilage

Microscopic Pathology

Gout (Needles, no birefringence, monosodium urate)
Skin: Tophus: Micro med mag H&E uric acid deposits with giant cells. Easily recognizable as gout or uric acid tophus
Skin: Tophus: Micro med mag H&E easily recognized uric acid deposit lesion from elbow
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout
Bones-Joints: Gout, alcohol fixed tissues, monosodium urate crystals
Bones-Joints: Gout, alcohol fixed tissues, monosodium urate crystals
Bones-Joints: Gout, alcohol fixed tissues, monosodium urate crystals
Bones-Joints: Gout
Bones-Joints: Gout
Joint: Gout
Joint: Uric Acid Crystals in Acute Gout

Sources

Copyleft images obtained courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA) Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

References

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