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:
- EXTRINSIC CONTROL: symp. NA, adrenal medulla, kidneys → MAP maintenance
- INTRINSIC CONTROL: local myogenic, local metabolic, local vasoactive chemicals → regulate flow to individual organs
- TISSUE FACTORS
- ENDOTHELIAL FACTORS
- MYOGENIC MECHANISM
- EXTRAVASCULAR COMPRESSION
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
CO2: VD
H+: VD
K+: hyperpolarises smooth m. → VD
O2: ↓PO2 → VD
Osmolarity: ↑osmolarity → VD
Histamine: from MC → potent VD
BK: 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
NO
- 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
Prostacyclin
- Formed by COX-1 activity on AA
- Activates AC → ↑cAMP → ↓MLCK activity → VD & ↓platelet aggregation
Endothelin-1
- 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
- MYOGENIC MECHANISM
- ↑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