Stones: Etiology, Epi, And Pathogenesis

Front 1

What is the prevalence of stone disease in the United States, and is this increasing or decreasing?

Is there a racial or gender bias to stone disease?

Back 1

- It has been estimated at 10-15% of the population, and is increasing (3.8% in 1976 to 5.2% in 1994)

- Previous studies showed M > F by two to three times, but this may be narrowing. ¬
- Whites > Hispanics (70%) > Asians (63%) > African Americans (44%) prevalence of whites.)

Front 2

Define the terms undersaturated, metastable, unstable in relation to states of solute saturation in urine. Can metastable urine form stones?

Back 2

- Undersaturated- stones will not form under any circumstances.
- Metastable- urine whose solute is past the point of its thermodynamic solubility product but crystal precipitation or stone formation isn’t occuring. This can be due to inhibitors.
- Unstable- urine has reached the formation product and is forming stones
- Stones can form in metastable urine if increased transit time through the nephron secondary to stasis or obstruction, or by a process known as heterogeneous nucleation (i.e. not a pure solution)

Front 3

Name the molecules or proteins known to be inhibitors of stone formation?

Back 3

- Magnesium, citrate, Nephrocalcin, Tamm-Horsfall mucoprotein (inhibits aggregation, NOT growth), Uropontin

Front 4

. Is calcium or oxalate concentration more important for the formation of calcium oxalate stones? Explain the role of citrate in the formation of calcium oxalate and calcium phosphate stones?

Back 4

- Trick question, they are equally important (Pak et al, 2004)
- Citrate reduces calcium availability by binding calcium complexes. It acts as an inhibitor of calcium oxalate and calcium phosphate stone formation.

Front 5

What are Randall’s plaques and how are they involved in the pathogenesis of stone formation? How do patients with enteric hyperoxaluria differ?

Back 5

- Soft tissue calcifications of calcium apatite found in deep renal medulla skirting the surface of the epithelium of the papilla, where they act as nucleating elements for renal calculi or stones. They originate on the basement membrane of the cells of the thin limbs of the loops of Henle. Plaques erode through these cells into the subepithelium medullary interstitium. They eventually erode through the urothelium and serve as nidus for stone formation.

- Hyperoxaluric stone formers don’t have plaques, but instead have apatite crystals deposits plugging the lumens of the terminal collecting ducts with associated inflammation and fibrosis of the interstitium.

Front 6

Why does Davis order a serum calcium, and if elevated then a PTH and 1,25-Dihydroxyvitamin D3?

Does PTH have any direct effect on intestinal absorption of calcium?

Back 6

- Calcium absorption occurs mainly in small intestine, dependent on calcium intake.
- PTH enhances proximal tubular reabsorption of calcium and renal phosphate excretion
- 1,25 (OH)D3 is the most potent stimulator of intestinal calcium absorption
- PTH stimulates 1-alpha hydroxylase in the proximal tubule of the kidney to convert 25-dihydroxyvitamin D to 1,25 (OH)2D3.

--NO

Front 7

T/F: Most of the oxalate that our kidneys excrete comes from our diet.

Back 7

- False. Approximately 80% is endogenously produced.

Front 8

List the most common composition of stones and their relative occurrence.

Back 8

- Calcium oxalate – 60%
- Calcium oxalate and hydroxyapatite – 20%
- Brushite stones – 2%
- Uric acid – 7%
- Struvite – 7%
- Cystine – 1-3%
- Medication bi-product stones (Triamterene, adenosine, silica, indinavir, ephedrine) – rare

Front 9

Identify the most common metabolic abnormality identified on 24 hour urine collection in calcium stone formers? The three pathophysiological abnormalities that cause it?

Back 9

- Hypercalciuria
- Absorptive, renal, and resorptive hypercalciuria

Front 10

Define absorptive hypercalciuria (AH), and specifically the difference between type I and type II? Explain how serum calcium can be normal in these patients if absorption of calcium is increased?

Back 10

- AH: increased urinary calcium excretion after an oral calcium load, > 0.2mg/mg cr. Fasting urinary calcium is usually normal, although may be elevated. The underlying abnormality is increased intestinal absorption of calcium.
- Type 1: high urinary calcium despite restricted calcium diet
- Type II: will normalize their urinary calcium with a restricted calcium diet.
- With increased absorption there is a transient increase in the serum calcium. This suppresses the level of PTH, which causes an increase in renal filtration (urinary excretion) of calcium. This explains the normal serum calcium and elevated urine calcium levels.

Front 11

Define Renal Hypercalciuria. Differentiate this from absorptive hypercalciuria

Back 11

- High fasting urinary calcium levels (>.11 mg/dl glomerular filtration) with normal serum calcium.
- Impaired renal tubular reabsorption of calcium leads to elevated urinary calcium levels leading to secondary hyperparathyroidism.

Front 12

What is usually the cause of Resorptive Hypercalciuria and what serum and urine levels are to be expected?

Back 12

- caused by primary hyperparathyroidism usually caused by a parathyroid adenoma.
- increased serum calcium
- increased urinary calcium
- decreased serum phosphate

Front 13

What if you are suspicious for resorptive hypercalciuria but the patient has a normal serum calcium level?

Back 13

- Give a thiazide diuretic. It should exacerbate the hypercalcemia.

Front 14

What is primary hyperoxaluria? What happens if it is not treated, and what is the treatment?

Back 14

- rare AR disorder in glyoxylate metabolism which converts glycoxylate to oxalate instead of glycine. This results in increased urinary oxalate, increased stone formation.
- ESRD by age 15 in 50% with 30% mortality. Treat with liver-kidney transplant.

Front 15

How is this different that acquired hyperoxaluria?

Back 15

- associated with chronic diarrheal states
- chronically dehydrated, decreased K+, decreased Mg, hypocitraturia, decreased urine pH, all of which increase risk of stone formation.

Front 16

What foods are high in oxalate? What other dietary factors affect oxalate absorption?

Back 16

- sweet potatoes, chocolate, tea, spinach/legumes, nuts, broccoli, strawberries
- Calcium restriction, increased animal fats/proteins (purines), Vitamin C supplementation can all be converted to oxalate.

Front 17

. Can granulomatous diseases like sarcoid cause hypercalciuric stone disease? Treatment?

Back 17

- increased vitamin D from lymph nodes and pulmonary alveolar cells leads to hypercalcemia, hypercalciuria, but decreased PTH
- Treat with corticosteroids to resolve hypercalcemia

Front 18

What causes hyperuricosuria and how does it promote stone formation?

Back 18

- caused by increased dietary purine intake. Also gout, myeloproliferative/lymphoproliferative, multiple myeloma, pernicious anemia, hemoglobinopathies, thalessemia
- increased urinary urate = increased monosodium urate which promotes calcium oxalate stones. If pH < 5.5, form uric acid, calcium oxalate, or both. If ph > 5.5, calcium oxalate will form.

Front 19

How are citrate levels affected by metabolic acidosis?

Back 19

- met acidosis decrease urinary citrate levels secondary to increase renal tubular reabsorption and decrease citrate synthesis in peritubular cells

Front 20

Describe Renal Tubular Acidosis. What type is of particular importance to Urologists?

Back 20

- clinical syndrome characterized by metabolic acidosis resulting from defects in renal tubular hydrogen ion secretion and urinary acidification. Types 1, 2, 4.
- Type 1 (distal) RTA is the most common, and the most frequently associated with stone formation. Characterized by inability to acidify urine during systemic acidosis secondary to abnormal hydrogen ATPase.

Front 21

How can you recognize this clinically?

Back 21

- Hypokalemic, hyperchloremic, non-ion gap metabolic acidosis. Nephrolithiasis, nephrocalcinosis with urine pH greater than 6.
- Calcium phosphate stones secondary to hypercalciuria, hypocitraturia, and increased urine pH.

Front 22

What is the pKa of Uric Acid?

What is the most important factor in uric acid stone formation?

Back 22

- 5.35 (Coward M, et al)

- decreased urine pH (<pKa of uric acid). Also impacted by low urine volume and hyperuricosuria.

Front 23

What percentage of stones in children are cystine? What causes them?

Back 23

- 10%. Cysteinuria is an AR defect causing decreased amino acid absorption including cysteine, ornithine, lysine, arginine. Cystine’s poor solubility leads to stone formation.

Front 24

How do infection stones form? What are the most common pathogens?
What percentage of all stones are infection stones?

Back 24

-Urea is normally found in urine. Certain bacteria (proteus, kelbsiella, pseudomonas, staphlycoccus) split urea into ammonia and carbon dioxide. This facilitates an alkaline environment that helps convert ammonia to ammonium. The bacteria keep producing ammonia, and the process continues as the urine continues to become basic. Proteus Mirabilis is the most common organism associated with infection stones.

- 5-15%.

Front 25

How are bacteria are involved in stone formation?

Back 25

- Damage to the mucosal layer causing increased bacterial colonization and crystal adherence
- Ammonium, produced by urea splitting organisms, may alter the GAG layer
- Altering the activity of urokinase and sialidases. E. Coli are thought to be associated with stone production in this regard.

Front 26

What are xanthine stones?

Back 26

- rare stone type due to defect in enzyme that converts xanthine to uric acid. Often confused with uric acid stones because both are radiolucent.
- Allopurinol at high levels is a rare cause of xanthine stones in patients with Lesch-Nyhan or those being treated for uric acid stones.

Front 27

What are the risk factors for developing ammonium acid urate stones?

Back 27

- Laxative abuse, recurrent UTI, recurrent uric acid stones, IBD, ileostomy after total colectomy (colon normally absorbs oxalate)

Front 28

What is the incidence of stone formation in patients with UPJ? Is this purely a functional problem? What other anatomic abnormalities increase the risk of stone formation?

Back 28

- 20%. Studies have emphasized the role of underlying metabolic abnormalities in the etiology of renal calculi in patients with UPJ obstruction.
- Caliceal Diverticula, but functional versus role of an underlying metabolic problem remains unclear.

Front 29

Describe the changes during pregnancy that change urinary stone risk.

Back 29

- Increased renal blood flow with increased GFR leading to rise in filtered loads of calcium, sodium, and uric acid
- pregnant women have also been shown to excrete increased amounts of inhibitors like citrate, magnesium, and glycoproteins