Gout pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

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
  • Etiology in lot of cases with rise in uric acid levels is still unknown.


Increased intake

The increased uptake is mainly related to

  • Increases intake of purine rich food substances by the patient such as
    • Asparagus, met broths, mushrooms, liver, kidney, sweetbreads, .
    • The increased intake of all of these substances can increase the risk of accumulation of more and more purines ultimately resulting in the excess of uric acid.
  • Beer is also particularly rich in guanosine which is a purine nucleotide.


Increased production

The increased production is mainly related to conditions associated with

  • Increase in turn over of of cells like in various hematological conditions such as Hemolytic anemia, leukemia and lymphoma.
  • Conditions associated with increase rate of cell proliferation and cell death.
    • Cytotoxic therapy
    • Radiation
    • Psoriasis
  • Obesity - As the urate production is directly proportional to the body surface area
  • Hereditary conditions
  • Enzyme abnormalities
    • Overactivity of Phosphoribosyl transferase
    • Deficiency of HGPRT
    • Absence of HGPRT ( Lesch-nyhan syndrome)

Decreased/Reduced renal excretion

This is the most common cause of hyperuricemia. Various factors responsible for its reduced elimination are:

  • Hereditary
  • Compromised renal function ( Reduced GFR)
  • On Diuretics
  • Alcohol intake
    • The lactic acid blocks the excretion of urate from the from the renal tubules. Alcohol induces the purine metabolism in the liver and increases the formation of lactic acid and
    • Alcohol also directly stimulates the synthesis of urate by the liver
  • Drugs like cyclosporine that are toxic to the renal tubules leads to the decreased elimination of uric acid and ultimately resulting in the urate retention.







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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