Question 6

Describe the physiology of the Renin and Angiotensin system.

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College Answer

Renin and angiotensin are core components in the regulation of plasma volume and blood 
pressure regulation. It is unfortunate that many candidates presenting to this examination are not 
able to provide sufficient information for a pass. For a good answer, candidates were expected to 
mention what renin and angiotensin are and what they do, as well as briefly mention the place of 
angiotensin converting enzyme (converts Angiotensin I to Angiotensin II and inactivates 
bradykinin). Renin is a proteolytic enzyme cleaves angiotensinogen to angiotensin I, secreted by 
the juxtaglomerular cells of the kidney which are located in media of afferent arteriole and in 
close proximity to the glomerulus and the distal convoluted tubule (macula densa). Angiotensin II 
acts on cell surface AT1 and AT2 receptors. Major functions being to preserve of GFR & 
enhanced Na/H2O reabsorption in the setting of reduced renal blood flow (candidates expected to 
outline the mechanism by which this occurs), vasoconstriction, stimulate aldosterone secretion 
and increase thirst and ADH secretion. The better candidates also mentioned that it decreases 
sensitivity of baroreceptor reflex, increases secretion of ACTH and facilitates noradrenaline 
release from sympathetic nervous system as well as its fate (metabolized by blood/tissue 
peptidases). A good response for regulation would have been mentioning principally regulated 
via renin release (which in itself is influenced by renal sympathetic nervous system activity, 
intrarenal baroreceptors and macula densa sodium chloride delivery, ADH and intra-renal 
prostaglandins), negative feedback from angiotensin II.

Recommended sources: Textbook of medical Physiology, Guyton, Chp 26


There is no mention of whether a diagram might have been useful, but in the author's opinion they are always useful. Thus:

extremely simplified diagram of RAAS

In the form of verbiage:

  • Stimulus: hypotension, hypovolemia, salt depletion, renal hypoperfusion
  • Sensor:
    • arterial and renal baroreceptors
    • β-1 receptors on the juxtaglomerular cells
  • Afferent: glossopharyngeal and vagus nerves, renal sensors (macula densa)
  • Efferent: enzymatic steps:
    • Renin 
      • 37 kDa enzyme 
      • Released from juxtaglomerular cells
      • Is the rate-limiting step
      • Cleaves angiotensiongen into angiotensin-I
    • ACE
      • Pulmonary enzyme
      • Cleaves angiotensin-I into angiotensin-II
    • Angiotensin-II
      • Increases Na+/H+ exchange in the proximal tubules, thus sodium retention and acid excretion
      • Increases sensation of thirst
      • Increases sensitivity to catecholamines
      • Stimulates the release of vasopressin
      • Stimulates the release of aldosterone
    • Vasopressin and aldosterone
      • Produce more vasoconstriction as well as more salt and water retention
  • Effectors:
    • A2 receptors, adrenal glomerulosa, pituitary gland, renal tubule
  • Effect: vasoconstriction of peripheral circulation and the increase in body fluid volume


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Fyhrquist, Frej, and Outi Saijonmaa. "Renin‐angiotensin system revisited." Journal of internal medicine 264.3 (2008): 224-236.

Persson, Pontus B. "Renin: origin, secretion and synthesis." The Journal of physiology 552.3 (2003): 667-671.

Lu, Hong, et al. "Structure and functions of angiotensinogen." Hypertension Research 39.7 (2016): 492-500.

Coates, David. "The angiotensin converting enzyme (ACE)." The international journal of biochemistry & cell biology 35.6 (2003): 769-773.

Busse, Laurence W., et al. "The effect of angiotensin II on blood pressure in patients with circulatory shock: a structured review of the literature.Critical Care 21.1 (2017): 324.

Rose, John C., et al. "Comparison of effects of angiotensin and norepinephrine on pulmonary circulation, systemic arteries and veins, and systemic vascular capacity in the dog." Circulation 25.1 (1962): 247-252.

Kurtz, Armin. "Control of renin synthesis and secretion." American journal of hypertension 25.8 (2012): 839-847.