Podcast
Questions and Answers
Which metabolic process in the liver is primarily responsible for the detoxification of harmful substances?
Which metabolic process in the liver is primarily responsible for the detoxification of harmful substances?
What percentage of plasma proteins does albumin account for by weight in the blood?
What percentage of plasma proteins does albumin account for by weight in the blood?
Which of the following proteins is specifically noted for being a sensitive indicator of protein-nutrition status?
Which of the following proteins is specifically noted for being a sensitive indicator of protein-nutrition status?
Which structure contributes to the metabolism and storage functions of the liver?
Which structure contributes to the metabolism and storage functions of the liver?
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In which part of the body is the liver located?
In which part of the body is the liver located?
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Which of the following nonprotein nitrogens is primarily produced by the liver?
Which of the following nonprotein nitrogens is primarily produced by the liver?
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What is the principal role of albumin in the circulatory system?
What is the principal role of albumin in the circulatory system?
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What is the first step in the formation of bile pigments from senescent erythrocytes?
What is the first step in the formation of bile pigments from senescent erythrocytes?
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What is the earliest marker of HAV infection?
What is the earliest marker of HAV infection?
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What percentage of patients infected with HBV will recover completely?
What percentage of patients infected with HBV will recover completely?
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Which serological marker is used as the diagnostic marker for current infection of hepatitis B?
Which serological marker is used as the diagnostic marker for current infection of hepatitis B?
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How long after infection does HBsAg typically appear in the blood?
How long after infection does HBsAg typically appear in the blood?
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What can be used to monitor HAV infection aside from serum ALT levels?
What can be used to monitor HAV infection aside from serum ALT levels?
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What is the fatality rate following HBV infection?
What is the fatality rate following HBV infection?
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What percentage of chronic HBV carriers infected perinatally may die from cirrhosis or liver cancer?
What percentage of chronic HBV carriers infected perinatally may die from cirrhosis or liver cancer?
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When do ALT levels typically return to the reference interval after an initial elevation for HAV infection?
When do ALT levels typically return to the reference interval after an initial elevation for HAV infection?
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What does a prolonged Prothrombin Time (PT) typically indicate?
What does a prolonged Prothrombin Time (PT) typically indicate?
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Which of the following is NOT a virus that primarily causes hepatitis in humans?
Which of the following is NOT a virus that primarily causes hepatitis in humans?
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Which serum protein is significantly decreased in chronic active hepatitis?
Which serum protein is significantly decreased in chronic active hepatitis?
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What condition is indicated by elevated blood ammonia levels in adult patients?
What condition is indicated by elevated blood ammonia levels in adult patients?
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What is the primary site of infection for Hepatitis viruses A, B, C, D, and E?
What is the primary site of infection for Hepatitis viruses A, B, C, D, and E?
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What does a decrease in serum urea levels indicate in the context of liver disease?
What does a decrease in serum urea levels indicate in the context of liver disease?
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Which of the following routes is NOT associated with Hepatitis A and E?
Which of the following routes is NOT associated with Hepatitis A and E?
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What role does prothrombin play in the blood coagulation system?
What role does prothrombin play in the blood coagulation system?
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What is the primary role of alkaline phosphatase (ALP) enzymes in the body?
What is the primary role of alkaline phosphatase (ALP) enzymes in the body?
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Which condition causes the most significant increase in alkaline phosphatase (ALP) activity?
Which condition causes the most significant increase in alkaline phosphatase (ALP) activity?
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Which liver enzyme is primarily associated with glutathione metabolism and amino acid resorption from glomerular filtrate?
Which liver enzyme is primarily associated with glutathione metabolism and amino acid resorption from glomerular filtrate?
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In acute liver necrosis, which enzyme typically exhibits a greater increase?
In acute liver necrosis, which enzyme typically exhibits a greater increase?
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When is serum gamma-glutamyltransferase (GGT) elevated compared to other liver enzymes during liver disease onset?
When is serum gamma-glutamyltransferase (GGT) elevated compared to other liver enzymes during liver disease onset?
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Which condition typically does not result in an increase in alkaline phosphatase (ALP) activity despite liver involvement?
Which condition typically does not result in an increase in alkaline phosphatase (ALP) activity despite liver involvement?
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Which of the following conditions would NOT typically cause an elevation of serum transaminases?
Which of the following conditions would NOT typically cause an elevation of serum transaminases?
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What is the primary mechanism for bilirubin metabolism in hepatocytes?
What is the primary mechanism for bilirubin metabolism in hepatocytes?
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What serum bilirubin level is typically associated with the onset of jaundice?
What serum bilirubin level is typically associated with the onset of jaundice?
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What laboratory measurement can be particularly useful when only liver involvement is suspected?
What laboratory measurement can be particularly useful when only liver involvement is suspected?
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Which of the following conditions leads to unconjugated hyperbilirubinemia due to a defect in bilirubin uptake?
Which of the following conditions leads to unconjugated hyperbilirubinemia due to a defect in bilirubin uptake?
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What type of jaundice is primarily caused by obstruction in the biliary outflow tract?
What type of jaundice is primarily caused by obstruction in the biliary outflow tract?
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Which liver function test is NOT typically used to identify liver disease?
Which liver function test is NOT typically used to identify liver disease?
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What is the typical serum concentration of conjugated bilirubin in a normal adult?
What is the typical serum concentration of conjugated bilirubin in a normal adult?
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Which disease is associated with the inability to secrete conjugated bilirubin into the biliary system?
Which disease is associated with the inability to secrete conjugated bilirubin into the biliary system?
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What is the primary change in bilirubin metabolism observed in hemolytic anemia?
What is the primary change in bilirubin metabolism observed in hemolytic anemia?
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Study Notes
Liver Diseases & Liver Function Tests
- The lecture covered liver diseases and liver function tests.
- The presentation was given by Prof. Dr. Halil RESMİ on Tuesday, October 8, 2024, and Wednesday, October 9, 2024.
Metabolism of the Liver
- Liver metabolism includes carbohydrate metabolism, nitrogen metabolism, bile acid formation, bilirubin metabolism, lipid metabolism, blood protein synthesis, detoxification, metabolic end-product excretion, and storage function.
Anatomy of the Liver
- The liver is the largest organ in the body (weighing 1.2 to 1.5 kg).
- It's divided into two lobes.
- Located in the abdominal cavity, positioned below the diaphragm.
Liver Topography
- Demonstrated the location of the liver relative to other abdominal organs
- Showing the right and left lobes of the liver.
- Including the gallbladder, duodenum, and large intestine.
Hepatic Lobule
- The hepatic lobule is a hexagon-shaped unit of liver tissue.
- The portal triad contains the bile duct, portal vein, and hepatic artery.
- Sinusoids are capillaries that carry blood through the lobule.
- Hepatocytes are liver cells.
- Kupffer cells are macrophages within the sinusoids, involved in removing debris and pathogens.
- The central vein (hepatic vein) carries blood out of the lobule.
Biliary Canaliculi
- The biliary tree's topology was shown.
- Canalicular network: ~1 µm.
- Interlobular bile ducts: 10 µm-100 µm.
- Large and Common bile ducts: >1000 µm.
Liver Cells
- The liver's primary cells are hepatocytes and Kupffer cells.
- Hepatocytes are responsible for the liver's metabolic functions.
Protein Metabolism in the Liver
- Most serum proteins are synthesized in the liver (with exceptions like gamma globulins and hemoglobin in adults).
- Many liver-synthesized proteins enter the bloodstream.
Major Plasma Proteins
- A table presented various major plasma proteins, their concentrations, molecular weights, and properties.
Albumin
- One of the liver's most important proteins.
- Found in plasma concentrations of 4.0-5.0 g/dL.
- Represents 50-60% of total plasma proteins by weight.
- Plays a role in maintaining oncotic pressure.
- Transports calcium, unconjugated bilirubin, free fatty acids, drugs, and steroid hormones.
Prealbumin (Transthyretin)
- A minor plasma protein produced by the liver.
- A sensitive indicator of protein-nutritional status.
- Measurement of prealbumin and albumin aids in diagnosing and tracking malnutrition.
Nonprotein Nitrogen
- Urea, creatinine, ammonia, and uric acid make up 70-75% of serum nonprotein nitrogen.
- Most nonprotein nitrogen metabolism happens in the liver.
- Urea is produced by the liver.
Urea Cycle
- A diagram illustrating the urea cycle, a metabolic pathway in the liver.
- The cycle converts ammonia to urea, a less toxic compound.
Bile Pigment Formation
- Senescent erythrocytes (old red blood cells) are phagocytozed by the reticuloendothelial system (RES).
- Hemoglobin is released from the RBCs.
- Globin and heme are separated.
- The heme portion gets converted into bilirubin.
- Released iron is bound by transferrin and transported back to the liver and bone marrow.
- Globin chains are degraded into amino acids by protein-degrading enzymes.
- Bilirubin (unconjugated) binds to albumin and transported to hepatocytes.
- In hepatocytes, bilirubin is converted to bilirubin glucuronide (conjugated).
- Bilirubin glucuronide, also called conjugated bilirubin, is excreted to the biliary canaliculi.
- Normal adult blood serum contains only a small amount (0.0-0.3 mg/dL) of conjugated bilirubin.
- Approximately 0.2-0.8 mg/dL of unconjugated bilirubin is present in the blood.
Liver Function Alterations During Disease (Jaundice)
- Jaundice (icterus): A general term for abnormal bilirubin metabolism or retention, leading to yellow discoloration of skin, mucous membranes, and sclera (white of the eyes).
- Types of Jaundice: (1) Prehepatic, (2) Hepatic, (3) Posthepatic.
Types of Jaundice
- Prehepatic: Caused by increased breakdown of red blood cells.
- Hepatic: Disorders stemming from liver dysfunction in processing bilirubin.
- Posthepatic: Obstructions blocking the normal flow of bile.
Mechanisms of Hyperbilirubinemia
- Different processes leading to elevated bilirubin levels in the blood, including impaired bilirubin uptake, conjugation, secretion, and biliary obstruction.
Liver Function Tests
- List of liver function tests commonly used for diagnostics: Enzymes (liver enzymes), bilirubin, serum proteins, prothrombin time (PT), urea and ammonia.
Liver Enzymes
- Alkaline phosphatase (ALP)
- Gamma-glutamyltransferase (GGT)
- Aspartate aminotransferase (AST/ALT)
- Lactate dehydrogenase (LDH)
Alkaline Phosphatase (ALP)
- ALP is a group of enzymes catalyzing the hydrolysis of monophosphate esters at alkaline pH.
- Present in most tissues, but liver, bone, intestines, kidney, and placenta show higher activity.
- High ALP activity may suggest biliary obstruction, notably extrahepatic (e.g., gallstones). Intrahepatic obstruction shows mild increase (2-3 fold).
- Hepatocyte necrosis doesn't raise ALP unless associated biliary disease is present.
- Common bone diseases causing elevated ALP include Paget's disease, rickets, and osteomalacia.
Gamma-Glutamyltransferase (GGT)
- GGT is a membrane-bound enzyme involved in glutathione metabolism and amino acid reabsorption.
- Mostly found in renal tissue, its serum levels rise with liver conditions.
- Elevated often before other liver enzymes in certain liver diseases like acute cholecystitis, pancreatitis, liver necrosis, and liver metastases.
- Helps distinguish liver disease from other conditions causing high ALP.
AST & ALT
- AST and ALT catalyze the conversion of aspartate and alanine respectively.
- Highest ALT levels detected in the liver, AST levels comparable.
- Both enzymes increase rapidly after viral infection, typically staying elevated in the blood for 1-2 weeks.
- Notably elevated ALT level in acute liver necrosis compared to AST.
- Cirrhotic liver necrosis usually indicates elevated ALT/AST but typically not exceeding 300 U/L.
Lactate Dehydrogenase (LDH)
- LDH activity is highest in the kidney and heart.
- Usefulness in liver diagnosis is limited to cases where only liver involvement is suspected.
- Erythrocytes have high LDH; hemolyzed serum samples affect LDH measurements.
Serum Proteins in Evaluation of Liver Function
- Serum albumin levels decrease in chronic liver disease.
- Albumin/globulin ratio (IgM & IgG) is also reduced in chronic active hepatitis.
- Decreased serum albumin isn't specific to liver disease; it can be seen in malabsorption, malnutrition, and renal disease.
- Coagulation factors synthesized in the liver are significantly reduced during liver disease.
Prothrombin Time (PT)
- Prothrombin is a crucial blood coagulation factor produced in the liver.
- Conversion of prothrombin to thrombin is critical for fibrin formation.
- PT measures how long blood takes to clot, measured in seconds (12-15 sec).
- A prolonged PT indicates a loss of clotting factors, often linked to liver damage, such as cirrhosis.
Urea & Ammonia in Liver Function Evaluation
- Ammonia, a toxic metabolite, is converted to urea (soluble and less toxic) in the liver.
- Urea is subsequently released into the bloodstream and expelled via urine.
- Elevated blood ammonia is observed in severe, late-stage liver diseases like cirrhosis.
- Liver disease often results in low serum urea levels (if kidney function is normal).
Viral Hepatitis
- Hepatitis A, B, C, D, and E are common viral hepatitis causes.
- HAV causes primarily acute, self-limiting hepatitis.
- HBV, HCV, & HDV can lead to both acute and chronic infections, risking cirrhosis and liver cancer.
- Hepatitis E also causes mainly acute hepatitis.
Hepatitis A
- Worldwide, approximately 25% of acute hepatitis cases are due to HAV.
- HAV has 8 genotypes with 4 impacting humans.
- HAV is antigenically homogenous, possessing a single serotype.
- HAV replicates in the liver, its excretion route being through the bile to the intestine.
- HAV concentrations are highest in stool samples.
Diagnosis of HAV Infection
- The earliest marker of HAV infection is IgM anti-HAV.
- Past HAV infection is proven by the presence of IgG anti-HAV.
- PCR tests can identify HAV contamination.
Monitoring HAV Infection
- Serum ALT and bilirubin levels or IgM anti-HAV help monitor infection progression.
- Normal ALT levels return to the reference range 5-7 weeks after initial elevation.
- IgM anti-HAV becomes undetectable within a few months.
Clinical Virological and Serological Events Associated with Hepatitis A Virus Infection
- A graph illustrating the viral load, symptoms, and immunological markers over time during an HAV infection.
- Time-related dynamics of HAV infection: viremia, symptoms, increasing anti-HAV concentration
Hepatitis B
- Hepatitis B infection has an approximate 0.5-1.5% fatality rate.
- Most patients recover completely. However. greater than 10% of HBV-infected individuals become chronic carriers.
- Approximately 25% of chronic HBV carriers perinatally will contract cirrhosis or liver cancer.
- Hepatitis B vaccination is very good at preventing HBV infection.
Lab Tests for HBV
- Lab findings in acute HBV include elevated ALT and AST, as well as serum bilirubin.
- A prolonged prothrombin time signifies potential for fulminant liver failure (0.1-0.5% of acute HBV cases)
Serological Markers
- A table outlining various Hepatitis B serological markers (antigens and antibodies) and what they correlate with (e.g., active infection, immunity), providing a diagnostic overview.
Diagnostic Tests for HBV
- HBsAg (Hepatitis B surface antigen) detection is the primary diagnostic tool for current HBV infection; it appears within approximately 4 weeks of infection.
- HBsAg peaks at about 8–12 weeks after infection, declining during the resolution phase and generally becoming undetectable within 6 months.
Hepatits Serological Events Associated With Viral Infection
- A graph demonstrating the course of Hepatitis B infection regarding the dynamics of serological markers over time.
- Showing time-related dynamics of HBV infection including viremia, symptoms, and the changing levels of various serological markers
Summary of Serological Markers
- A table listing possible results from different serological tests (positive/negative for different markers) and the corresponding clinical health status of the patient, classified as susceptible, immune (due to vaccination or natural infection), acutely infected, or chronically infected.
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Description
Test your knowledge on liver metabolism, detoxification processes, and important plasma proteins. This quiz covers various functions of the liver, including its role in the circulatory system and hepatitis markers. Perfect for students studying biology or health sciences.
