Stones 2021

Question 1

Incidence of kidney stones peaks in the ___________ decades of life.

Answer 1

Fourth to sixth

Question 2

What is the concentration product?

Answer 2

A mathematical expression of the product of the concentrations of the pure chemical components (ions or molecules) of the salt.

Question 3

What is the thermodynamic solubility product?

Answer 3

The point at which the dissolved and crystalline components are in equilibrium for a specific set of conditions.

Addition of further crystals to the saturated solution will cause the crystals to precipitate unless the conditions of the solution, such as pH or temperature, are changed.

Question 4

Citrate: inhibitor MOA

Answer 4

Inhibits calcium oxalate and calcium phosphate stone formation:

• Complexes with calcium, thereby reducing the availability of ionic calcium to interact with oxalate or phosphate
• Directly inhibits the spontaneous precipitation of calcium oxalate
• citrate prevents heterogeneous nucleation of calcium oxalate by monosodium urate

Question 5

Magnesium: inhibitor MOA

Answer 5

Complexation with oxalate, which reduces ionic oxalate concentration and calcium oxalate supersaturation

Question 6

Nephrocalcin: inhibitor MOA

Answer 6

• Strongly inhibits the growth of calcium oxalate monohydrate crystals
• Inhibit nucleation and aggregation of calcium oxalate crystals

Question 7

Tamm-Horsfall protein: inhibitor MOA

Answer 7

• MOST ABUNDANT PROTEIN in urine

- Potent inhibitor of calcium oxalate monohydrate crystal aggregation, but not growth

Question 8

Osteopontin/uropontin: inhibitor MOA

Answer 8

Inhibit nucleation, growth, and aggregation of calcium oxalate crystals, as well as to reduce binding of crystals to renal epithelial cells in vitro

Question 9

Bikunin: inhibitor MOA

Answer 9

Strong inhibitor of calcium oxalate crystallization, aggregation, and growth in vitro

Question 10

What is the matrix in renal calculi?

Answer 10

Renal calculi consist of crystalline and noncrystalline components. The noncrystalline component is termed matrix, which typically accounts for about 2.5% of the weight of the stone.

Composed of a combination of mucoproteins, proteins, carbohydrates, and urinary inhibitors.

Question 11

What percent of dietary Ca is absorbed in the intestine?

Answer 11

Between 30% and 40% of dietary calcium is absorbed from the intestine, with MOST being absorbed in the small intestine and only approximately 10% absorbed in the colon

Question 12

Most POTENT stimulator of intestinal Ca absorption

Answer 12

CALCITRIOL 1,25(OH)2D3 - Active form of vitamin D

Decrease in serum Ca –> PTH secretion –> conversion of 25-hydroxyvitamin D3 to calcitriol –> enhancement of Ca absorption

Question 13

Calcitriol acts on the ____ and ____, in addition to its action in increasing intestinal calcium absorption.

Answer 13

Bone: along with PTH, promotes the recruitment and differentiation of osteoclasts that subsequently mobilize calcium from the bone.

Kidney: Calcitriol modulates parathyroid function by inhibiting synthesis of PTH through enhanced vitamin D receptor and calcium- sensing receptor (CaSR) expression in the parathyroid glands –> PTH increases renal Ca reabsorption and enhances phosphate secretion

Question 14

PTH action on the bone and kidneys

Answer 14

PTH: stimulates mobilization of calcium from bone through the action of osteoclasts, further raising serum calcium and phosphorus.

Kidneys: enhances renal calcium reabsorption and reduces renal tubular reabsorption of phosphate

Question 15

Primary regulator of renal phosphate handling

Answer 15

Regulation of renal phosphate handling is primarily by way of PTH, which inhibits renal tubular reabsorption of filtered phosphate.

Question 16

Oxalate is absorbed in the _______

Answer 16

Oxalate absorption occurs throughout the intestinal tract, with about half or more occurring in the small intestine and half in the colon.

Question 17

Most potent oxalate-degrading bacterium

Answer 17

Oxalibacter formigenes

Question 18

Most common component of urinary calculi

Answer 18

Calcium: a major constituent of nearly 80% of stones

Question 19

Most common abnormality in calcium stone formers

Answer 19

Hypercalciuria:

• Greater than 200 mg of urinary calcium/day after adherence to a 400-mg calcium, 100-mg sodium diet for 1 week
• Greater than 4 mg/kg/day or greater than 7 mmol/ day in men and 6 mmol/day in women

Question 20

What are the types of hypercalciuria?

Answer 20

ABSORPTIVE: Increased intestinal absorption of Ca –> transient increase in serm CA –> suppressed PTH –> increased renal filtration of Ca –> hypercalciuria

RENAL: Impaired renal tubular reabsorption –> elevated urinary Ca –> secondary hyperparathyroidism (serum Ca levels remain normal)

RESORPTIVE: Primary hyperparathyroidism (parathyroid adenoma) –> excess PTH –> excess bone resoprtion –> increase renal calcitriol –> enhanced intestinal absorption of calcium –> elevated serum and urine Ca and reduced Phos levels

Question 21

Malignancy-related hypercalcemia

Answer 21

Tumors in patients with humoral hypercalcemia produce a PTH-related protein (PTHrP).

Like PTH, PTHrP increases renal calcium absorption and stimulates osteoblasts

Question 22

Hyperoxaluria

Answer 22

Urinary oxalate greater than 40 mg/day, leads to increased urinary saturation of calcium oxalate and subse- quent promotion of calcium oxalate stones

Question 23

Primary hyperoxaluria

Answer 23

Autosomal recessive inherited disorders in glyoxylate metabolism by which the normal conversion of glyoxylate to glycine is prevented, leading to preferential oxidative conversion of glyoxylate to oxalate, an end product of metabolism

Question 24

Enteric hyperoxaluria

Answer 24

Most common cause of acquired hyperoxaluria

Chronic diarrheal states –> fat malabsorption results in saponification of fatty acids with divalent cations such as Ca and Mg –> reduced CaOx complexation –> increased pool of oxalate for reabsorption

Question 25

Dietary hyperoxaluria

Answer 25

Overindulgence in oxalate-rich food: nuts, chocolate, brewed tea, spinach, potatoes, beets, rhubarb Severe Ca restriction --> reduced intestinal binding of oxalate, increased intestinal oxalate absorption

Question 26

Hyperuricosuria

Answer 26

Urinary uric acid >600mg/day Increases levels of monosodium urate --> promote CaOx crystallization through heterogenous nucleation or epitaxial crystal growth Sodium urate: adsorbs inhibitors of crystallization!

Question 27

Hypocitraturia

Answer 27

Urinary citrate <320mg/day Acid-base state = primary determinant of urinary citrate excretion Metabolic acidosis: reduces citrate levels secondary to enhanced renal tubular reabsorption and decreased synthesis of citrate in peritubular cells

Question 28

Causes of hypocitraturia

Answer 28

Pathologic states associated with ACIDOSIS: - Distal RTA - Chronic diarrheal states - Excess animal protein - Diuretics - ACE - Strenuous exercise - lactic acidosis

Question 29

RTA

Answer 29

Metabolic acidosis resulting from defects in renal tubular hydrogen ion secretion or bicarbonate reabsorption

Question 30

Type 1 (distal) RTA

Answer 30

Most common form of RTA , associated with STONE FORMATION Dysfunction of the α-type intercalated cells, which secrete protons into the urine via an apical H+-ATPase --> failure to acidify urine HYPERCALCIURIA HYPOCITRATURIA INC. URINARY pH CALCIUM PHOSPHATE most comon

Question 31

Type 2 (proximal) RTA

Answer 31

Defect in HCO3− reabsorption associated with initial high urine pH that normalizes as plasma HCO3− decreases and the amount of filtered HCO3− falls --> bicarbonaturia --> reduced net acid excretion + metabolic acidosis Stones: UNCOMMON because of normal urinary citrate excretion

Question 32

Type 4 (distal) RTA

Answer 32

Associated with chronic renal damage: usually in interstitial renal disease and diabetic nephropathy. Reduced glomerular filtration --> hyperkalemic hyperchloremic met acidosis Can still generate acidic urine in response to acid challenge

Question 33

Hypomagnesiuria

Answer 33

Magnesium complexes with oxalate and calcium salts, and therefore low magnesium levels result in reduced inhibitory activity. Low urinary magnesium is also associated with decreased urinary citrate levels, which may further contribute to stone formation

Question 34

Uric acid stone formation: LOW or HIGH pH?

Answer 34

LOW urine pH is thought to be a risk factor for uric acid, calcium oxalate, and mixed calcium and uric acid stones. At pH 5, even modest amounts of uric acid exceed uric acid solubility

Question 35

Three main determinants of URIC ACID stone formation

Answer 35

Low urine pH Low urine volume Hyperuricosuria

Question 36

Infection stones are primarily composed of ______ and _____.

Answer 36

Infection stones are composed primarily of magnesium ammonium phosphate hexahydrate (MgNH4PO4 • 6H2O) but may in addition contain calcium phosphate in the form of carbonate apatite (Ca10[PO4]6 • CO3)

Question 37

Struvite stones (MAP) occur only with infection by _____

Answer 37

Urea-splitting bacteria

Question 38

Most common urease-producing pathogens (4)

Answer 38

``` Proteus Klebsiella Pseudomonas Staphylococcus E. coli: only rare species produce urease ```

Question 39

Most common organism associated with infection stones

Answer 39

Proteus mirabilis

Question 40

TRUE or FALSE: Struvite stones are more common in women than men

Answer 40

TRUE. Because infection stones occur most commonly in those prone to frequent urinary tract infections, struvite stones occur more often in women than men by a ratio of 2 : 1

Question 41

Ammonium urate stones

Answer 41

Radiolucent! Patients with chronic diarrhea, inflammatory bowel disease, ileostomy bowel diversions, laxative abuse, recurrent urinary tract infection, and recurrent uric acid stone formation

Question 42

Renal stones in pregnancy

Answer 42

Renal blood flow increases, leading to a 30% to 50% rise in glomerular filtration rate, which subsequently increases the filtered loads of calcium, sodium, and uric acid.