14A12: Exam Report

Describe autoregulation within peripheral circulations.

8% of candidates passed this question.

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.

G4ii / 14A12: Describe autoregulation within peripheral circulations

Autoregulation = the intrinsic ability of an organ to maintain constant blood flow despite changes in perfusion pressure

  • Autoregulation occurs in absence of neural/humoral influences → ∴it is an intrinsic feature of an organ
  •   \( \textbf{BLOOD FLOW = } \frac{\text{PA – PV}}{\text{RESISTANCE}} \textbf{ OR } \frac{\text{MAP}}{\text{Organ Vascular R}} \)
  • When perfusion pressure (PA – PV) ↓ → ↓blood flow
  • Activates myogenic & metabolic mechanisms which cause VD → ↓R →  maintain BF despite ↓perfusion P
  • Maintaining BF over wide range of perfusion pressures is important → e. hypoT 2° blood loss →  doesn’t compromise BF to heart/brain despite ↓strong sympathetic drive & BaroR responses to hypoT
  • All vascular beds exposed to the same MAP

Distribution of CO determined by vessel diameter which has:

  1. EXTRINSIC CONTROL: symp. NA, adrenal medulla, kidneys → MAP maintenance
  2. INTRINSIC CONTROL: local myogenic, local metabolic, local vasoactive chemicals → regulate flow to individual organs

Tissue Factors

  • Metabolic theory
  • ↑/↓vasoactive substances in relation to tissue metabolism ∴ensure O2/substrate is supplied & products of metabolism removed
  • Produced by tissues surrounding blood vessels
  • Cause contraction/relaxation of smooth m.

Adenosine: potent VD

pO42: VD


H+: VD

K+: hyperpolarises smooth m. →  VD

O2: ↓PO2 →  VD

Osmolarity: ↑osmolarity →  VD

Histamine: from MC →  potent VD


AA metabolites: VD

\( \textbf{VD: } \begin{cases} \text{Thromboxane} \\ \text{Leukotrienes} \end{cases} \)

Endothelial Factors

  • Produced by endothelium
  • Produced in response to hormones, shearing forces, hypoxia, drugs


  • Produced by NO synthetase activity on L-arginine
  • Diffuses from endothelial cell to smooth m.
  • Activates guanylyl cyclase → ↑cAMP →  ↓Ca2+ →  ↓calmodulin activation →  smooth m. relaxation


  • Formed by COX-1 activity on AA
  • Activates AC → ↑cAMP →  ↓MLCK activity →  VD & ↓platelet aggregation


  • Synthetised by Endothelin Converting Enzyme
  • Binds ETA receptors on smooth m. cells
  • ETA receptors are coupled to Gq proteins → potent VC
  • Synthesis stimulated by AII, vasopressin, thrombins, cytokines, shear forces, ROS
  • Synthesis inhibited by NO, prostacyclin, ANP

Extra Vascular Compression

  • External mechanical compression → alters vessel radius →  ∆ R
  • ↓Transmural P (Inside P – Outside P)
  • Vessels can completely collapse e. LCA in systole

Myogenic Mechanism

  • The basis of Pressure Autoregulation
    • ↑intravascular P
    • Distends vessel
    • ↑transmural P
    • Smooth m. cell depolarises when stretched
    • Ca2+ enters cell
    • Phosphorylation of MLCK
    • Smooth m. contraction

NB →  Abolished by SNP