L18 CVS Physiology 9 Special circulation

Overview

This lecture surveys the “special circulations” supplying six organ systems - heart (coronary), brain (cerebral), skin (cutaneous), gut (splanchnic), liver (hepatic) and kidney (renal) - using a consistent framework for each: its special task, its structural and functional adaptations, how its flow is regulated (myogenic, metabolic, or extrinsic/neural), and the special problems that arise when that regulation fails or the anatomy predisposes to injury.

Coronary circulation

• Two major coronary arteries arise from the base of the aorta and run over the heart surface toward the apex
  • Right coronary artery (RCA): right ventricle, part of the septum, posterior wall of the left ventricle
  • Left coronary artery: rest of the heart, via its major branch the left anterior descending (LAD), which supplies part of the septum
• Receives 4% of cardiac output, 200-250 ml/min at rest
• Flow: 70-80 ml/min/100g of tissue at rest, rising to 300-400 ml/min/100g during heavy exercise
• Venous drainage: 95% via the coronary sinus; the rest via anterior cardiac veins and thebesian veins. The thebesian vein drains directly into the left ventricle, slightly deoxygenating arterial blood (saturation ~97%)

Flow variations across the cardiac cycle

• Flow depends on systole vs diastole, driven by (1) rhythmic pulsations in aortic pressure and (2) changing intramural myocardial pressure
• Left ventricle: during systole, rising intramural pressure compresses the coronary vessels (mainly in the sub-endocardium), interrupting LV flow almost completely in early systole. LV blood flow therefore occurs mainly during diastole
• Right ventricle: intramural pressure is lower, so RCA flow continues during systole and simply tracks the fluctuations in aortic pressure

Regulation

• Three categories: myogenic, metabolic, extrinsic (neurogenic/ANS, endocrine)
• O2 extraction is already high at rest: the heart extracts ~75% of the O2 in coronary blood versus ~25% extraction from mixed venous blood elsewhere in the body (coronary sinus pCO2 58 mmHg/7.3 kPa vs mixed venous pCO2 46 mmHg/5.8 kPa) - because so little extraction reserve remains, extra demand must be met by extra flow rather than extra extraction
• Metabolic control is the dominant mechanism: O2 deficiency is the major dilator stimulus, and even a 5% fall in coronary arterial O2 content triggers vasodilation
• Diastolic arteriolar autoregulation maintains flow despite fluctuations in mean arterial blood pressure (metabolic)
• Adenosine: produced in myocardial cells from ATP breakdown during heavy exercise, hypoxia and ischaemia; diffuses to the extracellular space and acts directly on the arteriolar wall as a vasodilator
• Nitric oxide (NO): released from healthy endothelium
  • Shear stress and receptor-dependent activation stimulate endothelial eNOS (via the PI3-kinase-PKB pathway) -> eNOS converts $O_2+\text{L-arginine}\to NO+\text{L-citrulline}$ -> NO diffuses to vascular smooth muscle -> activates soluble guanylate cyclase -> $\text{cGTP}\to \text{cGMP}$ -> smooth muscle relaxation (vasodilation)
• Neurogenic factors are both vasodilatory (β-adrenergic) and vasoconstrictory (α-adrenergic): sympathetic noradrenaline acts on α2 autoreceptors (inhibitory feedback on further NE release) and on α1/α2 receptors of the vessel wall (vasoconstriction), while β receptors mediate vasodilation

Special problem: functional end-arteries

Coronary arteries are functional end-arteries with no effective anastomotic supply, unlike regions such as the hand, whose arterio-arterial anastomoses let collateral flow bypass an obstruction. When atheroma (lipid plaque in the tunica intima) bulges into the lumen, it causes:

• chronic narrowing -> angina on exercise/stress
• acute thrombosis -> myocardial infarction

Because coronary vessels lack anastomoses, a complete blockage produces a discrete zone of necrosis (infarction), a peripheral rim of partial ischaemia, and adjacent healthy normoxic tissue - unlike vessels with collateral supply, where distal flow can be maintained around an obstruction.

Cerebral circulation

• The brain is highly sensitive to changes in perfusion; it has no capacity for anaerobic metabolism and so needs a constant O2 supply
• Receives ~13% of cardiac output; cerebral blood flow (CBF) is held constant at ~50 ml/100g/min
• The internal carotid arteries supply the anterior circulation (80% of total CBF); the vertebral arteries supply the hindbrain (20% of total CBF). Under normal conditions there is little mixing of carotid and vertebral blood
• If one supplying artery is occluded, the Circle of Willis provides collateral compensation

Autoregulation

• CBF is held constant across a mean arterial pressure range of 50-150 mmHg
• Mechanism is myogenic: a rise in perfusion pressure constricts cerebral arterioles; a fall in perfusion pressure dilates them. After a step rise in pressure, vessel radius and flow spike initially, then the myogenic response returns them toward baseline; this constrictor response is abolished by a Ca2+ channel blocker, confirming it is myogenic

Local (metabolic) regulation

Local blood flow is regulated by vasodilator metabolites, so metabolic autoregulation matches O2 supply to the activity level of individual brain regions - different tasks (sensory stimulation, hand movement, talking, reading, reasoning, problem solving) activate flow increases in distinct, task-specific cortical regions rather than the whole brain uniformly.

CO2 and O2 sensitivity

• CBF is very sensitive to arterial PCO2: a rise in PaCO2 causes vasodilation and increased flow; a fall causes vasoconstriction and decreased flow, via $C{O}_2+H_{2}O\rightleftharpoons H_{2}C{O}_3\rightleftharpoons HC{O}_3^{-}+H^{+}$
• CBF is also affected by a fall in arterial PO2, but less than by PaCO2 changes
• If PaO2 falls enough, or MAP drops below the autoregulatory range, CBF falls and O2 delivery is impaired, producing syncope, faint or coma

CSF, intracranial pressure and CBF

• The brain is encased in a rigid cranium and floats in CSF, which also performs the lymphatic-drainage role the brain otherwise lacks
• The combined volumes of blood, brain and CSF inside the cranium are fixed - there is no capacity to increase total volume
• A rise in intracranial pressure (e.g. oedema, blocked CSF flow) compresses cerebral vessels and reduces CBF
• The fall in CBF is countered by: local vasodilation; the local rise in PCO2 and fall in PO2; and stimulation of the cardiovascular centres, which activates vasomotor sympathetic activity to the heart and systemic vessels, raising MAP to restore CBF (Cushing reflex)

Cutaneous circulation

• At rest the skin receives ~8% of cardiac output; during heavy exercise cutaneous flow can rise 3-4 fold - a rise driven by thermoregulation, not increased skin metabolic demand
• Capillary loops rise from the dermis toward the epidermis; in the extremities, arteriovenous anastomoses (AVAs) connect arterioles directly to veins and are controlled by sympathetic vasoconstrictor fibres
• Heat carried through the AVAs raises skin temperature, increasing heat loss by radiation, conduction-convection and evaporation

Regulation by temperature

• Cutaneous flow is affected by both ambient and core temperature
• Vasodilation and sweating are produced by increased sympathetic cholinergic (vasodilator) fibre activity to skin resistance vessels, together with decreased sympathetic vasoconstrictor drive to the AVAs in the extremities
• Forearm blood flow stays low until core temperature (raised, e.g., by leg exercise) exceeds ~37.5degC, after which flow rises sharply - a temperature threshold for cutaneous vasodilation

Response to local cooling

• Local cooling (e.g. by ice) first causes cold-induced vasoconstriction, flattening flow at a low level
• With continued severe cold, paradoxical cold vasodilatation follows, caused by paralysis of noradrenergic neurotransmission by the cold and release of vasodilators such as prostacyclin

Special problem: Raynaud’s disease

Raynaud’s disease is an excessive vasoconstrictor response to cold; severe cold triggers the paradoxical cold vasodilatation described above. Clinically, fingertips turn white (inadequate blood flow) and then blue (as tissue O2 is depleted).

Splanchnic circulation

• Supplied by three aortic branches (total aortic flow ~4000 ml/min):
  • Coeliac artery: 700 ml/min (10% of CO), splitting into stomach/spleen/pancreas (200 ml/min) and hepatic artery (500 ml/min)
  • Superior mesenteric artery: 700 ml/min (10% of CO), to intestine/pancreas
  • Inferior mesenteric artery: 400 ml/min (5% of CO), to intestine
• Splanchnic bed overall receives 25% of cardiac output and accounts for 25% of O2 consumption
• Venous return from the stomach/spleen/pancreas and intestine/pancreas combines into the portal vein (1300 ml/min) entering the liver
• Over 65% of GI blood flow goes to the mucosa, providing energy for gastric secretion and for absorption of digested food

Regulation

• Autoregulation occurs in the stomach, small intestine and colon; it is more prominent in the fed than the fasting state, and more prominent in the (more metabolically active) mucosa
• The GI vasculature is heavily innervated by the sympathetic nervous system: SNS activation causes α-adrenoceptor-mediated vasoconstriction, diverting 200-300 ml of blood from the GI tract to vital organs when MAP falls
• During haemorrhage, GI blood flow can fall to 25% of resting flow due to SNS activation

Sensitivity to hypoperfusion

• In the intestinal villus, arterial (ascending) and venous (descending) flow run in a closely apposed countercurrent arrangement; up to 80% of O2 short-circuits from arteriole to venule via capillaries without reaching the villus tip. This is normally harmless
• In circulatory shock, cells at the villus tip become ischaemic and can die
• Severe GI hypoperfusion is poorly tolerated: mucosal disruption impairs barrier function, letting endotoxin enter the systemic circulation and cause septic shock

Hepatic circulation

• The liver receives ~25% of cardiac output to support its metabolic functions; normal total liver blood flow is ~1.5 L/min (range 1-2 L/min)
• Dual blood supply: the hepatic artery (oxygenated) and the portal vein (deoxygenated, nutrient-rich) both enter at the interlobular vein, pass through the sinusoid, then the central vein, then leave via the hepatic vein -> inferior vena cava -> right atrium
• Sinusoids have fenestrated endothelium (“sieve plates”); non-fenestrated areas overlie fat-storing cells, and the space of Disse (containing microvilli from hepatic parenchymal cells) lies beneath the endothelium

Regulation

• Portal venous blood flow is not regulated by the liver itself - it depends on the vascular resistance of the GI tract
• Hepatic arterial blood flow is under sympathetic tone (α-adrenoceptor-mediated vasoconstriction)

Hepatic Arterial Buffer Response (HABR)

Reciprocal regulation keeps total hepatic blood flow relatively constant:

• A fall in portal venous flow produces a compensatory rise in hepatic arterial flow
• A rise in portal venous flow produces a compensatory fall in hepatic arterial flow

Renal circulation

• Kidneys receive 20-25% of cardiac output at rest, ~400 ml/100g/min (compare brain 50, heart 80 ml/100g/min)
• This high flow serves function rather than metabolism - regulation of the volume and composition of body fluids via glomerular filtration and tubular reabsorption/secretion

Vascular anatomy

• Renal artery branch -> afferent arteriole -> glomerular capillaries within the glomerulus (site of filtration) -> reunite to form the efferent arteriole
• The efferent arteriole breaks up into a second capillary bed, the peritubular capillaries, which supply the rest of the nephron (site of reabsorption) -> reunite to form the renal venules

Pressure profile

• Arterial pressure (~94 mmHg) falls only slightly through the afferent arterioles (~90-93 mmHg)
• Glomerular capillary hydrostatic pressure is high and plateaus at ~55-60 mmHg - the driving force for glomerular filtration
• Pressure then drops steeply through the efferent arterioles to ~10 mmHg, and gradually further to ~3-5 mmHg through the peritubular capillaries and veins

Autoregulation of RBF and GFR

• Both renal blood flow (RBF) and glomerular filtration rate (GFR) plateau across MAP ~80-180 mmHg, rising steeply below and above this range
• Autoregulation is mostly intrinsic, via two mechanisms:
  1. Myogenic: increased pressure induces afferent arteriolar vasoconstriction; reduced pressure induces afferent arteriolar vasodilation
  2. Tubuloglomerular feedback (TGF)

Juxtaglomerular apparatus (JGA) and tubuloglomerular feedback

• The juxtaglomerular apparatus comprises the afferent arteriole (containing granular, renin-secreting cells) and the macula densa (distal tubule cells at the point where the tubule passes close to the afferent arteriole). It is positioned to sense both renal arterial pressure (via the afferent arteriole) and urine composition (via the macula densa), and it also receives direct sympathetic input onto the granular cells
• TGF loop: (1) increased GFR -> (2) increased NaCl delivery to the loop of Henle -> (3) signal generated by the macula densa -> (4) increased afferent arteriolar resistance -> (5) decreased GFR (negative feedback)

Extrinsic control: SNS/RAA

• Afferent and efferent arterioles are innervated by sympathetic neurons
• Sympathetic stimulation releases noradrenaline, acting on α-adrenoceptors, causing vasoconstriction, reduced RBF and reduced GFR
• Circulating adrenaline has the same action on RBF and GFR
• Sympathetic activation also drives renin release and angiotensin II production (renin-angiotensin-aldosterone system)

Framework for special circulations

The lecture closes by naming the framework used throughout: for each organ, consider its special tasks; its special structural and functional adaptations; its regulation; and its special problems.

Self-test

1. Describe how the right and left coronary arteries differ in the regions of the heart they supply.
2. Explain why left ventricular blood flow occurs mainly during diastole, whereas right coronary flow can occur during systole.
3. Describe the pathway by which nitric oxide is generated in coronary endothelium and produces vasodilation of the adjacent smooth muscle.
4. A patient develops a complete coronary artery blockage with no collateral supply. Explain, in terms of end-artery anatomy, why this produces a discrete zone of infarction rather than diffuse ischaemia.
5. What proportion of cardiac output does the brain normally receive, and over what mean arterial pressure range is cerebral blood flow autoregulated?
6. Describe the myogenic mechanism of cerebral autoregulation, including how the response was shown to be myogenic.
7. Explain how a rise in arterial PCO2 increases cerebral blood flow, including the relevant chemical equilibrium.
8. Describe the Cushing reflex: what triggers it, and by what pathway does it restore cerebral blood flow?
9. Explain why cutaneous blood flow can rise 3-4 fold during heavy exercise despite no rise in the skin’s own metabolic demand.
10. Distinguish cold-induced vasoconstriction from paradoxical cold vasodilatation, including the mechanism of the latter.
11. Describe the clinical presentation of Raynaud’s disease and the vascular mechanism producing the colour changes seen.
12. List the three major arterial branches of the splanchnic circulation and the percentage of cardiac output each carries.
13. Explain the countercurrent arrangement of blood flow in the intestinal villus, and why it makes the villus tip vulnerable in circulatory shock.
14. Describe the dual blood supply to the liver and trace the path of blood from the hepatic artery and portal vein to the right atrium.
15. Describe the Hepatic Arterial Buffer Response.
16. Trace the path of blood through the renal microvasculature from the renal artery to the renal vein, noting where filtration and where reabsorption occur.
17. Explain why glomerular capillary pressure remains high while pressure falls steeply across the efferent arteriole.
18. Describe the steps of the tubuloglomerular feedback loop.
19. Distinguish the two mechanisms of intrinsic renal autoregulation.
20. Predict the effect of sympathetic activation on renal blood flow and GFR, and name the additional hormonal system it triggers.
21. Compare the dominant regulatory mechanism (myogenic, metabolic, or neural) controlling resting blood flow in the coronary, cerebral and renal circulations.

Answers

Reveal answers

1. The right coronary artery supplies the right ventricle, part of the septum and the posterior wall of the left ventricle; the left coronary artery supplies the rest of the heart, its major branch (the LAD) supplying part of the septum.
2. In the left ventricle, systolic contraction raises intramural myocardial pressure enough to compress coronary vessels (mainly sub-endocardial), interrupting flow almost completely, so LV flow occurs mainly in diastole. Right ventricular intramural pressure is lower, so RCA flow is not interrupted in systole and simply follows aortic pressure.
3. Shear stress and receptor-dependent activation stimulate eNOS in endothelial cells (via the PI3-kinase-PKB pathway); eNOS converts O2 + L-arginine to NO + L-citrulline; NO diffuses to vascular smooth muscle and activates soluble guanylate cyclase, converting cGTP to cGMP, causing smooth muscle relaxation (vasodilation).
4. Coronary arteries are functional end-arteries with no effective anastomotic connections, so when the vessel is blocked, no alternative route can supply the downstream tissue - producing a discrete zone of necrosis, a peripheral rim of partial ischaemia, and adjacent normoxic tissue, rather than the collateral-preserved flow seen in anastomosing vascular beds.
5. The brain receives ~13% of cardiac output; CBF is autoregulated (held constant, ~50 ml/100g/min) across a mean arterial pressure range of 50-150 mmHg.
6. A rise in perfusion pressure constricts cerebral arterioles and a fall dilates them, keeping flow constant; this constrictor response is abolished by a Ca2+ channel blocker (leaving a sustained rise in vessel radius instead), confirming the mechanism is myogenic (dependent on Ca2+ entry into vascular smooth muscle).
7. A rise in PaCO2 increases H+ (via CO2 + H2O <-> H2CO3 <-> HCO3- + H+), which dilates cerebral vessels and increases CBF; a fall in PaCO2 has the opposite effect.
8. Raised intracranial pressure compresses cerebral vessels and reduces CBF; the fall in CBF (and the accompanying local rise in PCO2/fall in PO2) stimulates the cardiovascular centres, activating sympathetic vasomotor activity to the heart and systemic vessels, raising MAP and restoring CBF.
9. The rise is driven by thermoregulatory demand (increased sympathetic cholinergic vasodilator activity to skin vessels and decreased sympathetic vasoconstrictor drive to arteriovenous anastomoses), not by any increase in the skin’s own metabolic requirement.
10. Cold-induced vasoconstriction is an early, sustained fall in cutaneous flow during cooling. Paradoxical cold vasodilatation follows with continued severe cold and is caused by paralysis of noradrenergic neurotransmission and release of vasodilators such as prostacyclin, producing an oscillating rise in flow despite ongoing cold exposure.
11. Raynaud’s disease is an excessive vasoconstrictor response to cold; fingertips turn white as blood flow becomes inadequate, then blue as tissue O2 is depleted. Severe cold can also trigger paradoxical cold vasodilatation via the same mechanism as normal cold-induced vasodilatation (paralysis of noradrenergic transmission, prostacyclin release).
12. Coeliac artery (700 ml/min, 10% of CO), superior mesenteric artery (700 ml/min, 10% of CO), inferior mesenteric artery (400 ml/min, 5% of CO).
13. Arterial (ascending) and venous (descending) flow in the villus run closely apposed in opposite directions, so up to 80% of O2 diffuses directly from arteriole to venule via capillaries without reaching the tip - normally harmless, but in shock this “short-circuiting” leaves the villus tip ischaemic and it can die.
14. The hepatic artery (oxygenated) and portal vein (deoxygenated, nutrient-rich) both enter the liver at the interlobular vein, pass through the sinusoid, then the central vein, then leave via the hepatic vein to the inferior vena cava and right atrium.
15. The HABR is reciprocal regulation between the two hepatic blood supplies: a fall in portal venous flow produces a compensatory rise in hepatic arterial flow, and a rise in portal venous flow produces a compensatory fall in hepatic arterial flow, keeping total hepatic flow relatively constant.
16. Renal artery branch -> afferent arteriole -> glomerular capillaries (filtration) -> efferent arteriole -> peritubular capillaries (reabsorption) -> renal venules -> renal vein.
17. Glomerular capillary pressure stays high because the afferent arteriole offers relatively little resistance upstream, maintaining a high-pressure plateau across the glomerulus; pressure then falls steeply across the efferent arteriole, which offers substantial downstream resistance, dropping pressure from ~55-60 mmHg to ~10 mmHg.
18. Increased GFR raises NaCl delivery to the loop of Henle; this generates a signal at the macula densa of the JGA; the signal increases afferent arteriolar resistance; this decreases GFR back toward normal (negative feedback).
19. Myogenic: increased pressure constricts the afferent arteriole (and vice versa), acting directly on vascular smooth muscle. Tubuloglomerular feedback: changes in NaCl delivery to the macula densa alter afferent arteriolar resistance to correct GFR.
20. Sympathetic activation (via noradrenaline and circulating adrenaline acting on α-adrenoceptors) causes vasoconstriction, reducing both RBF and GFR; it also triggers renin release and angiotensin II production (the renin-angiotensin-aldosterone system).
21. Coronary: metabolic dominates (O2 deficiency/adenosine/NO), with myogenic and neurogenic contributions. Cerebral: myogenic dominates whole-brain autoregulation, with local metabolic control matching regional flow to activity. Renal: intrinsic mechanisms dominate at rest (myogenic plus tubuloglomerular feedback), with extrinsic sympathetic/RAA control becoming important in states like haemorrhage.