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Nucleoprotein Metabolism Disorders and Lithogenesis

Q: What is the microscopic structure of a gouty tophus?

The microscopic structure of a gouty tophus (tophi urici) is characterized by the development of productive granulomatous inflammation around salt deposits. Under hematoxylin and eosin staining, the following elements are determined: Necrosis zone — the central area containing sodium urate crystals.Inflammatory infiltrate — forms around the crystals and consists of lymphocytes, macrophages, neutrophils, fibroblasts, as well as epithelioid and multinucleated foreign body giant cells.Sclerosis zone — proliferation of connective tissue at the periphery of the lesion as an outcome of chronic inflammation.

Urolithiasis et Goutta

For medical students2 min readUpdated 2026-10-10

Nucleoprotein metabolism disorders are accompanied by the accumulation of uric acid and the formation of specific deposits, whereas stone formation in various organs is driven by systemic and local factors.

Gouty tophiUrate aggregates with a granulomatous inflammatory reaction

Uric acid infarctMetabolic deposition of urates in the kidneys of newborns

Stone structureCan have a radial, layered, or mixed structure

Stone complicationsDuct obstruction, pressure ulcers, necrosis, and chronic inflammation

Primary and Secondary Gout

Gout is a prominent manifestation of purine metabolism disorders. Primary gout has an inherited, familial nature and is often combined with obesity, diabetes, and cholelithiasis. Crystals of sodium urate are deposited in the auricular cartilages, joints, and tendons.

Tissue necrosis develops around the salt deposits, triggering perifocal inflammation with the formation of giant cells, followed by connective tissue proliferation. The culmination of this process is the formation of tophi (tophi urici) and joint deformation. In the kidneys, urates clog the tubules, causing secondary atrophic and inflammatory processes.

Secondary gout develops as a complication of other pathologies:

Hematopoietic tissue tumors due to massive cell breakdown;
Endocrine disorders;
Kidney diseases leading to nephrosclerosis and impaired uric acid excretion.

Uric Acid Infarct of Newborns

This condition is not a true necrosis, but rather a distinct metabolic phenomenon characteristic of full-term newborns who have lived for at least two days.

Causes: Intensive metabolism in the first days of life and the natural adaptation of the kidneys to extrauterine conditions.
Morphology: Amorphous masses of sodium and ammonium urate precipitate in the lumen of the tubules and collecting ducts.
Macroscopic appearance: On a cross-section of the kidney, yellow-red streaks are visible, converging at the medullary papillae.

Etiology and Pathogenesis of Stone Formation

Stone formation in the body is associated with general metabolic disorders (lipid, carbohydrate, mineral) and local factors such as secretory stasis, inflammatory processes, and secretory dysfunction.

The process of calculus formation consists of two mandatory stages:

Formation of the organic matrix (colloidal component consisting of mucus, leukocytes, desquamated cells, and protein substances).
Crystallization of salts (crystalloid component).

Inflammation and stones mutually reinforce each other, creating a vicious cycle. Calculi are most frequently localized in the biliary and urinary tracts, the excretory ducts of the pancreas and salivary glands (sialolithiasis), as well as in the bronchi.

The chemical composition of calculi is diverse:

Gallstones: cholesterol, pigment, calcareous, and mixed.
Urinary stones: urates, phosphates, oxalates (having a rough surface resembling a mulberry), cystine, and xanthine stones.

Significance and Complications of Stone Formation

The presence of stones in organs can remain asymptomatic for a long time, but over time they cause severe complications:

Obstruction: impaired secret outflow leads to jaundice when biliary tracts are blocked or to hydronephrosis when a ureter is obstructed.
Pressure ulcers and necrosis: constant pressure of the stone on the organ wall causes its necrosis and perforation.
Inflammation: calculi constantly maintain a chronic infectious and inflammatory process.

Mnemonic

Gout affects joints and ears (tophi), while stones grow where there is secretory stasis, inflammation, and a preformed protein matrix.

Frequently asked questions

What changes develop in the kidneys in gout?

In gout, gouty nephropathy develops due to the deposition of urates in the interstitium and tubular epithelium. The following forms and changes are distinguished:

Chronic interstitial process — a slowly developing abacterial pyelonephritis leading to nephrosclerosis.
Acute renal blockade — obstruction of the lumen of tubules and collecting ducts by uric acid with their severe damage and the development of acute renal failure.
Lithogenesis — deposition of urate crystals in the collecting ducts and renal pelves.

The outcome of the pathology is the formation of a gouty shrunken kidney and the development of chronic renal failure.

What is the mechanism of pigment gallstone formation?

The mechanism of pigment gallstone formation is based on the crystallization of calcium bilirubinate in the organic matrix when its concentration increases. Pathogenesis depends on the subtype of calculi:

Black stones — form predominantly against the background of hemolysis (e.g., in sickle cell disease) and liver cirrhosis from unconjugated bilirubin salts.
Brown stones — form against the background of chronic inflammation in the intra- and extrahepatic bile ducts, including mucins, cholesterol, and bacterial components in the core.

The general mechanism involves secretory dysfunction or bile stasis, which leads to the precipitation of substances into the colloidal matrix.

What are the consequences of ureteral obstruction by a stone?

Ureteral obstruction by a stone leads to impaired urine excretion. Confirmed consequences include:

Hydronephrosis and hydroureter — signs of stone obstruction; renal atrophy is possible in hydronephrosis.
Inflammation — stones maintain chronic inflammation; pyelonephritis and renal abscesses are possible in urolithiasis.
Pressure ulcers and necrosis — occur due to the pressure of the stone on the tissue, with possible organ wall necrosis and perforation.
Nephrosclerosis — listed among the complications of urolithiasis.
Renal colic — also listed among the complications of urolithiasis.

When the ureter is blocked by a stone, anuria may occur.

What is the microscopic structure of a gouty tophus?

The microscopic structure of a gouty tophus (tophi urici) is characterized by the development of productive granulomatous inflammation around salt deposits. Under hematoxylin and eosin staining, the following elements are determined:

Necrosis zone — the central area containing sodium urate crystals.
Inflammatory infiltrate — forms around the crystals and consists of lymphocytes, macrophages, neutrophils, fibroblasts, as well as epithelioid and multinucleated foreign body giant cells.
Sclerosis zone — proliferation of connective tissue at the periphery of the lesion as an outcome of chronic inflammation.

Is a uric acid infarct a true necrosis?

No, a uric acid infarct is not a true necrosis. It is a metabolic phenomenon occurring in newborns during the first days of life as a reflection of renal adaptation to extrauterine conditions.

What main components are necessary for stone formation?

Stone formation requires two components: the creation of an organic matrix (colloidal component consisting of mucus, proteins, and inflammatory cells) and the subsequent crystallization of salts (crystalloid component).

What is the tissue reaction around salt deposits in gout?

Tissue necrosis develops around the deposits, alongside perifocal inflammation with a granulomatous reaction and the accumulation of giant cells, as well as the proliferation of connective tissue.

Go deeper

Morphological features of various types of urinary stones (urates, oxalates, phosphates)
Microscopic structure of tophi and giant cell reaction
Connection between urolithiasis and gout and uric acid diathesis
Macroscopic forms of stones (faceted and staghorn calculi)
Role of inflammation in maintaining the vicious circle in lithogenesis