Podcast
Questions and Answers
What role do bile acids play after being released from the gallbladder?
What role do bile acids play after being released from the gallbladder?
Which statement correctly describes the metabolism of bile acids?
Which statement correctly describes the metabolism of bile acids?
What percentage of bile acids are reabsorbed in the ileum after digestion?
What percentage of bile acids are reabsorbed in the ileum after digestion?
How does the body excrete excess cholesterol?
How does the body excrete excess cholesterol?
Signup and view all the answers
What is a major fate of senescent red blood cells in the bloodstream?
What is a major fate of senescent red blood cells in the bloodstream?
Signup and view all the answers
What is a characteristic feature of pre-hepatic jaundice?
What is a characteristic feature of pre-hepatic jaundice?
Signup and view all the answers
In which type of jaundice does conjugated bilirubin regurgitate back into systemic circulation?
In which type of jaundice does conjugated bilirubin regurgitate back into systemic circulation?
Signup and view all the answers
What typically accompanies hyperbilirubinaemia in intra-hepatic jaundice?
What typically accompanies hyperbilirubinaemia in intra-hepatic jaundice?
Signup and view all the answers
What condition is commonly associated with causes of pre-hepatic jaundice?
What condition is commonly associated with causes of pre-hepatic jaundice?
Signup and view all the answers
What indicates the underlying problem in intra-hepatic jaundice?
What indicates the underlying problem in intra-hepatic jaundice?
Signup and view all the answers
What is the primary color of bile in adults?
What is the primary color of bile in adults?
Signup and view all the answers
Which hormone induces the release of bile from the gallbladder?
Which hormone induces the release of bile from the gallbladder?
Signup and view all the answers
What is one of the principal functions of bile?
What is one of the principal functions of bile?
Signup and view all the answers
Which of the following is a component of bile that aids in fat digestion?
Which of the following is a component of bile that aids in fat digestion?
Signup and view all the answers
What component of bile is responsible for excreting excess cholesterol?
What component of bile is responsible for excreting excess cholesterol?
Signup and view all the answers
What is the main consequence of free iron (Fe2+) released from hemolysis in the body?
What is the main consequence of free iron (Fe2+) released from hemolysis in the body?
Signup and view all the answers
What is the alkaline pH range of bile in adults?
What is the alkaline pH range of bile in adults?
Signup and view all the answers
How does bile facilitate fat digestion?
How does bile facilitate fat digestion?
Signup and view all the answers
Which enzyme is primarily responsible for the degradation of heme to bilirubin?
Which enzyme is primarily responsible for the degradation of heme to bilirubin?
Signup and view all the answers
What is the role of Kupffer cells in relation to bile?
What is the role of Kupffer cells in relation to bile?
Signup and view all the answers
What percentage of the body's bilirubin is derived from red blood cells?
What percentage of the body's bilirubin is derived from red blood cells?
Signup and view all the answers
What complex is formed when haptoglobin binds free hemoglobin?
What complex is formed when haptoglobin binds free hemoglobin?
Signup and view all the answers
What role does UDP-glucuronyl transferase play in bilirubin metabolism?
What role does UDP-glucuronyl transferase play in bilirubin metabolism?
Signup and view all the answers
What is the primary site of bilirubin formation after hemolysis of red blood cells?
What is the primary site of bilirubin formation after hemolysis of red blood cells?
Signup and view all the answers
What condition is indicated by high bilirubin levels making the skin, eyes, and mucous membranes yellow?
What condition is indicated by high bilirubin levels making the skin, eyes, and mucous membranes yellow?
Signup and view all the answers
What substance is formed by the oxidation of bilirubin by colonic bacteria?
What substance is formed by the oxidation of bilirubin by colonic bacteria?
Signup and view all the answers
What is the function of albumin in relation to free hemoglobin?
What is the function of albumin in relation to free hemoglobin?
Signup and view all the answers
What happens to conjugated bilirubin after being excreted into the bile ducts?
What happens to conjugated bilirubin after being excreted into the bile ducts?
Signup and view all the answers
Which characteristic is associated with complete bile duct obstruction?
Which characteristic is associated with complete bile duct obstruction?
Signup and view all the answers
What is the typical duration after birth for newborn jaundice to resolve spontaneously?
What is the typical duration after birth for newborn jaundice to resolve spontaneously?
Signup and view all the answers
Which of the following conditions is characterized by severe unconjugated hyperbilirubinaemia and presents from birth?
Which of the following conditions is characterized by severe unconjugated hyperbilirubinaemia and presents from birth?
Signup and view all the answers
In which syndrome is the enzyme UDP-glucuronyl transferase absent or greatly reduced?
In which syndrome is the enzyme UDP-glucuronyl transferase absent or greatly reduced?
Signup and view all the answers
Which laboratory finding is expected in intra-hepatic jaundice?
Which laboratory finding is expected in intra-hepatic jaundice?
Signup and view all the answers
What complication can arise from elevated levels of free unconjugated bilirubin in newborns?
What complication can arise from elevated levels of free unconjugated bilirubin in newborns?
Signup and view all the answers
What is the treatment commonly used to induce UDP-glucuronyl transferase in Gilbert’s Syndrome?
What is the treatment commonly used to induce UDP-glucuronyl transferase in Gilbert’s Syndrome?
Signup and view all the answers
Which of the following is true regarding Dubin-Johnson Syndrome?
Which of the following is true regarding Dubin-Johnson Syndrome?
Signup and view all the answers
Which factor is an aggravating factor for newborn jaundice in infants?
Which factor is an aggravating factor for newborn jaundice in infants?
Signup and view all the answers
Which lab finding would indicate a post-hepatic jaundice condition?
Which lab finding would indicate a post-hepatic jaundice condition?
Signup and view all the answers
What is the primary function of bile acids in the digestive process?
What is the primary function of bile acids in the digestive process?
Signup and view all the answers
Which bile acids are formed from the metabolism of primary bile acids by gut bacteria?
Which bile acids are formed from the metabolism of primary bile acids by gut bacteria?
Signup and view all the answers
What is the result of the conjugation of primary bile acids in the liver?
What is the result of the conjugation of primary bile acids in the liver?
Signup and view all the answers
What percentage of bile acids typically escapes reabsorption and enters the colon?
What percentage of bile acids typically escapes reabsorption and enters the colon?
Signup and view all the answers
Which of the following enzymes initiates the synthesis of bile acids from cholesterol in the liver?
Which of the following enzymes initiates the synthesis of bile acids from cholesterol in the liver?
Signup and view all the answers
What is the primary role of bile acids in fat digestion?
What is the primary role of bile acids in fat digestion?
Signup and view all the answers
Which characteristic distinguishes intra-hepatic jaundice from pre- and post-hepatic jaundice?
Which characteristic distinguishes intra-hepatic jaundice from pre- and post-hepatic jaundice?
Signup and view all the answers
What type of bilirubin is primarily elevated in post-hepatic jaundice?
What type of bilirubin is primarily elevated in post-hepatic jaundice?
Signup and view all the answers
What triggers the release of bile from the gallbladder?
What triggers the release of bile from the gallbladder?
Signup and view all the answers
Which of the following components of bile is primarily responsible for neutralizing stomach acid?
Which of the following components of bile is primarily responsible for neutralizing stomach acid?
Signup and view all the answers
What function do Kupffer cells serve in relation to bile?
What function do Kupffer cells serve in relation to bile?
Signup and view all the answers
Which of the following best describes hyperbilirubinemia?
Which of the following best describes hyperbilirubinemia?
Signup and view all the answers
Why is bilirubin metabolism important in the body?
Why is bilirubin metabolism important in the body?
Signup and view all the answers
What is a common underlying cause of pre-hepatic jaundice?
What is a common underlying cause of pre-hepatic jaundice?
Signup and view all the answers
Which type of jaundice is characterized by impaired uptake, conjugation, or secretion of bilirubin due to liver cell dysfunction?
Which type of jaundice is characterized by impaired uptake, conjugation, or secretion of bilirubin due to liver cell dysfunction?
Signup and view all the answers
What physiological mechanism causes post-hepatic jaundice?
What physiological mechanism causes post-hepatic jaundice?
Signup and view all the answers
In the context of intra-hepatic jaundice, what biochemical markers are typically elevated?
In the context of intra-hepatic jaundice, what biochemical markers are typically elevated?
Signup and view all the answers
Which of the following is NOT a characteristic of post-hepatic jaundice?
Which of the following is NOT a characteristic of post-hepatic jaundice?
Signup and view all the answers
What is the primary action of haptoglobin in the context of free hemoglobin in the bloodstream?
What is the primary action of haptoglobin in the context of free hemoglobin in the bloodstream?
Signup and view all the answers
Which of the following enzymes is primarily responsible for the conversion of heme to bilirubin?
Which of the following enzymes is primarily responsible for the conversion of heme to bilirubin?
Signup and view all the answers
What is the fate of bilirubin after it is conjugated with glucuronic acid in the liver?
What is the fate of bilirubin after it is conjugated with glucuronic acid in the liver?
Signup and view all the answers
Which of the following conditions would most likely cause jaundice?
Which of the following conditions would most likely cause jaundice?
Signup and view all the answers
What percentage of bilirubin in the body is produced from sources other than red blood cells?
What percentage of bilirubin in the body is produced from sources other than red blood cells?
Signup and view all the answers
Which substance formed during bilirubin metabolism is primarily associated with fecal color?
Which substance formed during bilirubin metabolism is primarily associated with fecal color?
Signup and view all the answers
What is a major symptom associated with hyperbilirubinemia?
What is a major symptom associated with hyperbilirubinemia?
Signup and view all the answers
What is the main role of albumin in bilirubin metabolism?
What is the main role of albumin in bilirubin metabolism?
Signup and view all the answers
What compound is primarily utilized by bacteria in the intestine to further process bilirubin?
What compound is primarily utilized by bacteria in the intestine to further process bilirubin?
Signup and view all the answers
What binds to free haem in the bloodstream to facilitate its detoxification?
What binds to free haem in the bloodstream to facilitate its detoxification?
Signup and view all the answers
What condition is most commonly treated with liver transplant due to severe unconjugated hyperbilirubinaemia?
What condition is most commonly treated with liver transplant due to severe unconjugated hyperbilirubinaemia?
Signup and view all the answers
Which of the following statements correctly describes a feature of Dubin-Johnson Syndrome?
Which of the following statements correctly describes a feature of Dubin-Johnson Syndrome?
Signup and view all the answers
Which lab finding is characteristically abnormal in intra-hepatic jaundice?
Which lab finding is characteristically abnormal in intra-hepatic jaundice?
Signup and view all the answers
What treatment can stimulate UDP-glucuronyl transferase synthesis in patients with Gilbert’s Syndrome?
What treatment can stimulate UDP-glucuronyl transferase synthesis in patients with Gilbert’s Syndrome?
Signup and view all the answers
What complication may arise from untreated elevated levels of free unconjugated bilirubin in newborns?
What complication may arise from untreated elevated levels of free unconjugated bilirubin in newborns?
Signup and view all the answers
How is Crigler-Najjar Syndrome Type II treated under certain circumstances?
How is Crigler-Najjar Syndrome Type II treated under certain circumstances?
Signup and view all the answers
Which condition is characterized by transient hyperbilirubinaemia resolving within 10 days after birth?
Which condition is characterized by transient hyperbilirubinaemia resolving within 10 days after birth?
Signup and view all the answers
What is the most notable lab finding in a patient with post-hepatic jaundice?
What is the most notable lab finding in a patient with post-hepatic jaundice?
Signup and view all the answers
What aggravating factor can exacerbate jaundice in newborns?
What aggravating factor can exacerbate jaundice in newborns?
Signup and view all the answers
In which type of jaundice is the urine urobilinogen absent?
In which type of jaundice is the urine urobilinogen absent?
Signup and view all the answers
Study Notes
What is Bile?
- Bile is a fluid produced by the liver, approximately 500mL/day in adults.
- It is typically yellow-green and alkaline (pH 7.5-8).
- It is stored in the gallbladder and released in response to cholecystokinin (CCK).
- CCK is released from I cells in the duodenum after eating a meal containing nutrients.
- Bile is essential for fat digestion and absorption, excretion of excess cholesterol and metabolites, and neutralisation of stomach acid.
Bile Composition
- Bile contains bile acids, bile pigments, cholesterol, drugs and their metabolites, and particulate matter.
- Particulate matter is removed from the bloodstream by Kupffer cells in the liver.
Bile and Fat Digestion
- Bile acids act as detergents, emulsifying fats in food.
- Bile acids are amphipathic, with hydrophilic and hydrophobic regions.
- They form micelles around fat droplets, with the hydrophobic sides facing the fat and the hydrophilic sides facing outwards.
- Pancreatic amylase can enter micelles and digest triglycerides into monoglycerides and fatty acids.
Bile Acid Metabolism
- Primary bile acids, cholic acid and chenodeoxycholic acid, are synthesised in the liver from cholesterol.
- They are conjugated to glycine or taurine, forming conjugated primary bile acids, and stored in the gallbladder.
- They are released in response to a meal to facilitate fat digestion and absorption.
- Primary bile acids are converted to secondary bile acids by bacteria in the colon.
- Bile acids provide a pathway for excess cholesterol excretion from the body.
Bilirubin
- Bilirubin is a natural degradation product of haem.
- Red blood cells (RBCs) have a lifespan of 60-120 days.
- Most senescent RBCs are destroyed extravascularly (in the liver, spleen, or bone marrow) through phagocytosis or lysis.
- Intravascular haemolysis is rare, usually occurring as a consequence of disease.
- Released haem is toxic, requiring detoxification through metabolism to bilirubin.
- 75% of bilirubin is derived from RBCs, the remainder from other heme-containing proteins (eg., myoglobin, cytochromes).
Formation of Bilirubin
- Haemoglobin from RBCs is broken down into globin, haem, and bilirubin during phagocytosis and hemolysis.
- Iron (Fe2+) is recycled for erythropoiesis.
- Bilirubin is a waste product that needs to be excreted.
Handling of Free Haemoglobin
- Free haem in the blood is toxic.
- Detoxification occurs by binding to serum proteins.
- Haptoglobin binds to free haemoglobin, forming a complex that is metabolised in the liver and spleen, producing iron-globin and bilirubin. This complex also prevents iron loss in the urine.
- Haemopexin binds to the free haem, forming a complex that is taken up by the liver for iron storage.
- Albumin binds to oxidized haem, forming Met-haemalbumin.
Degradation of Haem to Bilirubin
- Degradation occurs mostly in the spleen, requiring two enzymes: heme oxygenase (HMOX) and biliverdin reductase (BVRA).
- Haem is converted to biliverdin (green pigment) by HMOX.
- Biliverdin is then converted to bilirubin (yellow pigment) by BVRA.
Metabolism of Bilirubin
- The liver takes up bilirubin through facilitated diffusion via the OATP transporter.
- Bilirubin binds to cytoplasmic proteins (ligandin and protein Y) in hepatocytes, preventing efflux back into the blood.
- Bilirubin is conjugated with glucuronic acid by UDP-glucuronyl transferase (UDP-glucuronosyltransferase), making it water-soluble.
Metabolism of Bilirubin (Continued)
- Conjugated bilirubin is secreted into bile ducts through active transport via MRP-3.
- Bile is excreted from the liver into the gut.
- Glucuronidases in colonic bacteria de-conjugate bilirubin to urobilinogen (colourless).
- Urobilinogen is either oxidized by bacteria to stercobilin (brown pigment) and excreted in feces, or reabsorbed into the portal blood.
- Reabsorbed urobilinogen is partially excreted in urine as urobilin.
Summary of Bilirubin Formation and Fate
- Haem from RBC hemolysis is converted to bilirubin.
- Bilirubin is transported in the bloodstream bound to albumin.
- The liver takes up bilirubin, conjugates it, and excretes it into bile.
- Bilirubin is converted to urobilinogen in the intestinal tract.
- Urobilinogen is either reabsorbed and excreted in urine as urobilin or excreted in feces as stercobilin.
Jaundice
- Jaundice presents as yellowing of the skin, whites of the eyes, and mucous membranes due to hyperbilirubinemia.
- Typically occurs when serum bilirubin levels exceed 35 µM/L (normal 17 µM/L).
- Usually indicates underlying disease involving abnormal heme metabolism, liver dysfunction, or biliary tract obstruction.
- Can cause complications such as urticaria, abdominal pain, pale feces, dark urine, and neurological damage (kernicterus).
- Treatment depends on the underlying cause.
Classification of Jaundice
- There are three categories of jaundice based on the site of pathology.
- Pre-hepatic (haemolytic): Bilirubin production exceeds the liver’s uptake capacity.
- Intra-hepatic (hepatocellular): Bilirubin cannot be taken up, conjugated, or excreted due to hepatocellular damage.
- Post-hepatic (cholestatic): Obstruction to biliary flow causes conjugated bilirubin to be regurgitated back into circulation.
Pre-hepatic Jaundice
- Also known as haemolytic jaundice or hematogenous jaundice.
- Excess bilirubin production following haemolysis.
- Excess RBC lysis is often due to autoimmune disease.
- High plasma levels of unconjugated bilirubin.
Intra-hepatic Jaundice
- Also known as hepatocellular jaundice.
- Impaired uptake, conjugation, or secretion of bilirubin.
- Reflects generalized liver cell (hepatocyte) dysfunction.
- Hyperbilirubinaemia is often accompanied by other abnormal biochemical markers of liver function.
Post-hepatic Jaundice
- Also known as obstructive jaundice or choleostatic jaundice.
- Caused by obstruction to the biliary tract.
- Plasma bilirubin is conjugated.
- Other bile constituents also accumulate in the plasma.
- Characterized by pale stools and dark urine.
Differential Diagnosis of Jaundice:
-
Pre-hepatic
- Conjugated bilirubin: Present
- ALT or AST: Normal
- Alkaline phosphatase (ALP): Normal
- Urine bilirubin: Absent
- Urine urobilinogen: Present
-
Intra-hepatic
- Conjugated bilirubin: Increased
- ALT or AST: Increased
- Alkaline phosphatase (ALP): Normal
- Urine bilirubin: Present
- Urine urobilinogen: Present
-
Post-hepatic
- Conjugated bilirubin: Increased
- ALT or AST: Normal
- Alkaline phosphatase (ALP): Increased
- Urine bilirubin: Present
- Urine urobilinogen: Absent
Newborn Jaundice
- Common, particularly in premature infants.
- Occurs 2-4 days after birth due to immature enzymes involved in bilirubin conjugation.
- Typically resolves within 10 days of life.
Complications of Newborn Jaundice
- Kernicterus: Occurs when unbound unconjugated bilirubin deposits in the brain, causing encephalopathy.
- Aggravating factors: Haemolysis, breastfeeding, sulphonamides, antibiotics.
Treatment of Newborn Jaundice
- Often resolves without treatment.
- Phototherapy: Converts bilirubin to a water-soluble, non-toxic form.
- Phenobarbitone: Induces synthesis of UDP-glucuronyl transferase.
- Exchange blood transfusion: Removes excess bilirubin.
- Pathological jaundice (within 24 hours of birth or lasting over 10 days) indicates an underlying condition.
Gilbert’s Syndrome
- Most common inherited disorder of bilirubin conjugation, presenting with mild, fluctuating unconjugated hyperbilirubinaemia.
- Onset typically during adolescence due to sex hormone changes.
- Caused by reduced UDP-glucuronyl transferase activity, preventing bilirubin conjugation.
- Often treated with phenobarbitone to stimulate UDP-glucuronyl transferase activity.
Crigler-Najjar Syndrome
- Rare autosomal recessive disorder presenting with severe unconjugated hyperbilirubinemia from birth.
- Caused by mutations in the UDP-glucuronyl transferase gene.
- Type I: Complete absence of the enzyme.
- Type II: Marked reduction in enzyme activity.
- High risk of kernicterus.
- Treatment: Liver transplant (Type I), phenobarbitone or phototherapy (Type II).
Dubin-Johnson Syndrome
- Benign genetic disorder presenting with conjugated hyperbilirubinaemia.
- Presents with mild, recurrent jaundice.
- Caused by a mutation in the gene coding for MRP-2, resulting in impaired biliary secretion of conjugated bilirubin.
- Jaundice can worsen with aggravating factors.
- Treatment: Not usually necessary.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on the role of bile acids and the different types of jaundice. This quiz will cover the metabolism of bile acids, reabsorption rates in the ileum, and the characteristics of pre-hepatic and intra-hepatic jaundice. Challenge yourself and see how well you understand these important concepts in human physiology.
