Local & Regional Control of Blood Flow

Principles of local control

Autoregulation. Many organs hold their blood flow nearly constant as perfusion pressure varies over a physiologic range. They do this by adjusting arteriolar radius. Resistance varies inversely with the fourth power of the radius, so small changes in diameter produce large changes in flow. Autoregulation is most robust in the brain, heart and kidney and weakest in the skin. Two mechanisms work together.

Myogenic mechanism. A rise in pressure stretches arteriolar smooth muscle and opens stretch-activated cation channels. The cell depolarizes, voltage-gated L-type Ca2+ channels let calcium in, and the muscle contracts. Resistance rises and flow returns toward baseline. A fall in pressure relaxes the vessel. The response is intrinsic to the muscle, needs no nerves or hormones, and is most important in renal afferent arterioles and cerebral vessels.

Metabolic mechanism. Active tissue releases adenosine, CO2, H+ (from lactic acid), K+ and heat. It also lowers local PO2 and raises interstitial osmolarity. All of these relax arterioles, so flow follows metabolic demand. Metabolic control dominates in the heart, exercising skeletal muscle and the brain.

Active vs reactive hyperemia. In active (functional) hyperemia, flow rises in proportion to metabolic activity, as in contracting muscle, the gut after a meal or active brain regions. Reactive hyperemia is the brief surge above baseline after an arterial occlusion is released. Its size and duration grow with the length of the occlusion, as accumulated metabolites and myogenic relaxation repay the O2 debt.

Endothelial and humoral mediators

Endothelial signals. The endothelium sets local tone. Damaged endothelium, as in atherosclerosis, tips the balance toward constriction. In diseased coronary arteries acetylcholine can even cause paradoxical constriction, because NO no longer offsets its direct effect on smooth muscle.

Nitrates plus a PDE-5 inhibitor such as sildenafil drive cGMP far higher than either drug alone and can cause profound hypotension.

Circulating hormones. Angiotensin II and ADH constrict; natriuretic peptides (cGMP), histamine and bradykinin (largely via NO) dilate.

Coronary circulation

Flow must rise with demand. At rest the myocardium already extracts about 70–80% of the O2 delivered to it, so coronary sinus blood is the most desaturated venous blood in the body. More extraction is not possible, and extra O2 demand must be met with extra flow. Coronary flow is about 5% of cardiac output. It follows metabolism through adenosine and NO and can increase several-fold. The net effect of sympathetic stimulation is dilation, because the added metabolic demand outweighs direct α1 constriction.

Diastolic perfusion. During systole the contracting LV squeezes its intramyocardial vessels, so most LV flow occurs in diastole. The thinner-walled RV is perfused throughout the cycle. Coronary perfusion pressure is approximately aortic diastolic pressure minus LV end-diastolic pressure. It falls with hypotension or aortic regurgitation (lower diastolic pressure) and with heart failure (higher LVEDP). Tachycardia shortens diastole and cuts perfusion time. The subendocardium bears the greatest compressive stress and lies at the far end of the penetrating arteries, so it becomes ischemic first.

Coronary steal. Pharmacologic stress agents dilate coronary arterioles. Adenosine and regadenoson act on A2A receptors; regadenoson is a selective A2A agonist. Dipyridamole blocks cellular reuptake of adenosine. Arterioles beyond a significant stenosis are already maximally dilated, so the drug increases flow only in normal beds. Flow is diverted away from the stenotic territory, producing ischemia or a perfusion defect on imaging. Caffeine and theophylline antagonize adenosine receptors, so caffeine is withheld before the test, and aminophylline reverses vasodilator side effects.

Brain, skeletal muscle and skin

Brain. Cerebral blood flow (about 15% of cardiac output) is autoregulated between a MAP of roughly 60 and 150 mmHg. Below that range the brain becomes ischemic. Above it, hyperperfusion causes edema, as in hypertensive encephalopathy. Chronic hypertension shifts the whole curve to the right, so abrupt BP lowering can cause cerebral hypoperfusion. The dominant chemical controller is PaCO2. CO2 crosses the blood–brain barrier and lowers perivascular pH, dilating arterioles, while hypocapnia constricts them. Brief hyperventilation to a PaCO2 of about 30–35 mmHg quickly reduces cerebral blood volume and ICP. The effect fades within hours as CSF pH readjusts, and excessive hyperventilation causes ischemia. Hypoxemia dilates cerebral vessels only when PaO2 falls below about 50 mmHg. Sympathetic nerves have little effect on cerebral flow.

Skeletal muscle. Resting muscle receives about 15% of cardiac output under sympathetic control: α1 receptors constrict and β2 receptors, stimulated by circulating epinephrine, dilate. During exercise, local metabolites (adenosine, K+, lactate and H+, CO2) override sympathetic constriction and flow rises many-fold. The muscle pump helps return blood to the heart.

Skin. Skin flow serves temperature regulation, not metabolism, and is controlled almost entirely by sympathetic α1 tone. Cold increases tone and constricts the vessels. Heat withdraws tone and opens arteriovenous anastomoses (glomus bodies) in the fingers, toes, ears and nose, which shunt warm blood to the surface to lose heat. Skin has little metabolic autoregulation, so during hemorrhage sympathetic constriction of skin and splanchnic beds redirects blood to the brain and heart.

The lung exception and organ comparison

Hypoxic pulmonary vasoconstriction. In the lung, alveolar hypoxia constricts the arterioles supplying poorly ventilated units. Blood is redirected to well-ventilated alveoli, improving ventilation–perfusion (V/Q) matching. Systemic arterioles do the opposite and dilate in hypoxia. When hypoxia is global and chronic, as in COPD or at high altitude, widespread constriction causes pulmonary hypertension, right ventricular hypertrophy and eventually cor pulmonale.

Flow versus extraction. The heart receives little flow but extracts the most O2, so it has the widest arteriovenous O2 difference. The kidney has the highest flow per gram because its flow serves filtration, not metabolism, so its arteriovenous difference is narrow. The liver takes the largest share of cardiac output through a dual supply, mostly portal.