Circulation

Microcirculation: The microcirculation is comprised of small blood vessels like the arterioles, capillaries, venules and lymphatics. Arterioles determine the TPR and regulate the amount of blood flow to the capillaries by opening or closing the precapillary sphincter. Arterioles have sympathetic alpha 1 and alpha 2 receptors. Capillaries are the site of diffusion and osmosis. Lipid soluble substances and gases can easily cross the capillary wall by diffusion. Capillaries may have aqueous clefts which facilitate the transfer of water and water soluble substances. Exchange of substances by osmosis is dictated by Starling’s forces which are the hydrostatic and oncotic pressures exerted by the capillary and interstitium.

Fluid movement across capillary wall is given by the Starling equation as follows -

Jv = K [(Pc - Pi) - σ (π c - π i)]

Starling’s equation states that fluid flux (J v ) is the difference between hydrostatic (P c-P i ) and oncotic (π c-π i ) pressure. P c is the capillary hydrostatic pressure, P i is the interstitial hydrostatic pressure, π c is the capillary oncotic pressure, and π i is the interstitial oncotic pressure. K is the filtration coefficient representing the conductance or relative ease of fluids to cross the membrane, and σ is the reflection coefficient, which represents the permeability of the membrane or pore size which determines relative ease with which proteins can cross the membrane. Reflection coefficient value is inversely proportional to the protein permeability. The value is low in hepatic sinusoids and high in brain.

Forces favoring filtration from the capillary are the capillary hydrostatic pressure and interstitial oncotic pressure while forces favoring absorption into the capillary are capillary oncotic pressure and interstitial hydrostatic pressure. Plasma proteins, mainly albumin, determines the capillary oncotic pressure while the arterial and venous pressures determine the hydrostatic pressure. π c will decrease in protein malnutrition, nephrotic syndrome and liver failure. Pc will increase in heart failure. Conductance will increase due to damage of blood vessel wall in burns, inflammation and trauma.

Regulation of local circulation: Local circulation can be altered in response to local tissue needs and metabolism. It is seen in autoregulation, active hyperemia and reactive hyperemia.

1. Myogenic hypothesis: When arterial pressure increases, it stretches the arterioles which then constrict, which helps to maintain a constant flow in spite of increased pressure. The opposite effect i.e. arteriolar dilation is seen when the pressure decreases. It follows Laplace’s law which states that T = P X r, where T is the tension on the vessel wall, P is the pressure and r is the radius of the vessel. So when P increases r can be reduced to keep the T constant.

2. Metabolic hypothesis: Tissue metabolism leads to an increase in the local concentration of vasoactive metabolites like H+, K+, lactate, adenosine and CO2. These metabolites cause arteriolar vasodilation and increase in local blood flow. When pressure rises, local vasodilator metabolites are washed off leading to relative vasoconstriction.

3. Neurohormonal regulation of local blood flow: Peripheral blood vessels are innervated by the sympathetic nervous system. The vasculature of the skin and skeletal muscle have more sympathetic innervation compared to the internal organs. Stimulation of alpha 1 receptors on the cutaneous blood vessels causes vasoconstriction which also helps to retain body heat. Skeletal muscle vasculature shows contrasting effects of vasoconstriction following alpha 1 stimulation and vasodilation on beta 2 stimulation. Histamine released by mast cells causes vasodilation of arterioles but constriction of the venules leading to fluid accumulation in the interstitium and edema. Bradykinin has similar effects. In addition, bradykinin also stimulates the production of nitric oxide and prostacyclins. Serotonin and thromboxane A2 cause local vasoconstriction. Prostacyclins or prostaglandin I 2 (stimulates Gs) and prostaglandin E 2 (stimulates Gs) are vasodilators while prostaglandin F2 alpha (stimulates Gq) is a vasoconstrictor. Leukotriene LTC4 is a potent vasoconstrictor.

Regional circulations: The regional circulations show characteristic differences in regulation dependent on organ function and metabolic need.

1. Coronary circulation: It is controlled locally mainly by adenosine and hypoxia. Both lead to vasodilation. The heart has the highest oxygen consumption per unit weight for any organ in the body and a very high extraction rate for oxygen. Hypoxia decreases ATP production which leads to the opening of K -ATP channels causing hyperpolarization of vascular smooth muscle, reduced calcium entry into the vascular smooth muscle and vasodilation. Opening of K - ATP channels in endothelial cells leads to increased formation of nitric oxide and vasodilation.

   The subendocardial tissue is the last to receive oxygenation. Increased myocardial contractility increases oxygen demand and leads to active hyperemia. Mechanical compression of intracardiac vessels occurs during systole which temporarily obstructs the blood supply, hence it is followed by reactive hyperemia. In ischemic heart disease, even small reductions in perfusion pressure can negatively affect circulation across a stenosed vessel.

2. Pulmonary circulation: It is unique in that it undergoes vasoconstriction in response to hypoxia. It is needed to shunt blood away from poorly ventilated to well ventilated areas. The pulmonary circulation is almost fully dilated even under resting conditions. Nitric oxide and prostacyclin are important local vasodilators and they help to maintain a low pulmonary vascular tone

3. Cerebral circulation: The most important regulator of local cerebral circulation is CO2 (H+). Increase in cerebral Paco2 causes a rise in H+ and acidosis leading to vasodilation. The unique feature of cerebral circulation is that large extracranial and intracranial arteries are major contributors to cerebral vascular resistance.

4. Renal circulation: Renal autoregulation is exhibited even in denervated kidneys. Myogenic mechanisms and tubuloglomerular feedback are vital in maintaining renal circulation.

5. Skeletal muscle: Circulation is affected mostly by local metabolites during exercise and by sympathetic system under resting conditions. At rest, activation of alpha 1 receptors on vascular smooth muscle by norepinephrine causes vasoconstriction. Release of epinephrine from the adrenal medulla causes vasodilation by activating the beta 2 receptors on vascular smooth muscle. During exercise, accumulation of lactate, adenosine and K+ causes vasodilation

6. Skin: Cutaneous circulation is affected mainly by sympathetic innervation of the blood vessels. When body temperature rises, it leads to inhibition of sympathetics resulting in vasodilation of cutaneous vessels and dissipation of body heat. The opposite response is seen in cold weather or hypothermia.