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What characterizes acute liver failure in a patient with a previously normal liver?
Which of the following is a common cause of acute liver failure in the UK?
What is a potential histological finding in cases of acute liver failure?
Which of the following conditions is NOT classified as a cause of acute liver failure?
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What does portal hypertension commonly lead to in patients with liver disease?
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Which clinical feature is characteristic of acute liver failure?
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What causes renal impairment in hepatorenal syndrome?
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Which stage of hepatic encephalopathy involves coma?
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Which statement about hepatic encephalopathy is true?
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Which treatment approach is appropriate for hepatic encephalopathy?
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What is a potential consequence of increased glutamine in the brain associated with hepatic encephalopathy?
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Which stage of hepatic encephalopathy is characterized by minimal symptoms that may affect social functions?
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What is the primary mechanism by which ammonia is detoxified in the brain during liver dysfunction?
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What is the main indication for treating ascitic fluid in patients with a suspected infection?
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Which liver enzyme is the most sensitive and specific marker for hepatocellular damage?
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What does an AST/ALT ratio greater than 2 usually indicate?
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Which laboratory test is least indicative of acute liver damage?
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Which test correlates with elevated alkaline phosphatase to demonstrate liver origin?
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Why might ALT levels be normal in a patient with chronic liver disease?
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Which of the following could indicate an extrahepatic source of AST?
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What is the main source of alkaline phosphatase (ALP) in the liver?
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What is the primary mechanism leading to ascites in liver disease?
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What is the commonest cause of portal hypertension?
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Which treatment is considered for primary prevention of variceal bleeding?
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What laboratory finding is important for diagnosing spontaneous bacterial peritonitis (SBP)?
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What is the effect of lactulose in the treatment of hepatic encephalopathy?
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What condition is characterized by periumbilical collateral veins as a result of portal hypertension?
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Which of the following is a common symptom associated with ascites?
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Which of the following is considered a contraindication for diuretic use in the management of ascites?
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What is the primary goal of treating variceal bleeding?
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What is the recommended approach for managing diuretic-resistant ascites?
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Which of the following conditions can lead to acute liver failure through pregnancy-related mechanisms?
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Which laboratory marker is critical for diagnosing acute liver failure in previously healthy patients?
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Which viral pathogen among the following is primarily associated with acute liver failure?
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Which of the following describes a histological finding consistent with acute liver failure?
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What is one potential consequence of severe cholestasis related to liver failure?
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What is a key characteristic of hepatorenal syndrome?
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Which of the following stages of hepatic encephalopathy is characterized by drowsiness?
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Which factor is NOT considered a precipitating cause of hepatic encephalopathy?
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What is the physiological consequence of increased ammonia in the brain?
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Which classification of hepatic encephalopathy is associated with decompensated liver cirrhosis?
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What is the most significant complication associated with severe hepatic encephalopathy?
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What distinguishes minimal hepatic encephalopathy from overt hepatic encephalopathy?
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Why is hepatorenal syndrome often diagnosed as a diagnosis of exclusion?
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What is a significant indicator for initiating treatment in suspected spontaneous bacterial peritonitis (SBP)?
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Which enzyme is known to leak from hepatocytes due to hepatocellular damage?
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In which situation is an AST/ALT ratio greater than 5 most indicative?
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Which lab test is best correlated with liver obstruction or cholestasis?
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What does a high alkaline phosphatase (ALP) level indicate?
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What could be a reason for normal AST and ALT levels in a patient with chronic liver disease?
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What is the typical AST/ALT ratio in patients with alcoholic hepatitis?
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Which of the following tests evaluates the liver's synthetic function?
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What is a common complication associated with ascites due to liver disease?
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What is a therapeutic approach for managing refractory ascites in patients with cirrhosis?
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Which of the following is NOT a mechanism contributing to ascites development in liver disease?
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What is the primary prevention method aimed at reducing the risk of variceal bleeding?
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Which type of portal hypertension is characterized by increased resistance to portal blood flow?
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What is the most common cause of ascites?
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What is the recommended action if a variceal bleed does not respond to initial treatments?
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Which finding is indicative of portal hypertension during physical examination?
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What is the significance of using rifaximin in the management of hepatic encephalopathy?
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Which of the following conditions is classified under hepatic causes of portal hypertension?
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Study Notes
Acute Liver Failure
- Acute liver injury with encephalopathy and deranged coagulation (INR > 1.5) in a patient with a previously normal liver
- Rare but life-threatening syndrome
- Most common causes vary worldwide, but usually involve viral hepatitis (especially in the UK, paracetamol overdose is common)
- Histologically, there is necrosis of liver acini, involving a substantial part of the liver
- Severe fatty change may be seen in some cases, examples include pregnancy, Reye syndrome, or after intravenous tetracycline
Causes of Acute Hepatic Failure
- Viral hepatitis (e.g., Hepatitis A, Hepatitis B, cytomegalovirus, hemorrhagic fever virus)
- Drugs (e.g., paracetamol, antibiotics, antidepressants, salicylate [Reye syndrome], NSAID, herbal medicines)
- Toxins, organic solvents, mushroom toxin
- Hepatic failure in pregnancy (e.g., acute fatty liver of pregnancy, HELLP syndrome)
- Vascular causes (e.g., Budd-Chiari syndrome, portal vein thrombosis)
- Alpha-1 antitrypsin deficiency
- Wilson disease
- Malignancy (e.g., extensive metastases)
- Heatstroke
Clinical Features of Acute Liver Failure
- Jaundice
- Hepatic encephalopathy
- Fever, vomiting, low blood pressure, low blood glucose
- Cerebral edema (in 80% of patients)
- Impaired gluconeogenesis
- Kidney injury (e.g., hepatorenal syndrome and acute tubular necrosis)
Hepatorenal Syndrome
- Renal impairment secondary to liver disease
- Haemodynamic effects of portal hypertension reduce renal perfusion, typically associated with ascites
- Diagnosis of exclusion – no other kidney pathology
- Poor prognosis
Hepatic Encephalopathy
- Spectrum of neuro-psychiatric abnormalities seen in liver dysfunction and/or porto-systemic shunting
- Functional disturbance of the brain, potentially reversible
- If severe, associated with cerebral edema and cerebral hypoperfusion
- Types:
- Type A: acute liver failure
- Type B: porto-systemic shunting with normal liver
- Type C: cirrhosis (= decompensation)
- Episodic (may be recurrent) HE +/- persistent HE
Stages of Hepatic Encephalopathy
- Stages 1-4: Confusion, Drowsiness, Somnolence, Coma
- Minimal HE may be revealed by psychometric testing
- Minimal HE can affect social function, work life, behavior, and fitness to drive
- Minimal HE + stage 1 HE = covert HE, stages 2 to 4 = overt HE
Hepatic Encephalopathy: Pathogenesis
- Reduced detoxification in the liver
- Portosystemic shunting allows more ammonia to enter the systemic circulation, bypassing the liver
- Detoxification of ammonia occurs more in skeletal muscle/kidney and converted to glutamate (NOT UREA as in the liver)
- Astrocytes in the brain also detoxify ammonia via glutamine synthetase
- Increased glutamine in the brain brings more water into astrocytes → swelling of astrocytes → cerebral edema & intracranial hypertension
Hepatic Encephalopathy: Treatment
- Identify and correct precipitating factors (e.g., infection, bleeding, dehydration, drugs)
- Reduce ammonia production and absorption (e.g., lactulose [oral or enema], non-absorbable antibiotics [e.g., rifaximin], fluids, stop diuretic therapy)
Portal Hypertension
- Classified by level/site of origin of portal hypertension
- Commonest cause is cirrhosis
- Pathogenesis in cirrhosis:
- Initiated: increased resistance to portal blood flow
- Augmented: increased portal blood flow
- Classification of causes of portal hypertension:
- Pre-hepatic: portal vein thrombosis
- Hepatic:
- Cirrhosis
- Non-cirrhotic (e.g., portal tract fibrosis due to schistosomiasis)
- Post-hepatic: obstruction of venous outflow from the liver (rare)
Consequences of Portal Hypertension
- Porto-systemic collaterals:
- Extrahepatic: portal venous and systemic venous circulations anastomose:
- Varices (esophageal and gastric, risk of bleed)
- Rectal, periumbilical (‘caput medusae’)
- Extrahepatic: portal venous and systemic venous circulations anastomose:
- Shunting of portal venous blood (reduced liver function)
- Haemodynamic alterations:
- Ascites and hepatorenal syndrome
- Splenomegaly (congestive)
- Secondary hypersplenism
Esophageal and Gastric Varices
- 30% of patients with esophageal varices will have a bleed
- Mortality is high, high rate of recurrence
- Heavy alcohol users are at increased risk
- Remember: not all upper GI bleeds are varices
Esophageal and Gastric Varices: Prevention and Treatment
- Primary Prevention: Screen to identify and treat moderate to severe varices before a first bleed, endoscopic band ligation and/or non-selective beta blockers.
- Secondary Prevention: Treat to prevent recurrent bleeding, endoscopic band ligation and/or non-selective beta blockers.
- Variceal Bleed: Resuscitate, drugs to reduce portal blood flow, prevent/treat complications (aspiration, infection, HE), endoscopic treatment of varices by band ligation, endoscopic sclerotherapy not favoured (complications), if above fail: TIPS placement or surgery.
Ascites in Liver Disease
- Sodium retention by the kidneys → increases the volume of extracellular fluid → ascites and edema
- Increased hydrostatic pressure due to portal hypertension
- Lower oncotic pressure (to keep fluid in) due to low albumin
- Clinical Presentation:
- Abdominal distension
- Shifting dullness on percussion
Ascites
- Cirrhosis is the commonest cause (>80%)
- Other causes: malignancy, non-cirrhotic portal hypertension, heart failure, pancreatitis, TB
Ascites Management
- Paracentesis = tap of ascites fluid
- Diagnostic tap – do cell count, microbiology (blood culture bottles), albumin, cytology
- Therapeutic tap - diuretic-resistant ascites in cirrhosis
- Treatment:
- Na+ restriction, diuretics (spironolactone)
- Avoid NSAID (risk of acute renal failure and hyponatremia, lowers effect of diuretics)
- High index of suspicion for infection (low threshold for paracentesis)
- Diuretic-resistant = refractory ascites
Spontaneous Bacterial Peritonitis (SBP)
- Infection of ascites fluid without evidence of surgically-treatable intra-abdominal cause
- Infection associated with cirrhosis (E.coli, Klebsiella)
- Early diagnosis and prompt treatment give better outcome
- Subtle/silent presentation
- Low threshold for paracentesis of ascites fluid
- Suspect: Fever, abdominal pain/tenderness, altered mental state
- Treat if ascites fluid cell count >250 polys/mm3
- Antibiotic prophylaxis if high risk (e.g., previous SBP or bleed)
Liver Blood Tests
-
Hepatocellular Damage:
- Transaminases (ALT, AST)
-
Obstruction to Bile Flow (Cholestasis):
- Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT)
- Bilirubin
-
Liver Function:
- Bilirubin – abnormality not liver or biliary tract specific
- Albumin (long half life, indicator of chronic damage)
- Coagulation function (PT/INR) (clotting factors have short half life– better indicator of acute damage)
Hepatocellular Damage: Liver Enzymes
- Alanine transaminase (ALT): sensitive/specific marker for hepatocellular damage
- Aspartate transaminase (AST): less specific, also in muscle, myocardium, kidney
- Both leak from damaged hepatocytes
- Level of rise is poorly correlated with severity/prognosis
- Very high in acute hepatocellular damage
- May be only mildly elevated or normal despite chronic liver disease
- AST/ALT ratio can be informative
- Usually >2 suggests alcohol-related damage
AST/ALT Ratio
- Ratio of AST to ALT made by hepatocytes is approximately 2.5:1. AST is removed from serum by the liver sinusoidal cells twice as quickly, so resulting serum levels are about equal in healthy individuals.
- BUT in conditions with chronic, constant hepatocyte damage (e.g., alcoholic hepatitis, hepatocellular carcinoma) and during early-stage acute liver damage (e.g. viral hepatitis) the serum levels of AST and ALT reflect levels closer to background in hepatocytes.
- An AST/ALT ratio >5 indicates an extrahepatic source of AST.
Obstructive (Cholestatic) Liver Enzymes
-
Alkaline Phosphatase (ALP):
- Situated on the hepatocyte border of bile canaliculi
- Hepatocytes react to obstruction to bile flow by leaking alkaline phosphatase
- Other sources: bone, placenta
-
Gamma-glutamyl transferase (GGT):
- Very sensitive but not specific
- Good for correlating with elevated alkaline phosphatase to demonstrate that ALP is of liver origin
- Also induced by alcohol, drugs.
Acute Liver Failure
- Acute liver failure is a rare but life-threatening syndrome characterized by encephalopathy and impaired coagulation (INR > 1.5) in a patient with a previously normal liver.
- The most common causes of acute liver failure vary globally, but often involve viral hepatitis or paracetamol overdose.
- Histologically, acute liver failure is characterized by necrosis of liver cell clusters (acini) affecting a significant portion of the liver.
- Severe fatty changes in the liver can be observed in cases of pregnancy, Reye syndrome, or after intravenous tetracycline use.
Causes of Acute Hepatic Failure
- Viral: hepatitis A, hepatitis B, cytomegalovirus, hemorrhagic fever viruses
- Drugs: paracetamol, antibiotics, antidepressants, salicylates (Reye syndrome), NSAIDs, herbal medicines
- Toxins & Solvents: organic solvents, mushroom toxin
- Pregnancy: acute fatty liver of pregnancy, HELLP syndrome
- Vascular: Budd-Chiari syndrome, portal vein thrombosis
- Genetic: alpha-1 antitrypsin deficiency, Wilson disease
- Malignancy: extensive metastases
- Heatstroke
Clinical Features of Acute Liver Failure
- Jaundice
- Hepatic encephalopathy
- Fever, vomiting, low blood pressure, low blood glucose
- Cerebral edema (80% of patients)
- Impaired gluconeogenesis
- Kidney injury (hepatorenal syndrome)
- Acute tubular necrosis
Hepatorenal Syndrome
- Renal impairment secondary to liver disease.
- Haemodynamic effects of portal hypertension impair renal perfusion, often associated with ascites.
- Diagnosis of exclusion - other kidney pathologies are ruled out such as:
- Hypovolemia/shock
- Acute tubular necrosis
- Associated with a poor prognosis.
Hepatic Encephalopathy
- Spectrum of neuro-psychiatric abnormalities seen in liver dysfunction and/or porto-systemic shunting.
- Represents a functional disturbance of the brain, potentially reversible.
- Severe cases can lead to cerebral edema and cerebral hypoperfusion.
- Classified into four types:
- Type A: acute liver failure
- Type B: porto-systemic shunting with a normal liver
- Type C: cirrhosis (decompensation)
- Episodic (may be recurrent) HE +/- persistent HE
Stages of Hepatic Encephalopathy
- Stage 1: Confusion
- Stage 2: Drowsiness
- Stage 3: Somnolence
- Stage 4: Coma
Hepatic Encephalopathy: Pathogenesis
- Reduced detoxification in the liver.
- Portosystemic shunting allows ammonia to enter the systemic circulation, bypassing the liver.
- Ammonia detoxification shifts from the liver to skeletal muscle and kidney, leading to the conversion of ammonia to glutamate.
- Astrocytes in the brain detoxify ammonia via glutamine synthetase.
- Increased glutamine in the brain causes water influx into astrocytes, leading to brain swelling, cerebral edema, and intracranial hypertension.
Hepatic Encephalopathy: Treatment
- Identify and correct precipitating factors:
- Infection
- Bleeding
- Dehydration
- Drug use (sedatives, alcohol)
- Reduce ammonia production and absorption:
- Lactulose (oral or enema): acidifies the gut
- Non-absorbable antibiotics (e.g., Rifaximin): reduce urease-producing bacteria
- Fluids: prevent dehydration
- Discontinue diuretic therapy
Portal Hypertension
- Classified by the level/site of origin of portal hypertension.
- The most common cause is cirrhosis.
- Pathogenesis in cirrhosis:
- Increased resistance to portal blood flow
- Increased portal blood flow
- Classification of causes of portal hypertension:
- Pre-hepatic: portal vein thrombosis
-
Hepatic:
- Cirrhosis
- Non-cirrhotic (e.g., portal tract fibrosis due to schistosomiasis)
- Post-hepatic: obstruction of venous outflow from the liver (rare)
Consequences of Portal Hypertension
-
Porto-systemic collaterals:
- Extrahepatic anastomoses between portal venous and systemic venous circulations:
- Varices (esophageal and gastric, risk of bleeding)
- Rectal varices
- Periumbilical varices (“caput medusae”)
- Extrahepatic anastomoses between portal venous and systemic venous circulations:
- Shunting of portal venous blood: reduced liver function
-
Haemodynamic alterations:
- Ascites and hepatorenal syndrome
- Splenomegaly: congestive, secondary hypersplenism
Esophageal and Gastric Varices
- 30% of patients with esophageal varices will experience a bleed, which carries a high mortality rate and recurrence risk.
- Heavy alcohol users are particularly susceptible.
Esophageal and Gastric Varices: Management
-
Primary prevention:
- Screen for and treat moderate to severe varices before their first bleed.
- Endoscopic band ligation and/or non-selective beta blockers.
-
Secondary prevention:
- Treatment to prevent recurrent bleeding.
- Endoscopic band ligation and/or non-selective beta blockers.
-
Variceal bleed:
- Resuscitate the patient.
- Medications to reduce portal blood flow.
- Prevent/treat complications (aspiration, infection, HE).
- Endoscopic treatment of varices by band ligation.
- Placement of a Transjugular Intrahepatic Portosystemic Shunt (TIPS) or surgery if other methods fail.
Ascites in Liver Disease
- Ascites results from increased fluid volume in the extracellular space due to:
- Sodium retention by the kidneys
- Increased hydrostatic pressure due to portal hypertension
- Reduced oncotic pressure (albumin levels)
- Clinical presentation: abdominal distention, shifting dullness on percussion.
Ascites
- Cirrhosis is the most common cause (>80%).
- Other causes:
- Malignancy
- Non-cirrhotic portal hypertension
- Heart failure, pancreatitis, tuberculosis
Ascites: Management
-
Paracentesis:
- Diagnostic: analyze ascites fluid for cell count, microbiology, albumin, and cytology.
- Therapeutic: for diuretic-resistant ascites in cirrhosis.
-
Medical management:
- Sodium restriction
- Diuretics (spironolactone)
- Avoid NSAIDs
- High index of suspicion for infection
- Diuretic-resistant ascites = refractory ascites
Spontaneous Bacterial Peritonitis (SBP)
- Infection of ascitic fluid without surgically-treatable causes.
- Most commonly associated with cirrhosis (E.coli, Klebsiella).
- Early diagnosis and treatment lead to better outcomes.
- Often presents subtly or silently.
- A low threshold for paracentesis should be used.
- Suspect SBP with: fever, abdominal pain/tenderness, altered mental state.
- Treat if ascitic polymorphonuclear cell count > 250 cells/mm3.
- Implement antibiotic prophylaxis for high-risk individuals (e.g., previous SBP or bleed).
Liver Blood Tests
-
Hepatocellular damage:
- Transaminases (ALT, AST)
-
Obstruction to bile flow (cholestasis):
- Alkaline phosphatase (ALP) , Gamma-glutamyl transferase (GGT)
- Bilirubin
-
Liver function:
- Bilirubin
- Albumin
- Coagulation function (PT/INR)
Hepatocellular Damage: Liver Enzymes
- Alanine transaminase (ALT): sensitive and specific marker for hepatocellular damage.
- Aspartate transaminase (AST): less specific, also present in muscle, myocardium, and kidney.
- Both enzymes leak from damaged hepatocytes.
- The level of enzyme elevation does not correlate well with severity or prognosis.
- AST and ALT are very high in acute hepatocellular damage.
- They may be mildly elevated or normal despite chronic liver disease.
AST/ALT Ratio
- In healthy individuals, the AST/ALT ratio is approximately 2.5:1.
- In conditions with chronic or recent hepatocyte damage (e.g., alcoholic hepatitis, hepatocellular carcinoma), the AST/ALT ratio may be closer to 1.
- An AST/ALT ratio >5 suggests an extrahepatic source of AST.
Obstructive (Cholestatic) Liver Enzymes
-
Alkaline phosphatase (ALP):
- Present on the border of bile canaliculi in hepatocytes.
- Elevation indicates obstruction to bile flow.
- Other sources: bone, placenta
-
Gamma-glutamyl transferase (GGT):
- Very sensitive but not specific.
- Helps confirm that elevated ALP is of liver origin.
- Also induced by alcohol and drugs.
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Description
This quiz explores the critical aspects of acute liver failure, focusing on its causes, symptoms, and histological features. It emphasizes the importance of recognizing this rare but life-threatening condition, especially in relation to viral hepatitis and drug overdoses. Test your knowledge and understanding of this significant medical syndrome.
