Question 2

College Answer

This question was well answered by most candidates. The description of renal flow involves a brief comment of the anatomy including interlobar, arcuate, interlobular arteries, then afferent and efferent arterioles – 2 sets of capillaries and then corresponding veins and better answers made the distinction better cortical and medullary flow and went on to detail the consequence of this. Renal blood flow is autoregulated and most candidates describe well the various mechanisms around myogenic and tubuloglomerular feedback. Additional marks were gained with by discussing renal vascular resistance and how this may be varied. The impact of adrenoreceptor agonists is varied but generally sympathomimetic agents will vasoconstrict and therefore increase renovascular resistance and result in a decrease renal blood flow. The relative impact on afferent vs efferent arteriolar tone may alter glomerular perfusion pressure.

Discussion

• Renal blood flow
  • Total blood flow: 20-25% of cardiac output, or 1000ml/min, or 400ml/100g/min
    • 95% goes to the cortex, 5% goes to the medulla
    • Medullary blood flow must remain low to maintain the urea concentration gradient, to facilitate the concentration of urine
  • Total renal blood is high for reasons of filtration rather than metabolism
  • Total renal oxygen extraction is low (10-15%)
  • Renal oxygen extraction remains stable as renal blood flow changes, because renal metabolic rate depends on glomerular filtration rate and tubular sodium delivery
• Autoregulation of renal blood flow
  • Renal blood flow remains constant over a MAP range of 75-160 mmHg
  • This regulation is produced by:
    • Myogenic response (50% of the total autoregulatory response)
    • Tubuloglomerular feedback (35%)
    • Other mechanisms involving angiotensin-II and NO (<15%)
  • Intrinsic myogenic mechanisms:
    • Vasoconstriction in response to wall stretch
    • This is a stereotyped vascular smooth muscle response, not unique to the kidney
  • Tubuloglomerular feedback
    • This is a negative feedback loop which decreases renal blood in response to increased sodium delivery to the tubule
    • The mechanism is mediated by ATP and adenosine secreted by macula densa cells, which cause afferent arteriolar vasoconstriction
• Effect of adrenoceptor agonists on renal blood flow
  • Sympathetic tone regulates the range of renal blood flow autoregulation
  • Massive sympathetic stimulus (eg. shock) overrides autoregulation and markedly decreases renal blood flow
  • Glomerular filtration rate is less affected (out of proportion to blood flow) because the efferent arterioles vasoconstrict more than the afferent in response to a sympathetic stimulus.
  • This is mediated by adrenoceptors (mainly α₁)
  • Ergo, α-adrenoceptor agonists will act as renal vasoconstrictors and decrease renal blood flow (and, slightly, glomerular filtration)
  • Juxtaglomerular cells of the kidney also have β₁ receptors

Just, Armin. "Mechanisms of renal blood flow autoregulation: dynamics and contributions." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292.1 (2007): R1-R17.

Stein, Jay H. "Regulation of the renal circulation." Kidney international 38.4 (1990): 571-576.

Bertram, John F. "Structure of the renal circulation." Advances in Organ Biology Volume 9, 2000, Pages 1-16 (2000)

Kriz, Wilhelm, and Brigitte Kaissling. "Structural organization of the mammalian kidney." The kidney: physiology and pathophysiology 3 (1992): 587-654.

Braam B., Yip S., Cupples W.A. (2014) Anatomy, Physiology, and Pathophysiology of Renal Circulation. In: Lanzer P. (eds) PanVascular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37393-0_146-1