Viva G4(ii)d

This viva tests Section G4(ii) of the 2017 CICM Primary Syllabus, which expects the exam candidate to "describe the distribution of blood volume and flow in the various regional circulations and explain the factors that influence them, including autoregulation. These include, but not limited to, the cerebral and spinal cord, hepatic and splanchnic, coronary, renal and uteroplacental circulations."

Specifically, this viva is all about coronary blood flow.

Describe the blood supply of the heart.
  • Right coronary artery: lies in the groove between the right ventricle and the right atrium; runs anteriorly, and then posteriorly to encircle the heart
  • Left main: short; divides into two branches:
    • Left anterior descending (descends anteriorly, as the name suggests)
    • Left circumflex (descends posteriorly in the atrioventricular groove)
  • Anastomosis between the arteries exists at the arteriolar level

coronary arteries schematic representation

How much blood flow does the coronary circulation receive?
  • 5% of cardiac output, or 50-120ml/100g of myocardial mass
  • The coronary flow is biphasic: there is a small peak of flow during systole, then an interruption, and then another longer taller peak of greater flow during diastole. 

events in coronary blood flow during the cardiac cycle

  • 75% of the left main flow and 50% of RCA flow occurs in diastole
  • In systole, LV blood flow is reduced due to the high chamber pressure during contraction
  • For the RV, the systolic chamber pressure is lower, and blood flow is less affected 
  • Thus, diastolic time is more important for LV perfusion, and it can be compromised by tachycardia
How do the blood supplies of the left and right ventricles differ?
  • Left ventricular coronary flow is:
    • Sharply decreases during isometric contraction (and can in fact be negative)
    • Sharply increases during the early part of systole
    • Reaches its systolic maximum during the summit of aortic pressure
    • Decreases significantly with a decrease in aortic pressure (and, again, can become negative)
    • Increases sharply during isovolumetric relaxation
    • Is maximal at mid-diastole
    • Decreases gradually in late diastole, following the diastolic pressure gradient.
  • Because the LV produces a higher internal pressure during systole, systolic coronary resistance is increased, and systolic coronary blood flow is lower. As a result, the left ventricle is better perfused in diastole.
  • Right ventricular coronary flow is similar but is higher during ventricular systole because the right ventricular systolic chamber pressure is usually lower.
    • As a result, the right ventricle is equally well perfused in systole and diastole.
    • This means the right ventricle does not depend on diastolic filling time and is therefore less affected by tachycardia.
What determines coronary blood flow?
  • Myocardial oxygen extraction ratio is already very high (60-70%).
  • Thus, the myocardium cannot increase its oxygen extraction efficiency to meet increased metabolic demand
  • Thus, coronary arterial blood flow increases to match myocardial oxygen demand, and the oxygen extraction ratio remains stable.
  • This autoregulation is achieved by adjusting the myocardial arteriolar resistance.
  • Factors that influence this arteriolar resistance are "metabolic, physical and neuro-humoral factors"
What mechanisms are implicated in coronary autoregulation?
  • Metabolic byproducts and substrates:
    • Adenosine
    • Oxygen and carbon dioxide 
    • Potassium
    • Hydrogen peroxide
    • pH and lactate
    • Nitric oxide 
    • ATP-sensitive potassium channels also open in response to decreased ATP, resulting in smooth muscle membrane hyperpolarisation and thus relaxation
  • Myogenic mechanisms (activated by stretch, due to increased flow)
  • Autonomic nervous system
    • α1-adrenergic receptor activation stimulates vasoconstriction
    • β-adrenergic receptor activation produces vasodilation
    • Muscarinic receptor stimulation produces coronary vasodilation
What if the sympathetic nervous system is activated?  How does coronary blood flow react to a "fight or flight" response?
  • The sympathetic nervous system activation would result in noradrenaline release and vasoconstriction.
  • However,  "autoregulatory escape" occurs, with metabolic factors taking over and instead producing vasodilation
  • Plus, the coronary circulation is also well-supplied with β-adrenoreceptors which promote vasodilation
  • Thus, coronary blood flow increases to match the demands imposed by the exercise of the "fight or flight" response, ignoring the excess of vasoconstrictor catecholamines
Which other pharmacological agents influence coronary blood flow?
  • Vasodilators:
    • Dipyridamole
    • Adenosine
    • Nitrates, eg. glyceryl trinitrate
    • Theophylline
  • Vasoconstrictors:
    • Vasopressin and terlipressin
    • Noradrenaline and phenylephrine
    • Indirectly, COX inhibitors

References

Eipel, Christian, Kerstin Abshagen, and Brigitte Vollmar. "Regulation of hepatic blood flow: the hepatic arterial buffer response revisited." World journal of gastroenterology: WJG 16.48 (2010): 6046.

Abshagen, K., et al. "Anatomy and physiology of the hepatic circulation." PanVascular Medicine (2015): 3607-3629.

Greenway, C. V., and R. D. Stark. "Hepatic vascular bed." Physiological reviews 51.1 (1971): 23-65.

Dancygier, Henryk. "Hepatic Circulation." Clinical Hepatology. Springer, Berlin, Heidelberg, 2010. 55-59.

BALFOUR, DONALD C., et al. "Hepatic vein pressure studies for evaluation of intrahepatic portal hypertension." AMA archives of surgery 68.4 (1954): 442-447.

Lautt, W. WAYNE, et al. "Localization of intrahepatic portal vascular resistance." American Journal of Physiology-Gastrointestinal and Liver Physiology 251.3 (1986): G375-G381.

Chamberlain, Ronald S. "Essential functional hepatic and biliary anatomy for the surgeon." Hesham A. Hepatic surgery. Newark, NJ: InTech (2013): 41-60.

Okudaira, Masahiko. "Anatomy of the portal vein system and hepatic vasculature." Portal Hypertension. Springer, Tokyo, 1991. 3-12.\

Brown, H. S., et al. "Measurement of normal portal venous blood flow by Doppler ultrasound." Gut 30.4 (1989): 503-509.

HARDIN, ROBERT A., HARRIS B. SHUMACKER, and CHIEN SHENG SU. "Studies on portal venous oxygen saturation." Archives of Surgery 87.5 (1963): 831-835.

Lutz, J., H. Henrich, and E. Bauereisen. "Oxygen supply and uptake in the liver and the intestine." Pflügers Archiv 360.1 (1975): 7-15.

Tygstrup, Niels, et al. "Determination of the hepatic arterial blood flow and oxygen supply in man by clamping the hepatic artery during surgery.The Journal of clinical investigation 41.3 (1962): 447-454.

Finnerty, Eoin, et al. "Noninvasive quantification of oxygen saturation in the portal and hepatic veins in healthy mice and those with colorectal liver metastases using QSM MRI." Magnetic resonance in medicine 81.4 (2019): 2666-2675.

Wake, Kenjiro, and Tetsuji Sato. "“The Sinusoid” in the Liver: Lessons Learned from the Original Definition by C harles S edgwick M inot (1900)." The Anatomical Record 298.12 (2015): 2071-2080.

Henriksen, Jens H., and Niels A. Lassen. "Pressure profile in liver sinusoids: A model of localization of sinusoidal resistance in the normal and cirrhotic liver." Liver 8.2 (1988): 88-94.

Guntheroth, Warren G., and Gay L. Mullins. "Liver and spleen as venous reservoirs." American Journal of Physiology-Legacy Content 204.1 (1963): 35-41.

Baik, Soon Koo, et al. "Acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis: a randomized comparison." American Journal of Gastroenterology 100.3 (2005): 631-635.

Richardson, Peter DI, and Peter G. Withrington. "Liver blood flow: II. Effects of drugs and hormones on liver blood flow." Gastroenterology 81.2 (1981): 356-375.

Blei, Andres T. "Vasodilator therapy of portal hypertension: Focus on the liver." Hepatology 9.6 (1989): 896-899.

Dauzat, M., et al. "Meal induced changes in hepatic and splanchnic circulation: a noninvasive Doppler study in normal humans." European journal of applied physiology and occupational physiology 68.5 (1994): 373-380.

Lautt, W. Wayne, Dallas J. Legare, and Waleed R. Ezzat. "Quantitation of the hepatic arterial buffer response to graded changes in portal blood flow." Gastroenterology 98.4 (1990): 1024-1028.

Jakab, F., et al. "The interaction between hepatic arterial and portal venous blood flows; simultaneous measurement by transit time ultrasonic volume flowmetry." Hepato-gastroenterology 42.1 (1995): 18.

Lautt, W. W., D. J. Legare, and M. S. d'Almeida. "Adenosine as putative regulator of hepatic arterial flow (the buffer response)." American Journal of Physiology-Heart and Circulatory Physiology 248.3 (1985): H331-H338.