Question 21

College Answer

A good answer required mentioning factors that affect systemic oxygen capacity and delivery (eg 
Hb, cardiac output, PaO2, etc), Hb-HBO2 dissociation and a description of the anatomy and 
regulation of renal medullary blood flow. 20 – 30% of nephrons have glomeruli deep in the cortex 
and long Loop of Henle that go deep into medulla. Here blood supply differs – long efferent 
arterioles from glomeruli into outer medulla and inner cortex that then divide into vasa recta deep 
in medulla. These vessels carry post glomerular blood so have less serum, mostly plasma, ie 
more viscous and concentrated. Factors that influence medullary blood flow include: 
Sympathetic stimulation – decrease (via efferent arteriolar constriction), Angiotensin II (via 
tubuloglomerular feedback) – decrease (via efferent arteriolar constriction), Endothelin – 
decrease (via efferent arteriolar constriction), Prostaglandins – increase, Bradykinin – increase, 
high protein meal – increase, high glucose levels – increase. Candidates performed poorly due to 
a lack of knowledge of the topic and/or failure to logically present their answer. Common 
mistakes were to give no value for renal blood flow, to discuss the function of the medulla which 
was not required and to not describe the factors that influence medullary blood flow. 

Discussion

The examiners chose to ask this question in a weird roundabout way here, by phrasing it in terms of oxygen delivery to the medulla.   This wording will probably have led 96% of the candidates to assume that the physiological and anatomical factors determining renal medullary blood flow were being asked about. To discuss the oxygen content of whole blood and cardiac output would not have occurred to most people, as of course the kidney has little to do with them, and those people would have lost marks.

Functional anatomy:

• Efferent arterioles drain blood from the glomerulus; 
  • Cortical nephron efferent arterioles branch into peritubular capillaries
  • Juxtaglomerular nephron efferent arteroles branch into vasa recta
• Peritubular capillaries:
  • Thin-walled fenestrated capillaries, similar to systemic capillaries
  • Surround the proximal convoluted tubule and distal convoluted tubule
  • Main role is reabsorption and active secretion of solutes
• Vasa recta:
  • Main role is concentration of urine
  • Descending vasa recta: mainly involved in countercurrent mechanism
  • Ascending vasa recta: mainly involved in reclaiming reabsorbed water from the medulla

Factors that influence oxygen delivery and blood flow to the medulla:

• Distribution of blood flow in the kidney:
  • 95% of blood flow goes to the cortex, 5% goes to the medulla
• Oxygen-carrying capacity of the blood:
  •  (sO₂ × ceHb × BO₂ ) + (PaO₂ × 0.03)
• Cardiac output:
  • CO = HR ×  SV
• Regulatory factors affecting renal microcirculation:
  • Sympathetic tone: vasoconstricts efferent arterioles
  • Humoural factors
    • ​​​​Vasoconstrictor stimuli:
      • Angiotensin II
      • Endothelin
    • Vasodilator stimuli:
      • Prostaglandins 
      • Bradykinin 
      • high protein meal
      • hyperglycaemia
  • Autoregulatory mechanisms:
    • Myogenic response (50% of the total autoregulatory response)
      • Vasoconstriction in response to wall stretch
      • This is a stereotyped vascular smooth muscle response, not unique to the kidney
    • Tubuloglomerular feedback (35%)
      • 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
    • 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

Pallone, Thomas L., Zhong Zhang, and Kristie Rhinehart. "Physiology of the renal medullary microcirculation." American Journal of Physiology-Renal Physiology 284.2 (2003): F253-F266.

Zimmerhackl, Bernd, Channing R. Robertson, and Rex L. Jamison. "The microcirculation of the renal medulla." Circulation research 57.5 (1985): 657-667.