Liver Disorders and Functions Quiz

Liver Disorders

• The liver is a vital organ with four lobes and hepatic lobules.
• Its primary blood sources are the hepatic artery and hepatic portal vein.
• Bile is collected by bile canaliculi and transported via the common hepatic duct.

Functions of Liver

• Metabolism of carbs, lipids, and proteins, including breakdown of red blood cells (reticuloendothelial system).
• Detoxification of endogenous and exogenous compounds.
• Bilirubin metabolism.
• Protein synthesis (e.g., albumin, acute-phase proteins, coagulation factors).
• Storage of substances.

Liver and Carbohydrate Metabolism

• Carbohydrate metabolism is linked to blood glucose levels.
• Glucose levels are regulated by the liver, influenced by insulin, glycogen, glycogenolysis, and gluconeogenesis.

Liver and Lipid Metabolism

• Lipids are water-insoluble and transported as lipoproteins.
• The liver produces lipoproteins, metabolizes fatty acids (acetyl-CoA) and triglycerides (for energy), and converts carbohydrates and proteins into fats.
• Cholesterol is converted to bile, a continuous process involving water, bile salts, bilirubin, fatty acids, and cholesterol.

Liver and Protein Metabolism

• The liver produces plasma proteins and clotting factors.
• It deaminates amino acids, converting them to ammonia (a byproduct).
• The liver forms waste products (e.g., urea) from ammonia.

Liver and Bilirubin Metabolism

• Bilirubin results from hemoglobin degradation.
• Unconjugated bilirubin is converted to conjugated bilirubin using glucuronic acid.
• High levels of unconjugated bilirubin cause cell damage, jaundice, and brain toxicity.
• Total bilirubin is the sum of unconjugated and conjugated bilirubin.

Liver Tests (LFTs)

• Common LFT panels include Alanine aminotransferase (ALT), measuring hepatocyte integrity; Bilirubin; Alkaline phosphatase (ALP), abundant in bile canaliculi; and Albumin.

Aminotransferases

• Alanine aminotransferase (ALT) is a sensitive, non-specific marker of acute hepatocyte damage (hepatitis, toxic injury).
• Aspartate aminotransferase (AST) is produced by hepatocytes, skeletal muscles, kidney, brain, and heart, less specific for liver assessment.

Bilirubin

• Bilirubin is derived from heme (hemoglobin).
• Unconjugated bilirubin is excreted into bile, and conjugated bilirubin is degraded by intestinal bacteria to stercobilinogen.
• Small amounts of stercobilinogen are excreted in urine as urobilinogen.
• Elevated total bilirubin may indicate liver disease, hemolysis, or biliary obstruction.
• Elevated indirect bilirubin may point to hemolysis or liver dysfunction.
• Elevated direct bilirubin suggests liver disease or biliary obstruction.

Jaundice

• Jaundice is caused by excess bilirubin (>50 µmol/L).
• Its three main causes are hemolysis (pre-hepatic), failure of liver conjugation (hepatic), and biliary obstruction (post-hepatic).
• Increased indirect bilirubin in newborns may pose a risk of brain damage, necessitating phototherapy.

Alkaline Phosphatase (ALP)

• ALP is present in blood, derived from liver, bone, intestine, and placenta.
• Increased ALP in blood often signifies increased synthesis by cells lining bile canaliculi, cholestasis, or infiltrative liver diseases (like cirrhosis).

Plasma Proteins (Albumin)

• Albumin is produced by the liver with a 20-day biological half-life in plasma.
• Low albumin (hypoalbuminemia) can indicate advanced chronic liver disease or severe acute liver damage.

Prothrombin Time (PT)

• PT measures blood clotting time in seconds.
• It reflects hepatic synthesis function.
• Prothrombin, a liver-produced clotting protein, is activated by an enzymatic cascade.
• Its short half-life (60-72 hrs) makes PT a sensitive indicator of hepatic synthesis.
• Normal PT suggests adequate blood-clotting protein levels.

Gamma-Glutamyl Transpeptidase (GGT)

• GGT is a very sensitive marker of liver pathology, found in hepatocytes' endoplasmic reticulum.
• GGT is involved in detoxification and is widely distributed.
• Alcohol ingestion and drugs like phenytoin can increase GGT levels.
• GGT elevation is specifically associated with cholestasis.
• Increased GGT with normal ALT may suggest a non-liver-related cause for GGT elevation.

Acute Liver Disease

• Common causes include poisoning (paracetamol overdose, plant/fungal toxins), infections (hepatitis A, B, and C), and inadequate liver perfusion (blood loss).

Acute Liver Disease - Outcome

• Acute liver disease can resolve, progress to acute hepatic failure (medical emergency, potentially leading to chronic hepatic injury, increased blood ammonia), or lead to chronic hepatic damage.

Chronic Liver Disease

• Chronic liver damage involves gradual progression, leading to long-term liver injury.
• Conditions include alcoholic liver disease, chronic active hepatitis, primary biliary cirrhosis, and nonalcoholic fatty liver disease.

Cirrhosis

• Cirrhosis is the final stage of chronic liver damage with irreversible scarring, impaired function, and often associated with alcoholism.
• It may eventually progress to liver failure.
• Cirrhosis typically involves irreversible scarring and loss of liver function.

Diagnosis of Cirrhosis and Liver Failure

• Early cirrhosis may have no significant biochemical indicators.
• Late stages often present with jaundice, encephalopathy, ascites, and potentially bleeding, concluding eventually in terminal liver failure.
• Liver biopsy is the gold standard for diagnosis but not recommended with low platelet count or clotting factor issues.

Gilbert Syndrome

• Gilbert syndrome is a hereditary, autosomal recessive liver disease, characterized by a reduced activity of glucuronyl transferase.
• Affected individuals have decreased conjugation of bilirubin, resulting in high levels of unconjugated bilirubin.

Crigler-Najjar Syndrome

• Crigler-Najjar syndrome is a rare, autosomal recessive condition with no or severely reduced glucuronyl transferase activity leading to profound, life-threatening unconjugated bilirubinemia.
• Type I is typically life-threatening.
• Type II is treatable with phototherapy.

Dubin-Johnson Syndrome

• Dubin-Johnson syndrome is an autosomal recessive inherited disease characterized by a defect in bilirubin transport from the hepatocytes to the bile, resulting in conjugated bilirubinemia.
• This defect leads to the accumulation of bilirubin in the liver, causing dark pigmentation.
• Signs include jaundice, upper abdominal pain, anorexia, nausea, and vomiting, appearing generally in early adulthood.

Hepatitis

• Hepatitis is an inflammation of the liver with various causes, including viruses (A, B, C, D, and E), bacteria, toxic chemicals, drugs, and alcohol.
• Acute hepatitis typically resolves within six months, while chronic hepatitis lasts beyond six months.

Hepatitis A (HAV)

• HAV is a single-stranded RNA virus transmitted via the fecal-oral route.
• Individuals infected with HAV experience an incubation period before developing symptoms, which involve jaundice and feces that are a clay color.

Hepatitis B (HBV)

• HBV is a double-stranded DNA virus, transmitted through contact with blood, semen, or vaginal fluids.
• Incubation typically lasts 60-90 days.
• Signs include anorexia, vomiting, abdominal pain, dark urine, and jaundice.
• Some individuals progress to chronic liver disease.

Hepatitis C (HCV)

• HCV is a single-stranded RNA virus, transmitted through blood transfusions or contaminated needles.
• Symptoms may not appear for 2-26 weeks.
• Up to 70% of individuals lack initial symptoms.
• Most individuals with HCV progress to chronic conditions.

Laboratory Diagnosis of Viral Hepatitis

• Non-specific blood tests (bilirubin, liver enzymes: ALT, AST, ALP, and GGT) and specific blood tests to target viral antigens and antibodies (Anti-HAV IgM, HAV IgG, HBsAg, Anti-HBs, Anti-HBc, Anti-HBc IgM, Anti-HCV) determine and differentiate the type of hepatitis and its severity.

Hereditary Hemochromatosis

• Hereditary hemochromatosis is an autosomal recessive disease characterized by excessive iron absorption and accumulation in various organs.
• The disease can be asymptomatic early on but eventually leads to significant organ damage (liver, heart, pancreas, joints).
• Symptoms can mimic other conditions, delaying diagnosis, which often requires genetic and blood tests to determine the presence of excess iron and its impact.

Wilson Disease

• Wilson disease is a genetic disorder where copper cannot be properly metabolized/excreted in bile.
• Copper accumulates in various organs (liver, brain, eyes, and kidneys) leading to progressive dysfunction.
• Serum copper levels are low, and ceruloplasmin (a copper-binding protein) is reduced.
• Increased urinary copper, along with elevated AST, ALT, GGT, and bilirubin, are key indicators.