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Liver Blood Flow

July 5, 2024

  • Dual Blood Supply:
    • 75-80% by PV
    • 20-25% by HA
  • Hepatic Artery:
    • Supplies 50% of Liver oxygen demand
    • exclusive blood supply to Bile ducts
  • 2.5% of total body weight = 25% of cardiac output
  • Liver Blood Flow = 800-1200ml/min.
  • Sinusoids = 60% of blood volume, 40% in HA,PV,HV
  • COLLATERAL SUPPLY OF LIVER:
    • Phrenic collateral system = from Inferior Phrenic Artery
    • SMA β€”> IPDA β€”> SPDA β€”> GDA β€”> PHA collateral system β‡’ used in appleby procedure

Liver Microcirculation

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  • Hepatic Lobules:
    • The liver is composed of thousands of polyhedral structures called hepatic lobules.
    • Hepatic lobules are the basic functional units of the liver.
    • In some mammals, like pigs, lobules are clearly delimited by connective tissue, but in humans, they have much less connective tissue, making their boundaries harder to distinguish.
  • Structure of Hepatic Lobules:
    • A: Each hepatic lobule has a small central vein at its center, with blood vessels defining the periphery.
      • Peripheral vessels are grouped in connective tissue, forming the portal tracts in the space of Mall.
      • The portal tracts include a branch of the portal vein, the hepatic artery, and the bile ductβ€”collectively known as the portal triad.
    • B: Blood vessels give off sinusoids, which run between plates of hepatocytes and drain into the central vein.
    • C: Micrograph showing the portal triad within the space of Mall.

Structure-Function Conceptual Liver Units:

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  • Consensus:
    • There is no complete consensus on whether the liver's microvascular unit should be referred to as a lobule (centering on a hepatic vein) or an acinus (centering on a "portal triad").
  • Three Conceptual Units:
    • A. Classic Lobule:
      • Emphasizes the endocrine function of hepatocytes as blood flows toward the centrilobular venule.
    • B. Portal Lobule:
      • Emphasizes the hepatocytes exocrine function and the flow of bile toward the bile duct in the portal triad.
      • The area drained by each bile duct is roughly triangular.
    • C. Liver Acinus (Rappaport's Concept):
      • Emphasizes the different oxygen and nutrient contents of blood along the sinusoids.
      • Blood from each portal area supplies cells in two or more classic lobules.
      • Periportal cells of zone I get the most oxygen and nutrients, leading to different metabolic activity compared to pericentral hepatocytes of zone III, which are exposed to the lowest oxygen and nutrient concentrations.

Hepatic Stellate Cells:

  • Fat storing cells, Ito cells, Itocytes
  • Regulate Microcirculation
  • Space of Disse
  • Retinol Metabolism
  • Liver Fibrogenesis

Kupffer Cells:

  • Liver Specific macrophages
  • NO

Control of Liver Blood Flow

  • Hepatic Arterial Buffer Response:
    • The liver cannot regulate the flow of the portal vein.
    • Modulation occurs at the presinusoidal level through the hepatic arterial flow.
  • Hepatic Artery (HA) Function:
    • HA dilates and increases flow when portal flow is decreased, and vice versa.
    • This response is mediated by adenosine and can buffer 25% to 60% of decreased portal flow.
    • H2S also plays a role in this buffering mechanism.
  • Role of Nerves:
    • Partially impaired after liver transplant.
  • Metabolic Control:
    • The liver is NOT controlled by its intrinsic metabolic needs.
  • HA Vasoconstriction:
    • Triggered by hypercarbia and hypoxia.
    • HA has both alpha adrenergic and beta adrenergic receptors.
  • Portal Vein (PV) Receptors:
    • PV contains alpha receptors only. [ β‡’ only high dose epinephrine works on PV]
  • Epinephrine Effects:
    • Low dose epinephrine: Causes hepatic artery dilation and mesenteric vasodilation.
    • High dose epinephrine: Causes constriction in the hepatic artery, portal vein, and mesenteric vessels.
Increase hepatic flow Decrease Hepatic flow
Gastrin Hypercarbia
secretin Hypoxia
CCK Neurokinin
VIP Calcitonin G RP
Glucagon Histamine, Bradykinin
SSRA - Octrotide
  • Food: Increases mesenteric blood flow and portal flow β€”> decrease hepatic arterial flow
  • Anesthesia: Isoflurane seems to have minimal effect on HA & PV flow
  • Fentanyl has very little effect on splanchnic blood flow

HVPG (Hepatic Venous Pressure Gradient) Measurement

  • Transjugular Approach:
    • Used for measuring the pressure gradient between the IVC (Inferior Vena Cava) and PV (Portal Vein).
  • Normal Pressure Gradient:
    • Typically 5 mm Hg between IVC and PV.
  • HVPG Calculation:
    • HVPG = Wedged hepatic venous pressure (WHVP) (sinusoidal pressure) - Free hepatic venous pressure (FHVP).
    • HVPG > 5 mm Hg is indicative of Portal Hypertension (PHTN).

Measurement of Hepatic Venous Pressure

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  • A. Free Hepatic Venous Pressure (FHVP):
    • Measured by maintaining the tip of the catheter free in the hepatic vein at 2 to 4 cm from its opening into the IVC.
  • B. Wedged Hepatic Venous Pressure (WHVP):
    • Measured by occluding the hepatic vein with an angiographic balloon at the catheter's tip.
    • Adequate occlusion is confirmed by slowly injecting 5 mL of contrast dye into the vein with the balloon inflated, showing a typical wedged pattern distal to the balloon.
  • C. Measurement Challenges:
    • Washout of contrast dye through communications with other hepatic veins can prevent a correct measurement of the hepatic venous pressure.
  • D. Pressure Tracing:
    • Typical pressure measurements in the hepatic vein are obtained using a multichannel recorder and adequately calibrated transducers.

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Ischemia to Liver

  • Shock:
    • Decreased PV flow; HA flow is maintained.
    • Shock Liver: Characterized by centrilobular necrosis.
    • Acute phase proteins are increased: CRP, fibrinogen, albumin, transferrin.
  • Ischemia-reperfusion injury:
    • Nitric Oxide (NO) protects the liver.

Liver Atrophy

  • Portal Vein Occlusion:
    • Leads to liver atrophy due to a decrease in hepatotrophic substances.
    • Liver will not necrose due to maintained HA flow.
    • Mechanism involves both necrosis and apoptosis.
  • Hepatic Artery Ligation:
    • Outcome depends on collateral flow:
      • Necrosis: If no collateral flow.
      • Atrophy: If collateral flow is present; seldom happens.

Bile Duct Obstruction

  1. Chronic Biliary Obstruction:
    • Decrease in hepatic blood flow.
    • May persist for the long term.
    • Can lead to portal hypertension and secondary biliary cirrhosis.
    • Risk of shock after sudden decompression.
    • Blood flow may not normalize for up to 1-5 years after decompression.
  2. Acute Obstruction:
    • Causes a reflex increase in blood flow due to compression of the PV via BD dilation.

Liver Resection and Regeneration

  • Liver Resection:
    • After regeneration, there is portal hyperperfusion through the smaller liver mass.
    • Results in doubling of portal vein flow in remnant tissue.

Liver Transplantation

  • Hepatic Arterial Buffer Response (HABR):
    • Conserved after liver transplantation due to adenosine.
    • Total liver blood flow remains elevated, with increased PV flow.
    • Loss of sympathetic control post-transplantation.

Small for Size Syndrome

  • Characterized by increased portal flow through a small remnant with a marked decrease in arterial inflow (intact HABR).
  • Splenic artery steal phenomenon may occur.
  • Ligation of the splenic artery may be necessary.
  • Results in cholestasis and liver dysfunction.

Portal Hypertension

  • Increased portal pressure.
  • Diminished portal blood flow with increased arterial flow (due to HABR).
  • Associated with hyperdynamic circulation (low peripheral vascular resistance).
  • Nitric Oxide (NO) increases mesenteric flow.
  • May involve intrahepatic and extrahepatic shunting.

Bullet points

  • Low dose epinephrine cause hepatic artery dilatation and mesenteric vasodilation
  • high dose epinephrine cause constriction
  • All the gut hormones increase liver blood flow except Insulin, which has no effect on liver blood flow
  • prostacyclin doesnt effect HA flow but increses portal flow
  • vasopressin decreases portal flow by decreasing the inflow to mesenteric vasculature through mesenteric arterial vasoconstriction but has a variable effect on HA

Splenic Artery Steal Phenomenon in Small-for-Size Syndrome (SFSS) for Liver

Definition:

  • Splenic Artery Steal Phenomenon refers to the diversion of blood flow away from the hepatic artery towards the splenic artery, reducing the effective blood supply to the liver. This can occur in the context of Small-for-Size Syndrome (SFSS) after liver transplantation or resection.

Context in SFSS:

  • Small-for-Size Syndrome (SFSS) is a condition that occurs when the transplanted liver graft or the remaining liver after resection is too small relative to the metabolic demands of the recipient. It is characterized by liver dysfunction, including jaundice, coagulopathy, and ascites.
  • In this syndrome, the reduced liver volume can lead to insufficient liver perfusion and function.

Mechanism:

  • The splenic artery may "steal" blood that would otherwise flow to the hepatic artery, leading to hepatic hypoperfusion.
  • This phenomenon is exacerbated in SFSS due to the already compromised liver size and function, further impairing liver regeneration and function.

Clinical Significance:

  • Splenic Artery Steal Phenomenon is a critical factor in the pathogenesis of SFSS. It contributes to portal hypertension, impaired liver regeneration, and subsequent graft failure or poor recovery after liver surgery.

Management:

  • Interventions may include splenic artery embolization or modification of the portal flow to reduce the impact of the steal phenomenon and improve liver perfusion.

Liver Blood flow Physiology

Portal Vein (PV):

  • The portal vein is a valveless, low-pressure system that plays a critical role in delivering nutrient-rich blood from the gastrointestinal tract and spleen to the liver.
  • In the hepatic sinusoids, the blood flow from the portal vein is constant and minimal.

Hepatic Artery (HA):

  • The hepatic artery supplies oxygen-rich blood to the liver.
  • In the sinusoids, the blood flow from the hepatic artery is pulsatile and low volume.
  • HA and PV flow inversely vary in the sinusoids, meaning when one increases, the other decreases.

Hepatic Sinusoids:

  • Diameter: 4-15 ΞΌm, but they can expand up to 10 times their size.
  • Pressure: They operate at a low pressure of 2-3 mm Hg.
  • Structural Features:
    • Absence of Basement Membrane: This allows for the free passage of plasma but restricts the passage of cells.
    • Endothelial Lining: The endothelial cells have flattened processes with small fenestrae (pores) ranging from 50 to 175 nm in diameter. These pores form clusters of 10 to 50, creating a "sieve" effect.
    • The diameter of these fenestrae decreases, and their frequency increases from the periportal to the centrilobular zones, leading to higher porosity in the centrilobular area.

Blood and Bile Flow:

  • Blood and bile flow in opposite directions within the liver. Blood flows from the portal vein and hepatic artery through the sinusoids towards the central vein, while bile flows from the hepatocytes towards the bile ducts in the portal triad.

Control of Hepatic Blood Flow:

  • Hepatic blood flow is primarily regulated by intrinsic mechanisms and is not significantly controlled by extrinsic innervation.

Summary:

  • Portal Vein (PV): Valveless, low pressure, constant minimal flow in sinusoids.
  • Hepatic Artery (HA): Pulsatile, low volume flow, inversely varies with PV flow.
  • Hepatic Sinusoids: Low-resistance, low-pressure system, with unique endothelial lining and fenestrae, facilitating efficient nutrient and waste exchange.
  • Blood and Bile Flow: Opposite directions, critical for liver function.

Multiple Choice Question

Answer:

  • Correct Answer: D. HA flow in sinusoids is constant

Explanation:

  • A: True. The portal vein is a valveless low-pressure system.
  • B: True. HA and PV flow in sinusoids is inversely related.
  • C: True. Hepatic blood flow is primarily regulated by intrinsic mechanisms and not significantly controlled by extrinsic innervation.
  • D: False. HA flow in the sinusoids is pulsatile and low volume, not constant.

Liver Blood Flow

Key Points

  1. Total Liver Blood Flow (LBF):
    • Ranges between 800 to 1200 mL/min.
    • Equivalent to approximately 100 mL/min per 100 g of liver wet weight.
  2. Compensation During Bleeding:
    • The liver can compensate up to 25% during bleeding.
  3. Blood Volume Distribution:
    • Sinusoids hold 60% of the blood volume.
    • The remaining 40% is in large vessels (Hepatic Artery (HA), Portal Vein (PV), and Hepatic Veins (HV)).
  4. Liver Mass and Cardiac Output:
    • Liver mass constitutes approximately 2.5% of the total body weight.
    • The liver receives nearly 25% of the cardiac output.
  5. Blood Supply to Intrahepatic Bile Ducts:
    • The HA provides the exclusive blood supply to the intrahepatic bile ducts through the peribiliary plexus.
  6. Oxygen Saturation in Portal Blood:
    • During fasting states, the oxygen saturation in the portal blood approaches 85%, which is greater than other systemic veins.
    • In resting states, the liver accounts for approximately 20% of the total oxygen consumption of the body.
  7. Pressure Conditions:
    • In normal conditions, the free pressure in the hepatic veins (HVs) and inferior vena cava (IVC) is 1 to 2 mm Hg.
    • This pressure is 1 to 5 mm Hg lower than the pressure measured in the sinusoids and PV.

Summary:

  • Liver Blood Flow: 800-1200 mL/min, compensates up to 25% during bleeding.
  • Blood Volume Distribution: 60% in sinusoids, 40% in large vessels.
  • Liver Mass and Cardiac Output: 2.5% of body weight, receives 25% of cardiac output.
  • Blood Supply to Bile Ducts: Exclusive via HA.
  • Oxygen Saturation: Higher in portal blood during fasting.
  • Pressure Conditions: Lower in HVs and IVC compared to sinusoids and PV.

Multiple Choice Question

Answer:

  • Correct Answer: F. During fasting states, the oxygen saturation in the portal blood approaches 85%, which is greater than that of systemic veins.

Hepatic Arterial Buffer Response (HABR)

Key Points

  1. Discovery:
    • First described by Lautt.
  2. Function:
    • HABR represents the ability of the hepatic artery (HA) to produce compensatory flow changes at the presinusoidal level in response to changes in portal vein (PV) flow.
    • This mechanism helps maintain a stable blood flow to the liver despite fluctuations in PV flow.
  3. Regulation:
    • HABR is regulated via adenosine, not nitric oxide (NO).
  4. Compensatory Capacity:
    • Capable of buffering 25 to 60% of decreases in PV flow.
    • This ensures that the liver receives an adequate blood supply even when PV flow is reduced.

Summary:

  • Discovery: First described by Lautt.
  • Function: Compensatory flow changes in HA in response to PV flow changes.
  • Regulation: Via adenosine.
  • Compensatory Capacity: Buffers 25 to 60% of decreases in PV flow.

Multiple Choice Question

Answer:

  • Correct Answer: C. HABR is regulated via adenosine, not NO.

Hepatic Blood Flow Responses

Condition PV Flow HA Flow
Metabolic Acidosis Increase Decrease
Metabolic Alkalosis No Effect No Effect
Hypercarbia Increase Decrease
Hypocarbia Decreases Decreases
Meal Increases Decreases
Vasopressin Decreases Variable
Angiotensin Decreases Decreases

Additional Note:

The hepatic arterial buffer response (HABR) is a key mechanism in maintaining adequate liver perfusion. When portal vein (PV) flow decreases, the hepatic artery (HA) compensates by increasing its flow, and vice versa. This regulation primarily occurs through adenosine signaling.

  • Hypercarbia and Metabolic Acidosis: These conditions lead to vasodilation and increased blood flow in the PV, while compensatory mechanisms reduce HA flow.
  • Hypocarbia: Causes vasoconstriction, decreasing blood flow in both PV and HA.
  • Meals: Increase metabolic activity in the gut, leading to increased PV flow due to enhanced nutrient absorption, while HA flow decreases to maintain overall liver perfusion.
  • Hormones:
    • Vasopressin: Can cause vasoconstriction, reducing PV flow with variable effects on HA flow.
    • Angiotensin: Generally causes vasoconstriction, reducing both PV and HA flow.

Hormonal Influences:

  • Vasodilators:
    • Gastrin, secretin, cholecystokinin, and vasoactive intestinal peptide cause vasodilation of the HA.
    • Glucagon increases hepatic blood flow due to its vasodilatory action on the mesenteric vasculature.
  • Vasoconstrictors:
    • Serotonin mediates vasoconstriction of portal radicles.

Summary:

  • Hypercarbia and Acidosis: Increase PV, decrease HA flow.
  • Alkalosis: No effect on PV and HA flow.
  • Hypocarbia: Decreases both PV and HA flow.
  • Meal: Increases PV, decreases HA flow.
  • Vasopressin: Decreases PV, variable effect on HA flow.
  • Angiotensin: Decreases both PV and HA flow.

Multiple Choice Question

Answer:

  • Correct Answer: D metabolic alkalosis has no effect on PV and HA flow.