Urinary Stones – Top USMLE Diseases

Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. The kidneys can also be affected, and urate crystals can precipitate as chalkstone-like deposits (“tophi”) in the soft tissues, synovial tissues, or in bones near the joints. Hyperuricemia is due to overproduction and/or underexcretion of uric acid and is a necessary but insufficient precondition to developing urate crystal deposition disease (most hyperuricemic individuals never experience clinical gout). The most commonly involved joint is the first metatarsophalangeal joint. The identification of urate crystals in joint aspirate or tophi is diagnostic. Effective therapies to relieve the pain of a gout flare include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids; the choice of therapy depends on the individual and if there are any contraindications.

Nephrolithiasis is the formation of a stone, or calculus, caused by the precipitation of solutes in the urine anywhere along the urinary tract. The most common type of kidney stone is calcium oxalate; other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis presents with severe, colicky flank pain that often radiates to the groin, and hematuria due to ureteral damage. Diagnosis is made by noncontrast CT of the abdomen and pelvis or by renal ultrasound, and urinalysis is needed to exclude concomitant urinary tract infection (UTI). Management depends on the size of the stone. Small stones (< 5 mm) are likely to pass on their own and are managed expectantly with hydration and analgesics. Large stones unlikely to pass spontaneously are treated with extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy, or percutaneous nephrolithotomy. Nephrolithiasis can be complicated by hydronephrosis or acute pyelonephritis. Adequate hydration is the best prophylactic intervention to prevent kidney stones.

Purines and pyrimidines are heterocyclic aromatic compounds, which, along with sugar and phosphate groups, form the important components of nucleotides. Purines include adenine and guanine, while pyrimidines include thymine (in DNA), uracil (in RNA), and cytosine. Purine nucleotide synthesis follows a series of reactions using carbon donors, amino acids (e.g., glutamine, aspartate), and bicarbonate. The de novo pathway generates inosine monophosphate (IMP), which is the precursor of adenosine monophosphate (AMP) and guanosine monophosphate (GMP). Purine synthesis is regulated in the 1st 2 steps. Synthesis of pyrimidine nucleotides also follows different reactions, producing uridine monophosphate (UMP), which is converted to uridine triphosphate (UTP) and cytidine triphosphate (CTP). For thymine, a part of deoxyribonucleotides, ribonucleoside reductase is required to reduce the ribose moiety. Degradation of nucleotides result in xanthine then uric acid production in purines, while pyrimidines produce the amino acids, β-alanine, and β-aminobutyrate.

The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. The kidneys also play a major role in homeostatic processes, including electrolyte concentration, blood pressure, and acid–base regulation. Grossly, they consist of an outer cortex and inner medulla. Microscopic functional units known as nephrons filter the blood through a structure called the glomerulus, and this filtrate is then modified and concentrated as it moves through a complex tubular system. The renal arteries supply the kidneys via a central opening, known as the renal hilum, on its medial side; large renal veins empty directly into the vena cava.

Gout medications include antiinflammatory and urate-lowering medications. Colchicine is an antiinflammatory medication that can be used for acute gout flares. The urate-lowering drug classes include the xanthine oxidase inhibitors, uricosuric agents, and uricases. These medications are beneficial for the prevention of gout exacerbations and work through a variety of mechanisms. Xanthine oxidase inhibitors are the most commonly used urate-lowering therapy; these work by inhibiting the enzyme necessary for the conversion of purines to uric acid. Uricosuric agents reduce reabsorption of uric acid by the proximal tubule, thereby increasing renal excretion. Lastly, the urases are recombinant enzymes that metabolize uric acid to allantoin. In addition to gout, urate-lowering treatment can also be used for other indications, such as the prevention of tumor lysis syndrome and uric acid nephrolithiasis.

Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis presents with colicky flank pain, which radiates to the groin, and hematuria due to damage to the ureters. Diagnosis is made by noncontrast CT of the abdomen and pelvis or by renal ultrasound, and urinalysis is performed to exclude concomitant urinary tract infection (UTI). Management depends on the size of the stone. Small stones likely to pass on their own are managed conservatively with hydration and analgesics. Large stones unlikely to pass spontaneously are managed with extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy, or percutaneous nephrolithotomy. Nephrolithiasis can be complicated by hydronephrosis or acute pyelonephritis. Adequate hydration is the best prophylactic intervention to prevent kidney stones.

Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. The kidneys can also be affected, and urate crystals can precipitate as chalkstone-like deposits (“tophi”) in the soft tissues, synovial tissues, or in bones near the joints. Hyperuricemia is due to overproduction and/or underexcretion of uric acid and is a necessary but insufficient precondition to developing urate crystal deposition disease (most hyperuricemic individuals never experience clinical gout). The most commonly involved joint is the first metatarsophalangeal joint. The identification of urate crystals in joint aspirate or tophi is diagnostic. Effective therapies to relieve the pain of a gout flare include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids; the choice of therapy depends on the individual and if there are any contraindications.