Question 23

College Answer

Candidates were expected to present the cellular mechanisms underlying the control of 
skeletal muscle blood flow. Many candidates correctly identified a role for sympathetic 
nervous system, metabolic (e.g. vasodilator metabolites such as CO2, H+, K+, lactate and 
adenosine), vasoactive substances released by endothelium (nitric oxide, prostacyclin, 
endothelin 1, etc.) and autoregulatory control but failed to present any details of direction 
and magnitude of control. Better answers also mentioned humeral (e.g. catecholamines, 
vasopressin, ANP, angiotensin II, histamine, serotonin, etc.) or myogenic control (i.e. when 
the pressure within a smooth muscle blood vessel is suddenly increased, the vascular 
smooth muscle is stretched. 

Discussion

Though normally nothing escapes the hollow pitiless gaze of the CICM copy editors, one must point out that "humeral" factors would be those directly related to the humerus. In any case, the substances mentioned there (vasopressin, serotonin, histamine) are generic vasoactive mediators, insofar as they do nothing unique in the circulation of skeletal muscle (i.e. nothing that they don't do in every other regional circulatory system).

• Normal skeletal muscle blood flow
  • At rest, 1-4ml/min/100g of muscle tissue
  • With vigorous exercise, up to 400ml/min/100g
  • In shock states, down to 0.1-0.4ml/min/100g
• Purpose of regulatory control of skeletal muscle perfusion
  • Autoregulation: to maintain feedback control of blood flow
  • Metabolic regulation: to ensure supply meets demand
  • Systemic regulation: to redistribute blood flow away from muscle to ensure the perfusion of vital organs duing shock
• Intrinsic vascular mechanisms
  • Myogenic control, an intrinsic property of all vascular smooth muscle
  • Vessel wall stretch produces a calcium-mediated reflex vasoconstriction
• Vasoactive substrates and products of muscle metabolism
  • Muscle hypoxia produces vasodilation
  • Metabolic byproducts (CO₂, lactate, hydrogen peroxide and potassium ions) act as vasodilators
  • Regional decreases in pH produce vasodilation independently of CO₂ and lactate
• Vasoactive mediators released by the endothelium can alter skeletal muscle blood flow, though they do not seem to be essential for exercise-induced hyperemia:
  • Nitric oxide (NO)
  • Adenosite triphosphate (ATP)
  • Adenosine
  • Prostaglandins
  • Endothelium-derived hyperpolarization factors (EDHFs)
• Regulation by the autonomic nervous system
  • α-1 receptor activation leads to skeletal muscle vasoconstriction
    • Sympathetic innervation vasconstricts skeletal muscle arterioles to maintain a high resting vessel tone for inactive muscle
    • In haemorrhagic shock, α-1 receptor activation helps redistribute blood flow away from muscle
  • β-2 receptor activation leads to skeletal muscle vasodilation
    • Systemic adrenaline release increases muscle blood flow for "fight or flight" responses, in addition to increasing cardiac output, increasing the capacity for muscle activity

Korthuis, R. J. "Regulation of vascular tone in skeletal muscle." Skeletal muscle circulation (2011): 7-34.

Saltin, B., et al. "Skeletal muscle blood flow in humans and its regulation during exercise." Acta physiologica Scandinavica 162.3 (1998): 421-436.

Jones, Richard D., and Robert M. Berne. "Intrinsic regulation of skeletal muscle blood flow." Circulation research 14.2 (1964): 126-138.

Mortensen, Stefan P., and Bengt Saltin. "Regulation of the skeletal muscle blood flow in humans." Experimental physiology 99.12 (2014): 1552-1558.

Lejemtel, Thierry H., and Stuart D. Katz. "Skeletal muscle blood flow." Cardiac Output and Regional Flow in Health and Disease. Springer, Dordrecht, 1993. 469-478.