50 Liver Structure and Function0
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Questions and Answers

What is the function of bile formed by hepatocytes?

  • To filter toxins from blood
  • To store glucose
  • To facilitate fat digestion (correct)
  • To aid in protein synthesis

    • Which structure is described as a small duct that forms from canaliculi and joins to form part of the bile drainage system?

  • Ductule (correct)
  • Gall bladder
  • Central vein
  • Hepatic duct

    • In the context of liver micro-anatomy, what does the acinus refer to?

  • A structural unit of the gall bladder
  • Hepatocytes and sinusoids from two adjacent lobules supplied by one portal tract (correct)
  • The central vein of the liver
  • The outer layer of liver tissue

    • Which zone of the acinus is most severely affected by ischaemic or toxic injury?

    <p>Zone 3</p> Signup and view all the answers

    What primarily causes chronic passive venous congestion of the liver?

    <p>Right heart failure</p> Signup and view all the answers

    What are the primary blood supplies to the liver?

    <p>Portal vein and hepatic artery</p> Signup and view all the answers

    Which of the following is NOT a common cause of liver damage?

    <p>Cardiac failure</p> Signup and view all the answers

    What distinguishes compensated cirrhosis from decompensated cirrhosis?

    <p>Presence of ascites</p> Signup and view all the answers

    Which cell type in the liver helps in the regeneration process?

    <p>Hepatocytes</p> Signup and view all the answers

    Portal hypertension can develop due to which of the following conditions?

    <p>Fibrosis or cirrhosis</p> Signup and view all the answers

    What is the typical weight of a healthy adult liver?

    <p>1.5 kg</p> Signup and view all the answers

    The Space of Disse in the liver is located between which structures?

    <p>Sinusoids and hepatocytes</p> Signup and view all the answers

    Which condition is commonly associated with non-alcoholic fatty liver disease?

    <p>Metabolic syndrome</p> Signup and view all the answers

    What is the most common appearance of chronic passive venous congestion of the liver?

    <p>Nutmeg liver</p> Signup and view all the answers

    Which condition is indicated by obstruction to venous outflow from the liver?

    <p>Budd Chiari syndrome</p> Signup and view all the answers

    Which factor does NOT increase susceptibility to ischaemic injury to the liver?

    <p>Active liver regeneration</p> Signup and view all the answers

    What is the potential outcome of extensive liver damage?

    <p>Acute liver failure</p> Signup and view all the answers

    Which type of liver injury results in massive hepatic necrosis?

    <p>Extensive damage</p> Signup and view all the answers

    What is primarily synthesized by the liver?

    <p>Plasma proteins</p> Signup and view all the answers

    Which statement about ischaemic hepatitis is true?

    <p>It exhibits marked elevation of liver blood tests.</p> Signup and view all the answers

    What defines chronic liver disease?

    <p>Ongoing insult for more than 6 months</p> Signup and view all the answers

    What is the term used for interface inflammation that indicates 'piecemeal necrosis'?

    <p>Necroinflammation</p> Signup and view all the answers

    Which of the following best describes the stage of fibrosis when fibrous bands surround regenerative nodules and the architecture is diffusely distorted?

    <p>Cirrhosis</p> Signup and view all the answers

    What is a key structural change in the liver due to cirrhosis?

    <p>Obliteration of veins within the liver</p> Signup and view all the answers

    Which factor most directly contributes to the development of portal hypertension in cirrhosis?

    <p>Increased hepatic resistance to portal blood flow</p> Signup and view all the answers

    What is the histological feature observed in cirrhosis when using a trichrome stain?

    <p>Fibrous bands separating regenerative nodules</p> Signup and view all the answers

    In cirrhosis, what compensatory mechanism occurs due to splanchnic vasodilation?

    <p>Increased hepatic venous pressure gradient</p> Signup and view all the answers

    Which pattern of fibrosis is characterized by connections between portal tracts and central veins?

    <p>Bridging fibrosis</p> Signup and view all the answers

    What effect does vascular alterations due to cirrhosis have on liver function?

    <p>Increased risk of hepatocellular carcinoma</p> Signup and view all the answers

    What happens to the blood flow in the portal system when there is increased blood flow to the intestines?

    <p>More blood must leave the intestines.</p> Signup and view all the answers

    What contributes to the development of ascites in portal hypertension?

    <p>Higher hydrostatic pressure in peritoneal vessels.</p> Signup and view all the answers

    What is a potential risk associated with the development of shunts in portal hypertension?

    <p>Increased risk of hepatic encephalopathy.</p> Signup and view all the answers

    Which of the following is NOT a characteristic of decompensated cirrhosis?

    <p>Lack of biochemical abnormalities.</p> Signup and view all the answers

    What triggers might lead to the decompensation of compensated cirrhosis?

    <p>Bleeding and infection.</p> Signup and view all the answers

    In which condition is there a block to blood flow due to liver damage?

    <p>Cirrhosis.</p> Signup and view all the answers

    What is one effect of sodium and water retention in patients with portal hypertension?

    <p>Increased hydrostatic pressure in vessels.</p> Signup and view all the answers

    Which mechanism is involved in the body’s compensation during widespread vasodilation in portal hypertension?

    <p>Stimulation of antidiuretic hormone (ADH) secretion.</p> Signup and view all the answers

    Which of the following best describes the concept of cirrhosis?

    <p>An irreversible scarring of the liver leading to loss of function.</p> Signup and view all the answers

    Which statement accurately differentiates between compensated and decompensated cirrhosis?

    <p>Decompensated cirrhosis may present with ascites and variceal hemorrhage.</p> Signup and view all the answers

    Which of the following is least likely to contribute to the development of portal hypertension?

    <p>Increased blood flow from the hepatic artery to the liver.</p> Signup and view all the answers

    What role do hepatic stellate cells play in the liver’s response to injury?

    <p>They contribute to fibrosis by producing collagen when activated.</p> Signup and view all the answers

    What is the significance of the Space of Disse in liver structure?

    <p>It facilitates exchange between sinusoidal blood and hepatocytes.</p> Signup and view all the answers

    Which pattern of liver damage is most commonly associated with chronic alcohol consumption?

    <p>Alcoholic steatosis and cirrhosis.</p> Signup and view all the answers

    Which of the following processes directly contributes to ascites formation in liver disease?

    <p>Increased hydrostatic pressure in the portal circulation.</p> Signup and view all the answers

    Which condition is primarily characterized by retained bile salts causing liver injury?

    <p>Chronic biliary disease.</p> Signup and view all the answers

    Which condition is characterized by elevation of liver blood tests due to ischaemic injury?

    <p>Shock liver</p> Signup and view all the answers

    What is a common gross appearance of chronic passive venous congestion of the liver?

    <p>Nutmeg liver</p> Signup and view all the answers

    Which of the following is not a trigger for liver cell injury?

    <p>Fructose metabolism</p> Signup and view all the answers

    What can result from ongoing insult to the liver over an extended period?

    <p>Chronic liver disease</p> Signup and view all the answers

    What defines the grade of liver damage during assessment?

    <p>The extent of inflammation and necrosis</p> Signup and view all the answers

    How does the liver typically respond to acute damage?

    <p>Undergoes regeneration if damage is not extensive</p> Signup and view all the answers

    Which liver function includes the excretion of bilirubin?

    <p>Bile formation</p> Signup and view all the answers

    What is a potential consequence of massive hepatic necrosis?

    <p>Acute liver failure</p> Signup and view all the answers

    What is the 1 year mortality rate for patients with compensated cirrhosis who also have varices?

    <p>4%</p> Signup and view all the answers

    What is the median survival time for patients diagnosed with decompensated cirrhosis?

    <p>1.6 years</p> Signup and view all the answers

    Which complication is least likely to develop in patients with compensated cirrhosis?

    <p>Death</p> Signup and view all the answers

    How does the development of complications in chronic liver disease affect patient prognosis?

    <p>Leads to a significant decrease in survival time</p> Signup and view all the answers

    Which of the following is not typically associated with decompensation in chronic liver disease?

    <p>Chronic inflammation</p> Signup and view all the answers

    Which statement best characterizes the outcomes of hepatic decompensation in cirrhosis?

    <p>Decompensated cirrhosis can result from variceal hemorrhage.</p> Signup and view all the answers

    Which of the following features greatly increases the risk of mortality in decompensated liver disease?

    <p>Presence of ascites</p> Signup and view all the answers

    What is a major consequence of developing decompensated cirrhosis?

    <p>Higher likelihood of liver transplantation</p> Signup and view all the answers

    What effect does portal hypertension have on the peritoneal cavity?

    <p>Promotes preferential accumulation of fluid</p> Signup and view all the answers

    Which compensatory mechanism is activated due to widespread vasodilation in portal hypertension?

    <p>Activation of the renin-angiotensin-aldosterone system</p> Signup and view all the answers

    What complication may arise due to intrahepatic porto-systemic shunts resulting from portal hypertension?

    <p>Worsening liver function due to shunted blood</p> Signup and view all the answers

    What triggers the decompensation of compensated cirrhosis?

    <p>Infection, bleeding, and dehydration</p> Signup and view all the answers

    What is a common outcome of sodium and water retention in individuals with portal hypertension?

    <p>Development of ascites</p> Signup and view all the answers

    What describes the vascular changes in the liver due to cirrhosis?

    <p>Obliteration of veins within the liver</p> Signup and view all the answers

    What underlying issue contributes to the higher mean hydrostatic pressure seen in portal hypertension?

    <p>Reduced blood flow out of the liver</p> Signup and view all the answers

    Which characteristic is indicative of bridging fibrosis?

    <p>Fibrosis connecting portal tracts to central veins</p> Signup and view all the answers

    What is a main consequence of portal hypertension in cirrhosis?

    <p>Increased hepatic resistance to blood flow</p> Signup and view all the answers

    What is primarily affected due to cirrhosis in the context of blood flow dynamics?

    <p>Obstruction to blood flow through the liver</p> Signup and view all the answers

    What consequence may result from the capillarisation of sinusoids in the context of portal hypertension?

    <p>Decreased functional liver tissue perfusion</p> Signup and view all the answers

    Which feature is observed in cirrhosis when using H&E staining?

    <p>Nodules of regenerative parenchyma separated by fibrous bands</p> Signup and view all the answers

    How does splanchnic vasodilation affect the cardiovascular system in cirrhosis?

    <p>Leads to hyperdynamic circulation with increased cardiac output</p> Signup and view all the answers

    What does the presence of regenerative nodules and fibrous septa indicate in liver histology?

    <p>End-stage liver disease or cirrhosis</p> Signup and view all the answers

    What is the role of the hepatic venous pressure gradient (HVPG) in portal hypertension?

    <p>Indicates increased resistance to portal flow</p> Signup and view all the answers

    Which histological feature helps to identify the degree of fibrosis in liver biopsy?

    <p>Specific scoring systems that assess grade and stage</p> Signup and view all the answers

    Study Notes

    Liver Structure and Blood Supply

    • Liver weighs approximately 1.5kg and possesses a significant functional reserve
    • Liver cells are capable of regeneration
    • Liver has a dual blood supply with both the hepatic artery and portal vein delivering blood
    • Blood flows through sinusoids, which are blood spaces separating plates of hepatocytes
    • Sinusoids are lined by fenestrated endothelium and Kupffer cells (macrophages)
    • The Space of Disse lies between sinusoids and hepatocytes and contains hepatic stellate cells
    • Venous drainage occurs via the hepatic vein to the inferior vena cava (IVC) to the right ventricle (RV)

    Liver Function

    • Liver synthesizes most plasma proteins, including those involved in clotting
    • Liver produces bile for excretion of bilirubin and digestion of fats and fat-soluble vitamins (ADEK)
    • Liver detoxifies both endogenous and exogenous compounds
    • Liver plays a role in intermediary metabolism, altering and storing substances
    • Liver participates in immune functions, acting as a buffer between the gut and the rest of the body
    • Liver stores both normal and abnormal substances
    • Liver performs hematopoiesis (blood cell production) in the fetus and infant

    Liver Injury

    • Liver has a reserve and regenerative capacity, allowing for recovery from acute damage in many cases
    • Extensive acute damage can lead to acute liver failure
    • Chronic liver damage occurs with ongoing insult and is defined as damage lasting over six months
    • Chronic damage can lead to fibrosis and progression to cirrhosis
    • Co-existing causes of liver damage can exacerbate the condition
    • Patterns of cell damage can vary from single-cell death (apoptosis) to massive hepatic necrosis
    • Cell injury can be triggered by direct cytotoxic effects, damage to hepatocytes rendering them antigenic (e.g., HBV), or damage to cells perceived as antigenic (e.g., autoimmune hepatitis)

    Assessment of Liver Damage

    • Inflammation and necrosis are graded based on extent of damage
    • Inflammation can occur in the portal/periportal area or in the lobules (parenchyma)
    • Piecemeal necrosis describes a specific pattern of interface inflammation
    • Necrosis can be present as single-cell death, spotty necrosis, or bridging necrosis
    • Predominant inflammatory cell type is influenced by the cause of liver damage
    • Fibrosis is staged based on degree and extent
    • Fibrosis can occur in portal areas, periportal areas, and as bridging fibrosis (portal tract to portal tract or portal tract to central vein)
    • Cirrhosis represents the end-stage of fibrosis
    • Complex scoring systems are used to assess liver biopsy specimens, considering both grade and stage

    Cirrhosis

    • Cirrhosis is characterized by diffuse distortion of liver architecture, with fibrous bands, regenerative nodules, and distorted vascular relationships
    • Cirrhosis impairs liver function, contributing to portal hypertension and increasing the risk of hepatocellular carcinoma
    • Vascular changes in cirrhosis include obliteration or thrombosis of veins, formation of collateral channels, and capillarization of sinusoids, leading to an increased hepatic venous pressure gradient (HVPG)
    • Cirrhosis represents the end-stage of chronic liver disease, diminishing liver reserve

    Portal Hypertension

    • Increased resistance to portal blood flow in cirrhosis initiates portal hypertension, raising HVPG
    • Splanchnic vasodilatation (via nitric oxide, NO) further contributes to portal hypertension
    • Splanchnic vasodilatation reduces total peripheral resistance (TPR) and blood pressure
    • The body compensates with increased cardiac output, leading to a hyperdynamic circulation in cirrhosis
    • Splanchnic vasodilatation triggers compensatory mechanisms, including activation of the renin-angiotensin-aldosterone system, ADH secretion, sodium and water retention, and renal vasoconstriction

    Ascites

    • Sodium and water retention in the setting of portal hypertension can lead to ascites
    • Ascites occurs due to fluid leakage from peritoneal vessels, increased hydrostatic pressure, and decreased oncotic pressure (low albumin)

    Portal Hypertension Shunts

    • To decompress portal hypertension, collateral channels form both within and outside the liver
    • Therapeutic shunts, such as transjugular intrahepatic porto-systemic shunts (TIPS), can be inserted
    • Shunting bypasses the liver, further reducing liver function and exacerbating damage

    Compensated vs. Decompensated Cirrhosis

    • Compensated cirrhosis may not manifest with biochemical or radiological abnormalities or signs of chronic liver disease or portal hypertension
    • Even with compensated cirrhosis, further injury (infection, bleeding, hypotension, alcohol, medications, dehydration, trauma, surgery) can trigger decompensation
    • Decompensated cirrhosis is characterized by complications including ascites, hepatic encephalopathy, variceal hemorrhage, hepatorenal syndrome (HRS), jaundice, and infections

    Liver Structure & Function

    • The liver weighs about 1.5kg
    • It has a large functional reserve
    • The liver contains stable cells and is able to regenerate
    • The liver's blood supply is dual: hepatic artery and portal vein
    • Blood travels through sinusoids, which are blood spaces separating plates of hepatocytes
    • Sinusoids are lined by fenestrated endothelium and macrophages (Kupffer cells)
    • Space of Disse sits between sinusoids and hepatocytes and contains hepatic stellate cells
    • Venous drainage is via the hepatic vein to the inferior vena cava (IVC) to the right ventricle (RV)
    • Main functions include:
      • Synthesis of most plasma proteins
      • Clotting factors
      • Bile formation
      • Bilirubin: excretion
        • Bile Salts -- digestion
        • Fat/fat-soluble vitamins ADEK
      • Detoxification of endogenous/exogenous compounds
      • Intermediary metabolism
      • Immune function as a buffer between the gut and rest of the body
      • Storage - normal/abnormal
      • Haematopoiesis (foetal/infant)

    Liver Damage

    • The liver has reserve and regenerative capacity
    • Possible outcomes of acute liver damage depend on the degree of damage
      • Extensive damage may result in acute liver failure
      • Transient damage may lead to recovery
      • On-going or repeated insult leads to chronic damage
    • Chronic liver disease is defined as damage lasting longer than 6 months
      • Fibrosis develops and progresses to cirrhosis
    • The causes of liver damage may coexist, be superimposed, or potentiate each other
    • Patterns of cell damage and death include different types of cell injury (reversible or irreversible)
    • Triggers for injury include:
      • Direct cytopathic/cytotoxic/ischaemic effects
      • Damage to hepatocytes rendered antigenic (e.g. HBV)
      • Damage to cells perceived as antigenic (e.g. autoimmune hepatitis)
    • Different degrees of injury include:
      • Single cell death (apoptosis)
      • Small group cell death (spotty necrosis)
      • Large confluent group cell death (bridging necrosis)
      • Massive hepatic necrosis

    Assessing Liver Damage

    • Inflammation and/or necrosis is assessed by its extent, termed "grade"
    • 炎症是否属于门脉周围、门脉或小叶性？有多少门脉周围、门脉或小叶性炎症？界面炎症= “片状坏死”
    • Is necrosis present? Single cells, spotty or bridging?
    • Predominant inflammatory cell type depends on aetiology, not whether the disease is acute or chronic in duration.
    • Fibrosis is assessed by its degree and extent, termed "stage"
      • Portal fibrosis
      • Periportal fibrosis
      • Bridging fibrosis: portal to portal tract or portal to central vein
      • Cirrhosis
    • Liver biopsy is used for complex scoring systems to assess grade and stage independently

    Cirrhosis

    • A diffuse distortion of liver architecture
    • Fibrous bands/septa surround regenerative nodules
    • Distorted vascular relationships lead to:
      • Decreased liver function
      • Portal hypertension
      • Risk of hepatocellular carcinoma

    Portal Hypertension

    • Results from increased hepatic resistance to portal blood flow, and a rise in HVPG (hepatic venous pressure gradient)
    • Augmented by splanchnic vasodilatation, which increases portal blood flow
      • Splanchnic vasodilatation also lowers total peripheral resistance (TPR) and blood pressure (BP)
    • A compensatory increase in cardiac output leads to the hyperdynamic circulation of cirrhosis
    • Splanchnic vasodilatation triggers compensatory mechanisms
      • Activation of the renin-angiotensin-aldosterone system
      • Stimulation of antidiuretic hormone (ADH) secretion
      • Sodium and water retention
      • Reflex renal vasoconstriction = reduced perfusion and glomerular filtration rate (GFR), increasing the risk of hepatorenal syndrome (HRS)

    Ascites

    • Sodium and water retention, related to portal hypertension, preferentially accumulates fluid in the peritoneal cavity.
    • Fluid leaks from peritoneal vessels
    • Higher mean hydrostatic pressure due to portal hypertension
    • Lower oncotic pressure to keep fluid in due to low albumin

    Portal Hypertension & Shunts

    • Collaterals develop to decompress portal hypertension:
      • Intrahepatic porto-systemic shunts/collaterals
      • Extrahepatic porto-systemic anastomoses dilate
      • Therapeutic insertion of a shunt (TIPS -- transjugular intrahepatic porto-systemic shunt)
    • "Shunted" blood bypasses the liver, further reducing liver function and increasing the risk of hepatic encephalopathy
    • "Capillarisation" of sinusoids exacerbates this process
    • Shunting reduces perfusion of the liver, worsening the damage

    Compensated vs. Decompensated Cirrhosis

    • Compensated (Silent) Cirrhosis
      • May or may not have biochemical/radiological abnormality
      • May or may not have signs of chronic liver disease/portal hypertension
      • May or may not have varices on OGD (gastroscopy)
      • Potential for instability, with further injury triggering decompensation (infection, bleeding, hypotension, alcohol, medications, dehydration, trauma, surgery)
    • Decompensated Cirrhosis
      • Key complications:
        • Ascites (may become refractory to treatment)
        • Hepatic encephalopathy
        • Variceal hemorrhage
        • Hepatorenal syndrome (HRS)
        • Jaundice
        • Infection (esp. spontaneous bacterial peritonitis)
        • Hepatocellular carcinoma
    • Decompensation significantly affects prognosis
      • 1-year mortality:
        • Compensated - 1%
        • Compensated with varices - 4%
        • Decompensated, ascites - 20%
        • Decompensated, other features - >50%

    Natural History of Chronic Liver Disease

    • Decompensation affects prognosis
    • Progression from chronic liver disease to compensated cirrhosis to decompensated cirrhosis can lead to death.
      • Median compensated cirrhosis survival is approximately 9 years.
      • Median decompensated cirrhosis survival is approximately 1.6 years.
      • Variceal hemorrhage, ascites, encephalopathy, and jaundice are all common complications.
      • Orthotopic liver transplant (OLT) may be a treatment option.
    • Survival times in cirrhosis are significantly impacted by decompensation.
      • The median survival for patients with cirrhosis overall is 9 years.
      • For patients with decompensated cirrhosis, the median survival is 1.6 years.

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