Which of the following is CORRECT regarding the nephron?
Answer B
The glomerulus, which is about 200 μm in diameter, is formed by the invagination of a tuft of capillaries into the dilated, blind end of the nephron. In the distal convoluted tubule, while the predominant principle cells (P) are involved in Na+ reabsorption and vasopressin-stimulated water reabsorption, the intercalated cells (I) are associated with acid secretion and HCO3 − transport. It is the wall of the afferent arteriole that contains renin-secreting juxtaglomerular cells. At this point the wall of the tubular epithelium is modified histologically to become the macula densa. The juxtaglomerular cells, the macula densa and the lacis cells near them are collectively known as juxtaglomerular apparatus. The kidney receives 25% of cardiac output.
Which of the following is CORRECT regarding GFR?
Answer A
The 24-hour creatinine clearance (CrCl) overestimates true GFR by 10%–20% and thus as GFR declines, tubular secretion increases in response to increasing creatinine levels may contribute upto 35% of all creatinine levels at GFR levels of 40–80 mL/min. At best, then, the CrCL should be considered the ‘upper limit’ of the true GFR. Cockcroft-Gault measures creatinine clearance by the formula − CrCl = {[(140-age) × (Lean Body Weight in kg)]/[Serum Creatinine (mg/dL) × 72]} × 0.85 (women). It underestimates CrCL in children due to reabsorption. Moreover, the calculation is dependent on accurate collection of the specimen, which can be incomplete. The MDRD formula to estimate GFR is eGFR (in mL/min/1.73 m) = 186 × (Serum Creatinine [mg/dL])−1.154 × (age)−0.203 × (0.742 if female) × (1.210 if African American). However, this formula is not validated for use in children, whilst Cockcroft-Gault formula overestimates CrCl in children due to reabsorption.
Which of the following is TRUE regarding bone mineralisation?
Normal regulation of bone mineralisation occurs through maintenance of serum calcium and phosphorus levels and is achieved through the actions of vitamin D and parathyroid hormone (PTH). The actions of both hormones are exerted largely through the kidney. Vitamin D3, which has minimal biological activity, requires two hydroxylations – first occurs in the liver and the second within the tubular cell, through the action of 25-hydroxylase to form 25-hydroxycholecalciferol (calcidiol). The calcidiol is then transported to the kidney, where it is filtered and reabsorbed by renal tubular cells. These cells contain both 1α-hydroxylase and 24α-hydroxylase, and produce either the active 1,25-dihydroxycholecalciferol (calcitriol) or the inactive 24,25-dihydroxycholecalciferol. Parathormone increases the active calcium reabsorption at the level of the distal tubule. Secondly, it decreases phosphate reabsorption in the proximal convoluted tubule (and the distal tubule, to a lesser degree) and thirdly, it stimulates calcitriol production by increasing 1α-hydoxylase levels and decreasing 24α-hydroxylase levels.
Which of the following is TRUE in unilateral ureteric obstruction (UUO)?
Answer D
In UUO, RBF increases during the first 0–90 minutes and is accompanied by a high collecting system pressure because of the obstruction. In the second phase lasting up to 5 hours, both RBF and collecting system pressure remain elevated but RBF begins to gradually decline. A third phase beginning about 5 hours after obstruction is characterised by a further decline in RBF, now paralleled by a decrease in collecting system pressure.
Infusion of the angiotensin-converting enzyme (ACE) inhibitor Captopril attenuates the declines in RBF and GFR in UUO, suggesting that angiotensin II is an important mediator of the preglomerular vasoconstriction in the second and third phases of UUO. Endothelin antagonists limit the reduction of RBF and GFR in rats during and after release of UUO.
Regarding ureteric obstruction (n unilateral ureteric obstruction UUO), which is CORRECT?
Answer E
In UUO, both PGE2 and NO contribute to the net renal vasodilation that occurs early following UUO. Studies have shown that the increase in PGE2 and the vasodilation of the obstructed kidney is blocked by indomethacin, a prostaglandin synthesis inhibitor. TXA2 is an influential postobstructive vasoconstrictor that contributes to the continued reduction in GFR and RBF. Administration of TXA2 synthesis inhibitors to the obstructed kidney limits the reduction in RBF and GFR.
In contrast to the early robust renal vasodilation with UUO, there is a modest increase in RBF with BUO that lasts approximately 90 minutes, followed by a prolonged and profound decrease in RBF that is greater than found with UUO. The shift seen with UUO of blood flow from outer to inner cortex is the opposite of that with BUO.
This difference between BUO and UUO could be due to an accumulation of vasoactive substances like ANP in BUO and this could contribute to preglomerular vasodilation and postglomerular vasoconstriction. Such substances do not accumulate in UUO because they would be excreted by the contralateral kidney.
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