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?

Zone 3 Signup and view all the answers

What primarily causes chronic passive venous congestion of the liver?

Right heart failure Signup and view all the answers

What are the primary blood supplies to the liver?

Portal vein and hepatic artery Signup and view all the answers

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

Cardiac failure Signup and view all the answers

What distinguishes compensated cirrhosis from decompensated cirrhosis?

Presence of ascites Signup and view all the answers

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

Hepatocytes Signup and view all the answers

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

Fibrosis or cirrhosis Signup and view all the answers

What is the typical weight of a healthy adult liver?

1.5 kg Signup and view all the answers

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

Sinusoids and hepatocytes Signup and view all the answers

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

Metabolic syndrome Signup and view all the answers

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

Nutmeg liver Signup and view all the answers

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

Budd Chiari syndrome Signup and view all the answers

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

Active liver regeneration Signup and view all the answers

What is the potential outcome of extensive liver damage?

Acute liver failure Signup and view all the answers

Which type of liver injury results in massive hepatic necrosis?

Extensive damage Signup and view all the answers

What is primarily synthesized by the liver?

Plasma proteins Signup and view all the answers

Which statement about ischaemic hepatitis is true?

It exhibits marked elevation of liver blood tests. Signup and view all the answers

What defines chronic liver disease?

Ongoing insult for more than 6 months Signup and view all the answers

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

Necroinflammation 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?

Cirrhosis Signup and view all the answers

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

Obliteration of veins within the liver Signup and view all the answers

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

Increased hepatic resistance to portal blood flow Signup and view all the answers

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

Fibrous bands separating regenerative nodules Signup and view all the answers

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

Increased hepatic venous pressure gradient Signup and view all the answers

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

Bridging fibrosis Signup and view all the answers

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

Increased risk of hepatocellular carcinoma 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?

More blood must leave the intestines. Signup and view all the answers

What contributes to the development of ascites in portal hypertension?

Higher hydrostatic pressure in peritoneal vessels. Signup and view all the answers

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

Increased risk of hepatic encephalopathy. Signup and view all the answers

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

Lack of biochemical abnormalities. Signup and view all the answers

What triggers might lead to the decompensation of compensated cirrhosis?

Bleeding and infection. Signup and view all the answers

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

Cirrhosis. Signup and view all the answers

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

Increased hydrostatic pressure in vessels. Signup and view all the answers

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

Stimulation of antidiuretic hormone (ADH) secretion. Signup and view all the answers

Which of the following best describes the concept of cirrhosis?

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

Which statement accurately differentiates between compensated and decompensated cirrhosis?

Decompensated cirrhosis may present with ascites and variceal hemorrhage. Signup and view all the answers

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

Increased blood flow from the hepatic artery to the liver. Signup and view all the answers

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

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

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

It facilitates exchange between sinusoidal blood and hepatocytes. Signup and view all the answers

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

Alcoholic steatosis and cirrhosis. Signup and view all the answers

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

Increased hydrostatic pressure in the portal circulation. Signup and view all the answers

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

Chronic biliary disease. Signup and view all the answers

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

Shock liver Signup and view all the answers

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

Nutmeg liver Signup and view all the answers

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

Fructose metabolism Signup and view all the answers

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

Chronic liver disease Signup and view all the answers

What defines the grade of liver damage during assessment?

The extent of inflammation and necrosis Signup and view all the answers

How does the liver typically respond to acute damage?

Undergoes regeneration if damage is not extensive Signup and view all the answers

Which liver function includes the excretion of bilirubin?

Bile formation Signup and view all the answers

What is a potential consequence of massive hepatic necrosis?

Acute liver failure Signup and view all the answers

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

4% Signup and view all the answers

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

1.6 years Signup and view all the answers

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

Death Signup and view all the answers

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

Leads to a significant decrease in survival time Signup and view all the answers

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

Chronic inflammation Signup and view all the answers

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

Decompensated cirrhosis can result from variceal hemorrhage. Signup and view all the answers

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

Presence of ascites Signup and view all the answers

What is a major consequence of developing decompensated cirrhosis?

Higher likelihood of liver transplantation Signup and view all the answers

What effect does portal hypertension have on the peritoneal cavity?

Promotes preferential accumulation of fluid Signup and view all the answers

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

Activation of the renin-angiotensin-aldosterone system Signup and view all the answers

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

Worsening liver function due to shunted blood Signup and view all the answers

What triggers the decompensation of compensated cirrhosis?

Infection, bleeding, and dehydration Signup and view all the answers

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

Development of ascites Signup and view all the answers

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

Obliteration of veins within the liver Signup and view all the answers

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

Reduced blood flow out of the liver Signup and view all the answers

Which characteristic is indicative of bridging fibrosis?

Fibrosis connecting portal tracts to central veins Signup and view all the answers

What is a main consequence of portal hypertension in cirrhosis?

Increased hepatic resistance to blood flow Signup and view all the answers

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

Obstruction to blood flow through the liver Signup and view all the answers

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

Decreased functional liver tissue perfusion Signup and view all the answers

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

Nodules of regenerative parenchyma separated by fibrous bands Signup and view all the answers

How does splanchnic vasodilation affect the cardiovascular system in cirrhosis?

Leads to hyperdynamic circulation with increased cardiac output Signup and view all the answers

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

End-stage liver disease or cirrhosis Signup and view all the answers

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

Indicates increased resistance to portal flow Signup and view all the answers

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

Specific scoring systems that assess grade and stage 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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Explore the intricate structure and vital functions of the liver in this quiz. Learn about its unique blood supply, regenerative capabilities, and essential roles in metabolism and detoxification. Test your knowledge on how liver functions support overall health and well-being.