Stones 2021 Flashcards
Incidence of kidney stones peaks in the ___________ decades of life.
Fourth to sixth
What is the concentration product?
A mathematical expression of the product of the concentrations of the pure chemical components (ions or molecules) of the salt.
What is the thermodynamic solubility product?
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.
Citrate: inhibitor MOA
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
Magnesium: inhibitor MOA
Complexation with oxalate, which reduces ionic oxalate concentration and calcium oxalate supersaturation
Nephrocalcin: inhibitor MOA
- Strongly inhibits the growth of calcium oxalate monohydrate crystals
- Inhibit nucleation and aggregation of calcium oxalate crystals
Tamm-Horsfall protein: inhibitor MOA
- MOST ABUNDANT PROTEIN in urine
- Potent inhibitor of calcium oxalate monohydrate crystal aggregation, but not growth
Osteopontin/uropontin: inhibitor MOA
Inhibit nucleation, growth, and aggregation of calcium oxalate crystals, as well as to reduce binding of crystals to renal epithelial cells in vitro
Bikunin: inhibitor MOA
Strong inhibitor of calcium oxalate crystallization, aggregation, and growth in vitro
What is the matrix in renal calculi?
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.
What percent of dietary Ca is absorbed in the intestine?
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
Most POTENT stimulator of intestinal Ca absorption
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
Calcitriol acts on the ____ and ____, in addition to its action in increasing intestinal calcium absorption.
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
PTH action on the bone and kidneys
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
Primary regulator of renal phosphate handling
Regulation of renal phosphate handling is primarily by way of PTH, which inhibits renal tubular reabsorption of filtered phosphate.
Oxalate is absorbed in the _______
Oxalate absorption occurs throughout the intestinal tract, with about half or more occurring in the small intestine and half in the colon.
Most potent oxalate-degrading bacterium
Oxalibacter formigenes
Most common component of urinary calculi
Calcium: a major constituent of nearly 80% of stones
Most common abnormality in calcium stone formers
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
What are the types of hypercalciuria?
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
Malignancy-related hypercalcemia
Tumors in patients with humoral hypercalcemia produce a PTH-related protein (PTHrP).
Like PTH, PTHrP increases renal calcium absorption and stimulates osteoblasts
Hyperoxaluria
Urinary oxalate greater than 40 mg/day, leads to increased urinary saturation of calcium oxalate and subse- quent promotion of calcium oxalate stones
Primary hyperoxaluria
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
Enteric hyperoxaluria
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
Dietary hyperoxaluria
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
Hyperuricosuria
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!
Hypocitraturia
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
Causes of hypocitraturia
Pathologic states associated with ACIDOSIS:
- Distal RTA
- Chronic diarrheal states
- Excess animal protein
- Diuretics
- ACE
- Strenuous exercise - lactic acidosis
RTA
Metabolic acidosis resulting from defects in renal tubular hydrogen ion secretion or bicarbonate reabsorption
Type 1 (distal) RTA
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
Type 2 (proximal) RTA
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
Type 4 (distal) RTA
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
Hypomagnesiuria
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
Uric acid stone formation: LOW or HIGH pH?
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
Three main determinants of URIC ACID stone formation
Low urine pH
Low urine volume
Hyperuricosuria
Infection stones are primarily composed of ______ and _____.
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)
Struvite stones (MAP) occur only with infection by _____
Urea-splitting bacteria
Most common urease-producing pathogens (4)
Proteus Klebsiella Pseudomonas Staphylococcus E. coli: only rare species produce urease
Most common organism associated with infection stones
Proteus mirabilis
TRUE or FALSE: Struvite stones are more common in women than men
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
Ammonium urate stones
Radiolucent!
Patients with chronic diarrhea, inflammatory bowel disease, ileostomy bowel diversions, laxative abuse, recurrent urinary tract infection, and recurrent uric acid stone formation
Renal stones in pregnancy
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.
