Overview
This lecture covers the splanchnic circulation (blood supply to the gut and associated organs) and the hepatic circulation specifically: how blood is distributed to and through the liver, how splanchnic and hepatic flow are each regulated, why the intestinal villus is especially vulnerable to hypoperfusion, the liver’s microscopic vascular architecture, its reservoir function, and how cirrhosis produces portal hypertension.
Splanchnic circulation: anatomy and flow
- The aorta supplies 4000 mL/min in total. The coeliac artery (700 mL/min, 10% of cardiac output) supplies the stomach, spleen and pancreas; the superior mesenteric artery (700 mL/min, 10% of CO) supplies intestine and pancreas; the inferior mesenteric artery (400 mL/min, 5% of CO) supplies intestine.
- Venous drainage from these organs converges into the portal vein (1300 mL/min), which enters the liver.
- The hepatic artery, arising from the coeliac trunk, carries 200 mL/min directly into the liver; a separate 500 mL/min pathway bypasses the liver, going straight to the IVC.
- Liver output is 1800 mL/min via the hepatic veins into the IVC.
- Overall, the splanchnic bed accounts for 25% of O2 consumption and 25% of cardiac output.
- Function: nutrients absorbed from the intestinal lumen are transported to the liver for storage, transformation, or direct supply to the general circulation.
- Over 65% of GI blood flow goes to the mucosa, providing energy for forming secretions and for absorption of digested food.
Regulation of splanchnic blood flow
Autoregulation:
- occurs in the stomach, small intestine and colon
- more prominent in the fed than the fasted state
- more prominent in the mucosa, which is metabolically more active
- (as perfusion pressure falls, flow is maintained better in the fed state than the fasted state, showing stronger autoregulation when fed)
Sympathetic nervous system:
- GI blood vessels are heavily innervated by the sympathetic nervous system
- activation causes α-adrenoceptor-mediated vasoconstriction
- diverts 200-300 mL/min from the GIT to “vital organs” when MAP falls
- during haemorrhage, sympathetic activation can reduce GI blood flow to 25% of resting flow
Digestion and absorption:
- within 20 min of a meal, GI blood flow can increase significantly
- the increase is almost exclusively confined to the mucosa, up to a 6-fold rise in flow
- mechanisms: metabolic vasodilation (adenosine), dilator action of GI hormones (cholecystokinin, vasoactive intestinal peptide, gastrin, secretin), and bradykinin
Sensitivity of the splanchnic circulation to hypoperfusion
- Arterial inflow and venous outflow in the intestinal villus run in opposite directions and lie close together: a countercurrent arrangement.
- Much of the blood O2 passes directly from arterioles to adjacent venules via capillaries without being carried to the villus tip; as much as 80% of the O2 can take this short-circuit.
- Under normal conditions this is not harmful, but in circulatory shock, cells at the villus tip become ischaemic and can die, since they receive the least O2 along the countercurrent path.
- Severe hypoperfusion of the GI tract is not tolerated for long: disruption of the mucosal barrier lets endotoxin enter the systemic circulation, leading to sepsis / septic shock.
Hepatic circulation: overview
- The liver receives ~25% of cardiac output to support its metabolic functions.
- Total liver blood flow is normally 1.5 L/min (range 1-2 L/min).
- Blood enters the liver via two routes: the hepatic artery and the portal vein.
Portal venous blood flow:
- venous and partly deoxygenated
- 70-80% of total liver blood flow
- portal venous pressure is low, usually 5-10 mmHg
- the site of portal vascular resistance under physiological conditions is ill-defined
Hepatic arterial blood flow:
- well-oxygenated
- 20-30% of total liver blood flow
- pressure equivalent to mean arterial pressure
- resistance resides in the hepatic arterioles, protecting the fragile sinusoids from high pressure
Flow pathway through the liver: hepatic artery + portal vein → interlobular vein → sinusoid → central vein → hepatic vein → inferior vena cava → right atrium.
Vascular and microscopic architecture of the liver
- The liver has 4 lobes: right, left, caudate and quadrate.
- Each lobe is made of hexagonal lobules. At each vertex of the hexagon is a portal tract: a branch of the portal vein, a branch of the hepatic artery, and a bile duct. A central vein sits at the centre of the “classic” lobule.
- Three ways of dividing liver tissue on the same hexagonal pattern:
- liver lobule: bounded by portal spaces, centred on one central vein
- portal lobule: defined by the direction of bile flow, spanning three adjacent portal spaces toward the portal space at its apex
- hepatic acinus: defined by blood flow, spanning between two central veins and one portal space
The transcript notes zones I/II/III around the portal space within the hepatic acinus appear on the diagram as unlabelled dashed contour lines/roman numerals, with no accompanying explanation on the slide.
- Hepatocytes are arranged in pairs of columns radiating from the central vein. Between each pair of columns runs a sinusoid (“liver capillary”), in which portal venous blood mixes with hepatic arterial blood; this blood drains into the central vein and then the hepatic vein.
- A bile canaliculus runs between the hepatocyte columns to a bile duct; bile flows in the opposite direction to blood, i.e. away from the central vein and toward the portal tract.
- Sinusoids are lined by endothelial cells containing clusters of pores (fenestrae), forming “sieve plates”; the wall is very leaky and allows plasma proteins through. Endothelium lacking fenestrae overlies processes of fat-storing cells. The space of Disse (between endothelium and hepatocytes) contains microvilli extending from the hepatocytes.
Regulation of hepatic blood flow
- 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 of the arterioles.
Reservoir function of the liver
- The liver is a large, expandable/compressible venous organ that can store large volumes of blood in its sinusoids and hepatic veins.
- It acts as a blood reservoir in times of excess blood volume and can supply extra blood in hypovolaemia.
- Normal liver blood volume is ~500 mL, about 10% of total blood volume.
- In cardiac failure, when right atrial pressure rises, liver blood volume can rise to 1 L.
- In circulatory stress, the sympathetic nervous system vasoconstricts the hepatic veins, discharging a large volume of blood, as much as 350 mL, into the systemic circulation within 1-4 minutes.
- The liver is the single most important source of extra blood in times of need (heavy exercise, severe haemorrhage).
Liver cirrhosis and portal hypertension
- Liver injury (chronic hepatitis B or C infection, iron overload, copper overload, recurrent bile duct injury, alcohol) can result in cirrhosis.
- Cirrhosis is characterised by accumulation of extracellular matrix proteins, tissue contraction, and derangement of blood flow.
- Portal and hepatic venules lie within the fibrous septa this produces; their constriction or distortion increases vascular resistance, including portal vascular resistance.
- The resulting rise in portal pressure is termed portal hypertension.
- normal portal pressure: 5-10 mmHg
- portal hypertension: 12 mmHg or higher
Self-test
- List the three named branches of the aorta that supply the splanchnic circulation, with their approximate flow and percentage of cardiac output each.
- What proportion of GI blood flow goes to the mucosa, and what does this flow support there?
- Describe how autoregulation of splanchnic blood flow differs between the fed and fasted states, and between the mucosa and other gut layers.
- Describe the effect of sympathetic activation on splanchnic blood flow, including the approximate reduction seen in haemorrhage.
- Describe the change in GI blood flow following a meal, and list the mechanisms responsible.
- Describe the countercurrent arrangement of blood flow in the intestinal villus, and explain why the villus tip is vulnerable to ischaemia during hypoperfusion.
- Explain the sequence by which severe GI hypoperfusion can progress to septic shock.
- What percentage of cardiac output does the liver receive, and what is normal total liver blood flow?
- Distinguish portal venous blood flow from hepatic arterial blood flow in terms of oxygenation, proportion of total liver flow, and pressure.
- Describe the pathway of blood flow through the liver, from entry to the right atrium.
- Distinguish the liver lobule, portal lobule and hepatic acinus by what each is defined by and its boundaries.
- Describe the structure of a hepatic sinusoid wall and explain its functional significance.
- Describe the direction of bile flow relative to blood flow within a liver lobule.
- Explain why the regulation of portal venous flow differs from the regulation of hepatic arterial flow.
- Describe the liver’s reservoir function: the normal stored blood volume, and the volume and time course of blood release during circulatory stress.
- List the causes of cirrhosis given in the lecture, and describe the mechanism by which cirrhosis produces portal hypertension, including the pressure that defines it.
- Integrative: in haemorrhagic shock, describe two distinct mechanisms from this lecture that help preserve perfusion or blood volume, and one way in which prolonged splanchnic hypoperfusion itself becomes dangerous.
Answers
Reveal answers
- Coeliac a., 700 mL/min (10% of CO), to stomach/spleen/pancreas; superior mesenteric a., 700 mL/min (10% of CO), to intestine/pancreas; inferior mesenteric a., 400 mL/min (5% of CO), to intestine.
- Over 65%; it provides energy for forming secretions and for absorption of digested food.
- Autoregulation occurs in the stomach, small intestine and colon. It is more prominent in the fed than the fasted state, and more prominent in the mucosa than other layers, since the mucosa is metabolically more active.
- Sympathetic activation causes α-adrenoceptor-mediated vasoconstriction, diverting 200-300 mL/min from the gut to vital organs when MAP falls. During haemorrhage this can reduce GI blood flow to 25% of resting flow.
- Within 20 minutes of a meal, GI blood flow rises substantially, up to 6-fold, almost entirely confined to the mucosa. This is driven by metabolic vasodilation (adenosine), dilator GI hormones (cholecystokinin, vasoactive intestinal peptide, gastrin, secretin), and bradykinin.
- Arterial inflow and venous outflow run in opposite directions, close together, within the villus. O2 diffuses directly from arterioles to adjacent venules across this short distance, so up to 80% short-circuits and never reaches the tip; in shock the tip therefore becomes ischaemic and can die.
- Prolonged severe hypoperfusion disrupts the mucosal barrier, allowing endotoxin to enter the systemic circulation, which can cause sepsis / septic shock.
- The liver receives ~25% of cardiac output; normal total liver blood flow is 1.5 L/min (range 1-2 L/min).
- Portal venous blood flow: partly deoxygenated, 70-80% of total liver flow, low pressure (5-10 mmHg). Hepatic arterial blood flow: well-oxygenated, 20-30% of total liver flow, pressure equivalent to MAP.
- Hepatic artery + portal vein → interlobular vein → sinusoid → central vein → hepatic vein → inferior vena cava → right atrium.
- Liver lobule: bounded by portal spaces, centred on one central vein. Portal lobule: defined by the direction of bile flow, spanning three portal spaces converging on one. Hepatic acinus: defined by blood flow, spanning between two central veins and one portal space.
- It is lined by endothelial cells with clusters of pores (fenestrae) forming “sieve plates”; the wall is very leaky, letting plasma proteins pass through into the space of Disse, allowing exchange between sinusoidal blood and hepatocytes.
- Bile flows in the opposite direction to blood: blood flows up toward the central vein, while bile flows down toward the bile duct.
- Portal venous flow is set by the vascular resistance of the GI tract and is not controlled by the liver itself, whereas hepatic arterial flow is actively regulated by sympathetic tone (α-adrenoceptor-mediated vasoconstriction of the arterioles).
- Normal liver blood volume is ~500 mL (~10% of total blood volume). In circulatory stress, sympathetic vasoconstriction of the hepatic veins releases up to 350 mL into the systemic circulation within 1-4 minutes.
- Causes: chronic hepatitis B or C infection, iron overload, copper overload, recurrent bile duct injury, alcohol. Liver injury causes accumulation of extracellular matrix proteins, tissue contraction, and fibrous septa containing distorted portal and hepatic venules; this raises vascular resistance, including portal vascular resistance, producing portal hypertension (≥12 mmHg, versus a normal 5-10 mmHg).
- For example: sympathetic diversion of GI blood flow to vital organs, and release of the liver’s reservoir blood (up to 350 mL), both help preserve perfusion and blood volume; however, if hypoperfusion is prolonged, the mucosal barrier fails and endotoxin entry can precipitate septic shock.