Liver Anatomy and Bile Drainage

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Questions and Answers

What is the function of the common bile duct in the liver's bile drainage system?

It produces bile in the liver.

It connects the gall bladder with the portal vein.

It stores bile from the liver.

It transports bile directly to the small intestine. (correct)

In which zone of the acinus is ischaemic/toxic injury most severe?

Zone 2

Zone 3 (correct)

Zone 1

All zones are equally affected

What structures are included in the smallest branches of the portal tracts?

Hepatic veins and bile ducts

Central vein and bile acids

Portal vein, hepatic artery, and bile duct (correct)

Hepatic artery and hepatic veins

Which statement correctly describes the function of canaliculi in the liver?

They facilitate the secretion of bile from hepatocytes. Signup and view all the answers

What is the acinus in liver histology?

A functional unit of hepatocytes and sinusoids from adjacent lobules supplied by one portal tract. Signup and view all the answers

What characterizes bridging fibrosis in liver damage?

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

Which of the following is NOT a characteristic of cirrhosis?

Increased liver functionality Signup and view all the answers

What is the term for chronic passive venous congestion of the liver characterized by a specific gross appearance?

Nutmeg liver Signup and view all the answers

What is the primary consequence of portal hypertension in cirrhosis?

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

What are the consequences of extensive acute liver damage?

Acute liver failure may occur Signup and view all the answers

What type of inflammatory cell is predominant in liver disease?

Lymphocytes, depending on the aetiology Signup and view all the answers

In the context of liver biopsy, what do grading systems assess?

Grade and stage of liver damage independently Signup and view all the answers

In which condition is there an obstruction to venous outflow from the liver?

Budd Chiari syndrome Signup and view all the answers

Which of the following is NOT a liver function?

Production of insulin Signup and view all the answers

What change occurs in sinusoids due to cirrhosis?

Loss of fenestrations in sinusoids Signup and view all the answers

Which factor causes splanchnic vasodilatation in portal hypertension?

Increased nitric oxide (NO) levels Signup and view all the answers

What defines chronic liver disease according to duration?

More than 6 months Signup and view all the answers

What is an essential visual characteristic of liver cirrhosis when using a trichrome stain?

Fibrous tissue appears blue separating regenerative nodules Signup and view all the answers

Which type of liver injury is characterized by massive hepatic necrosis?

Irreversible cell death Signup and view all the answers

What is the likely outcome with ongoing liver insult leading to chronic damage?

Development of fibrosis and potential cirrhosis Signup and view all the answers

Which liver enzymes are usually elevated in ischaemic liver injury?

ALT and AST Signup and view all the answers

What primarily leads to increased pressure in the portal venous system?

Increased blood flow to the intestines Signup and view all the answers

What is a common consequence of portal hypertension in relation to fluid retention?

Leakage of fluid from peritoneal vessels Signup and view all the answers

Which of the following best describes compensated cirrhosis?

May be an unstable state despite absence of symptoms Signup and view all the answers

What role does the renin-angiotensin-aldosterone system play in response to portal hypertension?

Stimulates sodium and water retention Signup and view all the answers

What effect do porto-systemic shunts have on liver function?

By-pass liver, reducing its function Signup and view all the answers

What is a potential trigger for decompensating cirrhosis?

Surgical intervention Signup and view all the answers

Which condition may indicate decompensated liver cirrhosis?

Development of hepatic encephalopathy Signup and view all the answers

What characteristic is associated with ascites due to portal hypertension?

Preferential accumulation in the peritoneal cavity Signup and view all the answers

What is the approximate median survival time for a patient with compensated cirrhosis?

9 years Signup and view all the answers

Which factor significantly increases the 1-year mortality rate in patients with cirrhosis?

Presence of varices Signup and view all the answers

What is the median survival time for decompensated cirrhosis?

1.6 years Signup and view all the answers

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

Chronic hepatitis Signup and view all the answers

Which statement best summarizes the prognosis of patients with decompensated cirrhosis?

Their survival rates are consistently worse than those with compensated cirrhosis. Signup and view all the answers

What is the reported 1-year mortality rate for patients with decompensated cirrhosis presenting with ascites?

20% Signup and view all the answers

In terms of prognosis, how does the development of complications in cirrhosis affect mortality?

It sharply increases mortality. Signup and view all the answers

Which of the following conditions is associated with a highest mortality risk exceeding 50% in decompensated cirrhosis?

Other complications Signup and view all the answers

What outcome is likely if liver damage is extensive and leads to acute liver failure?

Permanent fibrosis Signup and view all the answers

Which type of cell injury is characterized by the death of small groups of liver cells?

Spotty necrosis Signup and view all the answers

Which condition involves obstruction to venous outflow from the liver, leading to liver injury?

Budd Chiari syndrome Signup and view all the answers

In chronic passive venous congestion of the liver, what is the characteristic gross appearance known as?

Nutmeg liver Signup and view all the answers

What typically marks the initial phase of ischaemic liver injury?

Marked elevation of liver tests Signup and view all the answers

What is a possible consequence of ongoing liver injury that results in chronic damage?

Development of cirrhosis Signup and view all the answers

Which of the following provides the liver with its primary blood supply?

Hepatic artery Signup and view all the answers

Which statement best describes ischaemic hepatitis?

Results from hypoperfusion and circulatory failure Signup and view all the answers

What characteristic feature is shared by both compensated and decompensated cirrhosis?

Presence of varices Signup and view all the answers

What is a primary consequence of chronic biliary disease on liver function?

Retention of bile salts Signup and view all the answers

What characterizes the inflammation assessment of liver damage?

Extent of necrosis and inflammation type Signup and view all the answers

Which of the following conditions is most likely to cause portal hypertension?

Chronic biliary obstruction Signup and view all the answers

How does ascites develop in the context of liver disease?

Increased portal venous pressure Signup and view all the answers

What cellular changes occur in the liver during prolonged injury?

Formation of collagen fibrosis Signup and view all the answers

Which of the following metabolic dysfunctions is frequently associated with non-alcoholic fatty liver disease?

Metabolic syndrome Signup and view all the answers

What important role do hepatic stellate cells play in liver pathology?

Collagen production during fibrosis Signup and view all the answers

What histological feature is indicative of cirrhosis as observed under H&E staining?

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

Which of the following best describes the changes in hepatic venous pressure gradient (HVPG) associated with cirrhosis?

HVPG rises as a result of increased resistance to blood flow Signup and view all the answers

In which specific pattern does portal fibrosis typically manifest in cases of alcohol-related liver disease?

Perivenular/perisinusoidal pattern Signup and view all the answers

What is a physiological consequence of portal hypertension resulting from cirrhosis?

Hyperdynamic circulation due to compensatory mechanisms Signup and view all the answers

Which of the following describes the stage of liver damage characterized by bridging fibrosis?

Fibrosis linking portal tracts and central veins Signup and view all the answers

What is a critical risk factor associated with cirrhosis that significantly impacts patient survival?

Presence of ascites Signup and view all the answers

What vascular alteration is associated with advanced cirrhosis?

Developing extensive collateral venous systems Signup and view all the answers

What histological staining technique is commonly used to visualize fibrous tissue in liver biopsy samples?

Trichrome stain Signup and view all the answers

What is the approximate median survival time for a patient with decompensated cirrhosis?

1.6 years Signup and view all the answers

Which complication is most likely to occur with decompensated cirrhosis?

Variceal hemorrhage Signup and view all the answers

What is the 1-year mortality rate for a patient with compensated cirrhosis with varices?

4% Signup and view all the answers

How does the presence of ascites affect the prognosis of a patient with cirrhosis?

It raises the 1-year mortality rate to 20% Signup and view all the answers

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

9 years Signup and view all the answers

In terms of prognosis, what is indicated by the development of other complications in decompensated cirrhosis?

Significantly high mortality risk Signup and view all the answers

What effect does compensated cirrhosis have on a patient's 1-year mortality rate?

Negligible; about 1% Signup and view all the answers

Which of the following statements regarding the prognosis of decompensated cirrhosis is accurate?

Median survival is approximately 1.6 years Signup and view all the answers

What physiological change leads to higher mean hydrostatic pressure in portal hypertension?

Increased portal blood flow Signup and view all the answers

Which of the following is a consequence of sodium and water retention associated with portal hypertension?

Decreased oncotic pressure Signup and view all the answers

Which mechanism describes the body's response to counteract widespread vasodilatation in portal hypertension?

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

What condition can lead to further reduction in liver perfusion and worsened liver damage in portal hypertension?

Formation of portal-systemic shunts Signup and view all the answers

How is ascites primarily caused in patients with portal hypertension?

Leakage from peritoneal vessels due to high hydrostatic pressure Signup and view all the answers

Which complication is commonly associated with decompensated cirrhosis?

Hepatic encephalopathy Signup and view all the answers

What is a primary effect of reflex renal vasoconstriction in the context of portal hypertension?

Decreased glomerular filtration rate Signup and view all the answers

Which factor could trigger decompensation in a compensated cirrhosis state?

Alcohol consumption Signup and view all the answers

Study Notes

Liver Structure

The liver is made up of plates of hepatocytes.
Sinusoids are located between the plates of hepatocytes.
Sinusoids drain into central hepatic vein branches.
Portal tracts consist of the smallest branches of the:
- Portal vein
- Hepatic artery
- Bile duct
There is a sharp interface between the portal tract and the surrounding parenchyma.

Bile Drainage

Bile is formed by hepatocytes.
Bile is secreted into canaliculi between hepatocytes.
Small ductules form from canaliculi, which join to form small ducts in portal tracts.
The left and right hepatic ducts join to form the common hepatic duct.
The common hepatic duct joins the cystic duct to form the common bile duct.
75% of the time, the common bile duct and pancreatic duct join at the ampulla.
The gallbladder is only responsible for bile storage.

Acinus

The acinus is the favoured concept for understanding liver structure.
The center of the acinus is the portal tract, which serves as the focal point for blood supply.
The acinus refers to the hepatocytes and sinusoids from two adjacent lobules supplied by one portal tract.
This concept helps explain patterns of damage: ischemic/toxic injury is most severe in zone 3.

Vascular Injury to the Liver

Chronic (passive) venous congestion of the liver is associated with right heart failure (e.g., cor pulmonale, mitral stenosis).
- It is most marked in rare cases of tricuspid incompetence and constrictive pericarditis.
- Mild elevation of liver blood tests (ALT, AST) is common.
Obstruction to venous outflow from the liver (hepatic vein/IVC) is known as Budd-Chiari syndrome.
Infarction of the liver is extremely unusual.
Ischemic injury to the liver ("ischemic hepatitis," "shock liver") is associated with hypoperfusion, hypotension/shock/circulatory failure.
- Marked elevation of liver blood tests (ALT, AST) is seen.
- Outcome depends on the underlying cause.
- Susceptibility is increased by passive venous congestion or cirrhosis.

Liver Function

Synthesis of most plasma proteins, including clotting factors.
Bile formation:
- Bilirubin excretion.
- Bile salts for digestion of fats and fat-soluble vitamins (ADEK).
Detoxification of endogenous and exogenous compounds.
Intermediary metabolism (alteration and storage).
Immune function, acting as a buffer between the gut and the rest of the body.
Storage of normal and abnormal substances.
Hematopoiesis (in fetal and infant stages).

Damage to the Liver

The liver has reserve and regenerative capacity.
Outcomes of acute damage depend on:
- The degree of damage.
- The risk of acute liver failure if damage is extensive.
- Recovery with transient damage and no acute liver failure.
- Chronic damage if the insult is ongoing or repeated.
Chronic liver disease is defined as lasting more than 6 months.
Ongoing insult leads to chronic disease, characterized by:
- Fibrosis, increasing in degree with progression to cirrhosis.
Different causes may co-exist, be superimposed, or potentiate each other.

Patterns of Cell Damage/Death

Different types of cell injury can be reversible or irreversible.
Different triggers for injury:
- Direct cytopathic, cytotoxic, or ischemic effects.
- Damage to hepatocytes rendering them antigenic (e.g., HBV).
- Damage to cells perceived as antigenic (e.g., autoimmune hepatitis).
Different degrees of injury:
- Single cell death (apoptosis).
- Small groups of cells die (spotty necrosis).
- Large, confluent groups of cells die (bridging necrosis).
- Massive hepatic necrosis.

Assessment of Liver Damage

Inflammation +/- necrosis: extent is "grade."
Inflammation can be portal/periportal or lobular (parenchymal).
Interface inflammation is known as "piecemeal necrosis."
Necrosis can be present in single cells, as spotty necrosis, or bridging necrosis.
Predominant inflammatory cell type depends on the etiology, not the duration of the disease.

Fibrosis

Degree/extent of fibrosis is "stage."
Fibrosis can be portal, periportal, bridging, or cirrhosis.
Portal fibrosis connects portal tracts to each other.
Periportal fibrosis connects portal tracts to central veins.
Bridging fibrosis connects portal tracts to portal tracts or portal tracts to central veins.
Cirrhosis is the most advanced stage of fibrosis.

Stages of Liver Fibrosis

  - Stages of liver fibrosis are assessed using a trichrome stain. 
  - Fibrous tissue is stained blue by the trichrome stain.

Definition of Cirrhosis

Cirrhosis is a diffuse distortion of the liver architecture with:
- Fibrous bands/septa surrounded by regenerative nodules.
- Distorted vascular relationships.
Cirrhosis causes portal hypertension.
It reduces the functional capacity of the liver.
There is an increased risk of hepatocellular carcinoma in cirrhosis.

Cirrhosis (Continued)

Cirrhosis is a structural endpoint of chronic liver disease due to ongoing damage.
It represents a state of diminished liver reserve.
Vascular changes due to cirrhosis include:
- Obliteration/thrombosis of veins within the liver.
- Collateral channels/shunts forming within the liver.
- Sinusoids becoming "capillarized" (loss of fenestrations).
- Rising hepatic venous pressure gradient (HVPG).

Portal Hypertension in Cirrhosis

Initiated by increased hepatic resistance to portal blood flow, leading to elevated HVPG.
Augmented by splanchnic vasodilatation (via.NO), increasing portal blood flow.
Splanchnic vasodilatation lowers total peripheral resistance (TPR) and blood pressure (BP).
A compensatory increase in cardiac output leads to a hyperdynamic circulation in cirrhosis.
Splanchnic vasodilatation triggers compensatory mechanisms.

Simplified View of Portal Hypertension

Increased blood supply to the intestines (splanchnic vasodilatation) leads to increased blood flow in the portal system.
With a blocked liver, the portal venous system experiences increased pressure.

Portal Hypertension, Ascites & HRS

Compensatory mechanisms for widespread vasodilatation include:
- Activation of the renin-angiotensin-aldosterone system.
- Stimulation of ADH secretion.
- Sodium and water retention.
- Reflex renal vasoconstriction, reducing perfusion and glomerular filtration rate (GFR).
Ascites develops due to:
- Sodium and water retention associated with portal hypertension.
- Preferential accumulation of fluid in the peritoneal cavity.
- Leakage from peritoneal vessels.
- Higher mean hydrostatic pressure due to portal hypertension.
- Lower oncotic pressure (due to low albumin).

Portal Hypertension & Shunts

Shunts develop to attempt to decompress portal hypertension:
- Intrahepatic porto-systemic shunts/collaterals.
- Extrahepatic porto-systemic anastomoses dilate.
- Therapeutic insertion of transjugular intrahepatic porto-systemic shunt (TIPS).
Shunted blood bypasses the liver:
- Further reduces liver function (increases risk of hepatic encephalopathy).
- Exacerbated by "capillarisation" of sinusoids.
- Reduces liver perfusion, worsening 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 esophagogastroduodenoscopy (OGD).
Potentially unstable state:
- Further injury may trigger decompensation:
  - Infection, bleeding, hypotension, alcohol, medications, dehydration, trauma, surgery.

Decompensated Cirrhosis

Decompensated cirrhosis is characterized by:
- Ascites (may become refractory to treatment).
- Hepatic encephalopathy.
- Variceal hemorrhage.
- Hepatorenal syndrome (HRS).
- Jaundice.
- Infection (esp. spontaneous bacterial peritonitis).
- Hepatocellular carcinoma.

Prognosis of Cirrhosis

Decompensation significantly affects prognosis (rate of progression).
Prognosis is poor:
- One-year mortality is 1% for compensated cirrhosis.
- One-year mortality is 4% for compensated cirrhosis with varices.
- One-year mortality is 20% for decompensated cirrhosis with ascites.
- One-year mortality is >50% for decompensated cirrhosis with other features.

Natural History of Chronic Liver Disease

Development of compensated cirrhosis can progress to decompensated cirrhosis, leading to death.
Median survival is approximately 9 years for patients with compensated cirrhosis.
Median survival is approximately 1.6 years for patients with decompensated cirrhosis.
Orthotopic Liver Transplant (OLT) represents a treatment option.

Survival Times in Cirrhosis

Survival times in cirrhosis are influenced by the stage of the disease.
Median survival for all patients with cirrhosis is approximately 9 years.
Median survival for patients with decompensated cirrhosis is approximately 1.6 years.

Overview of Liver Disease

Liver disease is a significant cause of morbidity and mortality globally.
Liver disease is less common than heart disease, cancer, and stroke.
Gastroenterologists manage liver disease, sometimes specialising as hepatologists.
Surgeons manage gallstones, pancreatitis, and extrahepatic biliary tract disease.
GPs manage abnormal liver blood tests.
Common aetiologies are:
- Cirrhosis: alcohol versus chronic viral disease (HBV)
- Tumours: liver metastases and pancreatic cancer versus primary hepatocellular carcinoma
- Disease patterns vary depending on the geographical location.

Causes of Liver Damage

Liver damage can be caused by a variety of factors including:
- Alcohol abuse
- Non-alcoholic fatty liver disease (NAFLD)
  - Associated with metabolic syndrome (type 2 DM, obesity etc.).
- Viruses:
  - Acute infections: Hep A, E
  - Chronic infections: Hep B, C
- Drugs
- Autoimmune diseases
- Inherited metabolic disorders: HFE, Wilson's disease, A1AT deficiency
- Vascular disorders: congestion or ischemia
- Chronic biliary disease: injury to the liver due to retained bile salts