Question 12

Describe autoregulation within peripheral circulations

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College Answer

Most candidates failed to fully comprehend the question. Candidates displayed some difficulty 
in differentiating regulation at a local level (which is what the question asked for) from that of 
central regulation (e.g. sympathetic nervous system activity, cardiac output, etc.), which was 
not what the question asked for. Other omissions were a failure to define and explain 
autoregulation. Most candidates mentioned the myogenic and the metabolic theories, but 
failed to provide sufficient details as to their mechanisms. It was expected candidates would 
provide some detail as to locally acting factors. Adenosine and nitric oxide were mentioned 
on occasions but others such as endothelin and prostacyclin were often omitted. 

Discussion

  • Definition of regional blood flow autoregulation:
    • "The tendency for blood flow to remain constant despite changes in arterial perfusion pressure" - Johnson, 1986
  • Mechanisms which mediate regional autoregulation:
    • Myogenic mechanisms
      • This is an intrinsic property of all vascular smooth muscle
      • Vessel wall stretch produces smooth muscle cell depolarisation
      • Depolarisation opens voltage-gated calcium channels
      • Calcium influx produces vasoconstriction by myosin light chain phosphorylation
    • Metabolic mechanisms
      • Blood flow increases in response to increased tissue demand, eg. in exercising skeletal muscle
      • This is attributed to the release of metabolic byproducts with vasodilating properties
      • Potential mediators include potassium, hydrogen peroxide, lactate, hydrogen ions (pH), adenosine, ATP and carbon dioxide
    • Flow or shear-associated regulation 
      • This is the phenomenon of proximal vasodilation in response to distal vasodilation.
      • This shear stress promotes the release of various vasodilatory mediators from the affected endothelium and produces vasodilation of the larger proximal arteriole.
    • Conducted vasomotor responses
      • Regional control of one region by the vasomotor events of another neighbouring region.
      • Mediated by conduction of cell-to-cell signals from a small arteriole upstream to a larger arteriole
    • Organ-specific regulatory mechanisms:​​​​​​​
      • Hepatic arterial buffer response: 
        • hepatic arterial flow increases if portal venous flow decreases, and vice versa. 
      • Renal 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 arterolar vasoconstriction
      • Maternoplacental blood flow
        • Blood flow is gradually upregulated over the course of pregnancy by the actions of the trophoblast asit invades the spiral arteries of the uterus

References

Clifford, Philip S. "Local control of blood flow." Advances in physiology education 35.1 (2011): 5-15.

Green, Harold D., and John H. Kepchar. "Control of peripheral resistance in major systemic vascular beds." Physiological reviews 39.3 (1959): 617-686.

Bayliss, William Maddock. "On the local reactions of the arterial wall to changes of internal pressure." The Journal of physiology 28.3 (1902): 220.

Johnson, Paul C. "Autoregulation of blood flow." Circulation research 59.5 (1986): 483-495.

JOHNSON, PC. "Symposium on autoregulation of blood flow." Circ Res 15.1 (1964): 1-291.

Hill, Michael A., and Michael J. Davis. "Coupling a change in intraluminal pressure to vascular smooth muscle depolarization: still stretching for an explanation." American Journal of Physiology-Heart and Circulatory Physiology 292.6 (2007): H2570-H2572.

Schubert, Rudolf, and Michael J. Mulvany. "The myogenic response: established facts and attractive hypotheses." Clinical science 96.4 (1999): 313-326.

Meininger, G. A., and M. J. Davis. "Cellular mechanisms involved in the vascular myogenic response." American Journal of Physiology-Heart and Circulatory Physiology 263.3 (1992): H647-H659.

Koller, Akos, and Zsolt Bagi. "On the role of mechanosensitive mechanisms eliciting reactive hyperemia." American Journal of Physiology-Heart and Circulatory Physiology 283.6 (2002): H2250-H2259.

Segal, Steven S., and Brian R. Duling. "Propagation of vasodilation in resistance vessels of the hamster: development and review of a working hypothesis." Circulation Research 61.5_supplement (1987): II-20.