Bilirubin Metabolism Rajendra

Bilirubin metabolism including liver function test for medical students

1. BILIRUBIN METABOLISM Rajendra Dev Bhatt Clinical Biochemist & Lecturer Dhulikhel Hospital-Kathmandu University H ospital 3/1/2018 Rajendra Dev Bhatt

2. Haemoglobin Haemoglobin is a conjugated protein made up of four subunits Each subunit contains a haem group and a polypeptide chain The h a em gr o up i s mad e u p o f p o rp h yr i n and a ferrous ion Ha e m o glo b in can rever s i b ly c o m b i n e with oxygen , and transports oxygen in the body 3/1/2018 Rajendra Dev Bhatt

3. Catabolism of H aemoglobin Wh e n lif e -span o f RBCs i s ov e r , th e y are broken down in reticulo -endothelial system Haem and globin are separated. Globin is broken down into amino acids. The iron liberated from heme is reutilized. The porphyrin ring is broken down in reticuloendothelial (RE) cells of liver, spleen and bone marrow to bile pigments, mainly bilirubin Generation of Bilirubin 3/1/2018 Rajendra Dev Bhatt

4. 1. Generation of Bilirubin Cont… About 6 g of Hb is broken down per day, from which about 250 mg of bilirubin is formed From myoglobin and other heme containing proteins , another 50 mg of bilirubin is formed . Approximately 35 mg of bilirubin is formed from 1 g of Hb . A total of 300 mg of bilirubin is formed everyday; of which 80% is from destruction of old RBCs, 10% from ineffective erythropoiesis and the rest 10% from degradation of myoglobin and other heme containing proteins . 3/1/2018 Rajendra Dev Bhatt

5. 1. Generation of Bilirubin Cont… Heme is degraded primarily by a microsomal enzyme system; heme oxygenase . It requires molecular oxygen and NADPH The oxygenase enzyme specifically catalyzes the cleavage of the alpha methenyl bridge , which is linking the pyrrole rings I and II. The linear tetrapyrrole formed is biliverdin which is green in color. In mammals it is further reduced to bilirubin , a red-yellow pigment , by an NADPH dependent biliverdin reductase . 3/1/2018 Rajendra Dev Bhatt

6. 1. Generation of Bilirubin Cont… In the first reaction, a bridging methylene group is cleaved by heme oxygenase to form Linear Biliverdin from Cyclic Heme molecule. Fe 2 + is released from the ring in this process. 3/1/2018 Rajendra Dev Bhatt

7. 1. Generation of Bilirubin Cont… RBCs Breakdown Hemoglobin Produces & Breakdown Heme Biliverdin Bilirubin Heme Oxygenase Biliverdin Reductase 3/1/2018 Rajendra Dev Bhatt

8. 2. Transport to Liver The bilirubin formed in the reticuloendothelial cells is insoluble in water . The lipophilic bilirubin is therefore transported in plasma bound to a lbumin . One molecule of albumin can bind 2 molecules of bilirubin. Albumin binds bilirubin in loose combination . So when present in excess, bilirubin can easily dissociate from albumin. The binding sites for bilirubin on albumin can be occupied by aspirin , penicillin , etc. Such drugs can, therefore , displace bilirubin from albumin. Hence, care should be taken while administering such drugsto newborn babies to avoid kernicterus . When the albumin–bilirubin complex reaches the sinusoidal surface of the liver, the bilirubin is taken up. 3/1/2018 Rajendra Dev Bhatt

9. 2. Transport to Liver Bilirubin is not very water-soluble, so most of it is carried to the liver bound to albumin. 3/1/2018 Rajendra Dev Bhatt

10. 3. Conjugation in Liver Inside the liver cell, the bilirubin is conjugated with glucuronic acid, to make it water soluble. The first carbon of glucuronic acid is combined with the carboxyl group of the propionic acid side chains of the bilirubin molecule . About 80% molecules are in the diglucuronide form, while 20% are monoglucuronides . Drugs like primaquine , novobiocin , chloramphenicol , androgens and pregnanediol may interfere in this conjugation process and may cause jaundice . 3/1/2018 Rajendra Dev Bhatt

11. 3. Conjugation in Liver 3/1/2018 Rajendra Dev Bhatt

12. Unconjugated bilirubin : Bilirubin that are not conjugated with gluconic acid , also called hemobilirubin , indirect bilirubin . conjugated bilirubin: Bilirubin that are conjugated with gluconic acid, also called hepatic bilirubin , direct bilirubin. 3/1/2018 Rajendra Dev Bhatt

13. Unconjugated VS Conjugated Bilirubin FEATURE Unconjugated Conjugated Normal serum level More Less (less than 0.2mg/dl) Water solubility Absent Present Affinity to lipids (alcohol solubilty) Present Absent Serum albumin binding High Low Van den Bergh reaction Indirect (Total minus direct) Direct Reanal excretion Absent Present Affinity to brain tissue Present (kernicterus) Absent 3/1/2018 Rajendra Dev Bhatt

14. 4. Excretion of Bilirubin to Bile The water soluble conjugated bilirubin is excreted into the bile by an active process and this occurs against a concentration gradient. This is the rate limiting step in the catabolism of heme . It is induced by phenobarbitone . Excretion of conjugated bilirubin into bile is mediated by an ATP binding cassette protein which is called Multispecific organic anion transporter (MOAT), located in the plasma membrane of the biliary canaliculi . 3/1/2018 Rajendra Dev Bhatt

15. 4. Excretion of Bilirubin to Bile Cont.. 3/1/2018 Rajendra Dev Bhatt

16. 5.Fate of Conjugated Bilirubin in Intestine The conjugated bilirubin reaches the intestine through the bile. In the small intestine, conjugated bilirubin is poorly reabsorbed and partly hydrolyzed back to unconjugated bilirubin by catalytic action of bacterial ß- glucuronidases . In the distal ileum and colon, anaerobic flora mediate further catabolism of bile pigments. hydrolysis of conjugated bilirubin to unconjugated bilirubin by bacterial β - glucuronidases ; multistep hydrogenation (reduction) of unconjugated bilirubin to form colorless urobilinogens (44 Hydrogen) Further reduction of UBG leads to formation of stercobilinogen (SBG,48 hydrogen) The SBG is mostly excreted through feces (250-300 mg/day). Upto 20 % of urobilinogen produced daily is reabsorbed from the intestine & enters the entero -hepatic circulation. 3/1/2018 Rajendra Dev Bhatt

17. 5.Fate of Conjugated Bilirubin in Intestine 3/1/2018 Rajendra Dev Bhatt

18. 6. Final Excretion UBG and SBG are both colorless compounds but are oxidized to colored products, urobilin (42 hydrogen) or stercobilin (46 hydrogen) respectively by atmospheric oxidation. Black color is seen in constipation. If intestinal flora is decreased by prolonged administration of antibiotics, bilirubin is not reduced to bilinogens , and in the large gut, it is re-oxidized by O2 to form biliverdin . Then green tinged feces is seen, especially in children. 3/1/2018 Rajendra Dev Bhatt

19. BLOOD CELLS LIVER Bilirubin diglucuronide ( water-soluble ) 2 UDP-glucuronic acid via bile duct to intestines Stercobilin excreted in feces Urobilinogen formed by bacteria KIDNEY Urobilin excreted in urine CO Biliverdin Heme oxygenase O 2 Bilirubin ( water-insoluble ) NADP + NADPH Biliverdin reductase Heme Globin Hemoglobin reabsorbed into blood Bilirubin ( water-insoluble ) via blood to the liver INTESTINE Catabolism of hemoglobin unconjugated 3/1/2018 Rajendra Dev Bhatt

20. Summary of bilirubin metabolism Old red cells are major source of hemeproteins Breakdown of heme to bilirubin occur in macrophage of reticuloendithelial system ( tissue macrophages, spleen and liver). Unconjugated bilirubin is transported through blood ( complex to albumin) to liver. Bilirubin is taken into liver and conjugate with glucuronic acid. Bile is secreted into intestine where glucuronic acid is removed and the resulting bilirubin is converted to urobilinogen. A portion of urobilinogen is reabsorbed into blood, where it is converted to the yellow urobilin and excreted by kidneys. Urobilinogen is oxidized by intestinal bacteria to the brown stercobilin . 3/1/2018 Rajendra Dev Bhatt

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22. JAUNDICE Jaundice is a yellow discoloration of the skin, mucous membranes , and sclera caused by increased amounts of bilirubin in the blood. Jaundice is a sign of an underlying disease process . Jaundice results from the accumulation of bilirubin. Hyperbilirubinemia may be due to abnormalities in the formation, transport, metabolism, and excretion of bilirubin. Total serum bilirubin is normally 0.2–1.2 mg/dL and jaundice may not be recognizable until levels are about 3 mg/dL . In the normal adult the rate of systemic bilirubin production is equal to the rates of hepatic uptake, conjugation, and biliary excretion. Jaundice occurs (bilirubin levels may reach 30-40 mg/dL in severe disease) when the equilibrium between bilirubin production and clearance is disturbed by one or more of the following mechanisms. 3/1/2018 Rajendra Dev Bhatt

23. JAUNDICE (1) Excessive production of bilirubin, (2) Reduced hepatic uptake, (3) Impaired conjugation, (4) Decreased hepatocellular excretion, and (5)Impaired bile flow (both intra hepatic and extra hepatic). The first three mechanisms produce unconjugated hyperbilirubinemia, and the latter two produce predominantly conjugated hyperbilirubinemia. More than one mechanism may operate to produce jaundice, especially in hepatitis, which may produce Unconjugated and conjugated hyperbilirubinemia. 3/1/2018 Rajendra Dev Bhatt

24. Classification of jaundice Pre-hepatic (before bile is made in the liver) Jaundice in these cases is caused by rapid increase in the breakdown and destruction of the red blood cells (hemolysis), overwhelming the liver’s ability to adequately remove the increased levels of bilirubin from the blood. Jaundice in these cases is caused by rapid increase in destruction of the red blood cells (hemolysis), overwhelming the liver’s ability to adequately remove the increased levels of bilirubin from the blood. 3/1/2018 Rajendra Dev Bhatt

25. 1. Pre-hepatic Jaundice Cont… Examples of conditions with increased breakdown of red blood cells include: -Malaria, -Sickle cell crisis, - Spherocytosis , -Thalassemia, -Glucose-6-phosphate dehydrogenase deficiency -Drugs or other toxins, and –Autoimmune disorders. 3/1/2018 Rajendra Dev Bhatt

26. 2.Hepatic (the problem arises within the liver) Jaundice in these cases is caused by the liver’s inability to properly metabolize and excrete bilirubin. Causes –Viral – hepatitis A, B, or C, yellow fever, Bacterial sepsis, tuberculosis, –Alcohol, Drugs e.g. estrogens, contraceptive pills and Pregnancy –Carcinoma: metastases. Lymphoma. Adenocarcinoma of kidney -Chronic active hepatitis 3/1/2018 Rajendra Dev Bhatt

27. 3.Post-hepatic (after bile has been made in the liver) Jaundice in these cases, also termed obstructive jaundice , is caused by conditions which interrupt the normal drainage of conjugated bilirubin in the form of bile from the liver into the intestines. The obstruction may be intrahepatic or extra hepatic. Causes of obstructive jaundice include: a) Intra hepatic Obstruction - Biliary atresia -Primary Biliary Cirrhosis -Malignant infiltration of ducts 3/1/2018 Rajendra Dev Bhatt

28. 3.Post-hepatic Jaundice Cont… Causes of obstructive jaundice include: b) Extra hepatic obstruction -Gallstones in the bile ducts, -cancer (pancreatic and gallbladder/bile duct carcinoma), -strictures of the bile ducts, -Pressure on the common bile duct from enlarged lymph nodes, - cholangitis , -congenital malformations, -pancreatitis, 3/1/2018 Rajendra Dev Bhatt

29. Congenital conditions that may cause jaundice Crigler-Najjar syndrome: An inherited condition that may lead to severe Unconjugated hyperbilirubinemia ( high bilirubin concentrations); a gene mutation leads to a deficiency in an enzyme necessary for bilirubin conjugation. Unconjugated bilirubin Conjugates in the liver in the presence of an enzyme UDP- glucuronosyltransferase . In Crigler - Najjar patients the enzyme is either inactive (type I) or severely reduced (type II). Therefore bilirubin cannot be excreted into the bile and remains in the blood. The high plasma level of Unconjugated bilirubin leads to jaundice and may lead to kernicterus (bilirubin encephalopathy)  . 3/1/2018 Rajendra Dev Bhatt

30. Congenital conditions that may cause jaundice 2.Dubin-Johnson syndrome: an inherited disorder that causes the retention of conjugated bilirubin (and other compounds that turn the liver black) in liver cells; patients may have intermittent jaundice. This is an autosomal recessive disorder in which patients have an increase in  conjugated bilirubin in the blood. This is caused by a defect in secretion of bilirubin glucuronides (already conjugated) across the canalicular membrane (patients are missing a canalicular protein that transports bilirubin glucuronides into bile). The protein was originally termed the canalicular multiple organic anion transporter ( cMOAT ) but is also known as multidrug resistance protein 2 (MRP2). 3/1/2018 Rajendra Dev Bhatt

31. Congenital conditions that may cause jaundice 3.Rotor’s syndrome: Is another autosomal recessive disorder in which patients have an increase in conjugated bilirubin in the blood. The exact molecular defect is unknown – but it seems these patients have multiple defects in hepatocyte uptake and excretion of bilirubin pigments. The liver looks normal, and as in Dubin -Johnson syndrome, most patients are asymptomatic. 3/1/2018 Rajendra Dev Bhatt

32. Congenital conditions that may cause jaundice 4. Gilbert syndrome: This syndrome is common which is estimated around 5-10% of the population has it. In this disorder, patients have a decreased activity of UGT1A1. It sounds just like type II CNS. However, Gilbert syndrome (which is an autosomal recessive syndrome) has a UGT1A1 activity level of about 30% of normal, which is quite a bit higher than the amount of activity we see in CNS. Patients usually have only mild Unconjugated hyperbilirubinemia. 3/1/2018 Rajendra Dev Bhatt

33. Physiological Neonatal Jaundice Most infants (around 60%) develop visible jaundice due to elevation of unconjugated bilirubin concentration during their first week. This common condition is called Physiological Neonatal Jaundice. Bilirubin produced by the fetus is cleared by the placenta and eliminated by the maternal liver. Immediately after birth, the neonatal liver must assume responsibility for bilirubin clearance and excretion. However, many hepatic physiologic processes are incompletely developed at birth. 3/1/2018 Rajendra Dev Bhatt

34. MECHANISM OF NEONATAL JAUNDICE 1.More bilirubin produced Destruction of HbF Shorter life span of fetal red blood cells 2.The low capability of albumin on unconjugated bilirubin transportation 3.The low capability of hepatocytes 4.High workload of the hepato-enteric circulation Less bacterial (low conversion of bilirubin to urobilinogen by the intestinal flora) Low enzymatic activity in intestine 3/1/2018 Rajendra Dev Bhatt

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37. The liver is the largest organ in the body. It is located below the diaphragm in the right upper quadrant of the abdominal cavity and extended approximately from the right 5 th rib to the lower border of the rib cage. The working cells of the liver are known as hepatocytes . The Liver 3/1/2018 Rajendra Dev Bhatt

38. Functions of Liver Synthetic function Synthesis of plasma proteins (albumin, coagulation factors, many globulins) Synthesis of cholesterol Synthesis of Triacylglycerol Lipoprotein synthesis 3/1/2018 Rajendra Dev Bhatt

39. Functions of Liver 2. Metabolic function Carbohydrates : Glycolysis ; glycogen synthesis; glycogen breakdown; Gluconeogenesis Ketogenesis ; fatty acid synthesis and breakdown Protein catabolism Citric acid cycle, production of ATP 3/1/2018 Rajendra Dev Bhatt

40. Functions of Liver 3. Detoxification and excretion a. Ammonia to urea b. Bilirubin (bile pigment) c. Cholesterol d. Drug metabolites 3/1/2018 Rajendra Dev Bhatt

41. Functions of Liver 4 . Homeostasis: Blood glucose regulation 5. Storage function : Vitamin A, D, K, B12 6. Production of bile salts; help in digestion 3/1/2018 Rajendra Dev Bhatt

42. Liver Function Tests (LFT) Biochemical tests are of immense value in diagnosis and monitoring of liver diseases. These tests are usually referred to as “liver function tests” (LFT). LFTs are the most widely performed biochemical tests in the laboratory. Number of tests are required to assess hepatic function All the tests n e ed no t b e p e r f orm e d in every patient The tes t s sho u l d b e select e d acc o rdi n g to the clinical symptoms and signs Liver function tests are performed usually to Detect hepatocellular damage Evaluate the functional status of liver Distinguish between different types of jaundice 3/1/2018 Rajendra Dev Bhatt

43. Liver Function Tests (LFT) Indications for Liver Function Tests 1 . Jaundice 2. Suspected liver metastasis 3. Alcoholic liver disease 4. Any undiagnosed chronic illness 5. Annual check up of diabetic patients 6. Coagulation disorders 7. Therapy with statins to check hepatotoxicity 3/1/2018 Rajendra Dev Bhatt

44. Liver Function tests Based on Laboratory Findings Group I (Tests of hepatic excretory function ) i . Serum Bilirubin ; total, conjugated, & unconjugated ii. Urine Bile pigments, bile salts and urobilinogen Group II: Liver enzyme panel (markers of liver injury/cholestasis) i . Alanine amino transferase ( ALT/SGPT) ii. Aspartate amino transferase ( AST/SGOT) iii. Alkaline phosphatase (ALP) iv. Gamma glutamyl transferase (GGT ) 3/1/2018 Rajendra Dev Bhatt

45. Liver Function tests Based on Laboratory Findings Group III: Plasma proteins ( synthetic function) i . Total proteins ii . Serum albumin, globulins, A/G ratio iii . Prothrombin time Group IV: Special tests Ceruloplasmin Ferritin Alpha-1-antitrypsin Alpha-fetoprotein 3/1/2018 Rajendra Dev Bhatt

46. Liver Function tests Cont… Measurement of total, unconjugated and conjugated bilirubin in serum helps in : Detection of jaundice and differentiate types of jaundice In haemolytic jaundice, total and unconjugated bilirubin are raised In hepatocellular jaundice,total,unconjugated and conjugated bilirubin are raised I n o b structive j a u n d ice, to t al and conj u gated bilirubin are raised 3/1/2018 Rajendra Dev Bhatt

47. Liver Function tests Cont… Bilirubin is the major bile pigment in human beings Normally, it is not present in urine Only c o n j uga t ed b i lirub i n i s sol u b l e in water , and can be excreted in urine Con j u g ated bi l iru b in i n serum i s raised in hepatocellular and obstructive jaundice T h er e f o re, bilirub i n i s prese n t in ur i ne in hepatocellular and obstructive jaundice Bile pigments in urine 3/1/2018 Rajendra Dev Bhatt

48. Liver Function tests Cont… Urobilinogen in urine Urobilinogen is formed from bilirubin in the intestine It is absorbed into portal circulation, and is mostly re-excreted by the liver in bile Some of it escapes from liver into systemic circulation, and is excreted in urine Normal urine contains a very small amount of urobilinogen 3/1/2018 Rajendra Dev Bhatt

49. Liver Function tests Cont… In haemolytic jaundice,formation of bilirubin is increased Hence, there is increased formation of urobilinogen Consequently, urinary urobilinogen is increased In obstructive jaundice, bilirubin doesn’t reach the intestine Hence, no urobilinogen is formed in the intestine Therefore , no urobilinogen is present in urine In hepatocellular jaundice , urinary urobilinogen is : Normal 3/1/2018 Rajendra Dev Bhatt

50. Liver Function tests Cont… Bile salts in urine Bile salts are formed in the liver from cholesterol They are excreted in bile In obstructive j a u n dice, bi l e sal t s can n ot reach intestine due to biliary obstruction They are regurgitated from liver into systemic circulation Since they are water-soluble, they are excreted in urine 3/1/2018 Rajendra Dev Bhatt

51. Liver Function tests Cont… In hepatocellular jaundice, swollen liver cells compress biliary canaliculi Hence, there is intrahepatic obstruction of biliary canaliculi Bile salts cannot reach intestine , and appear in urine In haemolytic jaundice, there is no obstruction to the flow of bile therefore , bile salts are not present in urine 3/1/2018 Rajendra Dev Bhatt

52. Liver Function tests Cont… H a em o lytic jaundice Hepatic jau n di c e Ob s tructive jaundice Serum bilirubin (total) Raised Raised Raised Serum bilirubin (un c o n jug a ted) Raised Raised Normal Serum bilirubin (conjugated ) Normal Raised Raised Bile pigments in urine Absent Present Present Urobilinogen in urine Raised Normal Absent Bile salts in urine Absent Present Present 3/1/2018 Rajendra Dev Bhatt

53. Liver Function tests Cont… Serum proteins and albumin : globulin ratio Liver is the only site of albumin synthesis Albumin synthesis decreases in liver disease Hence, serum albumin is level is decreased Glo b ul i n synt h esis ma y be increased specially in infective diseases 3/1/2018 Rajendra Dev Bhatt

54. Liver Function tests Cont… Serum enzymes I n viral h e p a t i tis, t h ere acute necrosis of liver cells Enzym e s pr e s e nt i n hep a tic cells are released in blood This ra i ses t h e concentr a tion of several enzymes in serum The rise in serum GPT is generally greater than that in GOT in liver disease Serum -glutamyl transpeptidase (GGT) is increased in many liver diseases Rise in serum GGT is a sensitive indicator of alcoholic hepatitis 5 ’ - Nucleo t idase i s also raised i n many liver diseases 3/1/2018 Rajendra Dev Bhatt

55. Liver Function tests Cont… Alkaline phosphatase (ALP) is synthesized in liver, bones, intestine and placenta In liver, ALP is synthesized by paren - chymal cells as well as epithelial cells of biliary canaliculi Serum ALP is mildly raised in viral hepatitis due to necrosis of parenchymal cells A marked elevation in serum ALP occurs in obstructive jaundice 3/1/2018 Rajendra Dev Bhatt

56. Liver Function tests Cont… Prothrombin time Prothrombin is synthesized in liver Prothrombin synthesis is decreased in hepato-cellular disease This leads to a decrease in prothrombin concentration in plasma which prolongs prothrombin time Pr o t h romb i n time i s pr o l o n g ed in vitamin K deficiency also. ( Newly-synthesized prothrombin is inactive, V it a min K i s re q uired for the post - translational modification) 3/1/2018 Rajendra Dev Bhatt

57. Liver Function tests Cont… Special Tests Ceruloplasmin: A globulin protein which transports copper. This test is used to aid in the diagnosis of Wilson’s disease, a hereditary syndrome in which decreased levels of ceruloplasmin are manufactured by the liver . Without ceruloplasmin to transport it, copper accumulates in the tissues of the brain , eye, kidney, and liver. One of the hallmarks of this disease is the presence of copper deposits around the iris of the eye, known as Kayser -Fleischer rings. 3/1/2018 Rajendra Dev Bhatt

58. Liver Function tests Cont… Ferritin : Ferritin is the primary protein in the body which stores iron. Thus, measurement of the ferritin level provides a good indication of the size of the body’s available iron stores . The ferritin level decreases before symptoms of anemia occur. For example , in Stage 1 of iron deficiency anemia, ferritin , and hemosiderin stores are depleted . Level of Ferritin increased in acute hepatitis and inflammatory disease. 3/1/2018 Rajendra Dev Bhatt

59. Liver Function tests Cont… Alpha-1-antitrypsin : Is a single polypeptide chain having 394 amino acids, also known as α1- antiproteinase . It increases during: Inflammation- an acute phase protein Chronic hepatocellular diseases Biliary tract obstruction And it decreases in: Nephrotic syndrome Emphysema Liver cirrhosis 3/1/2018 Rajendra Dev Bhatt

60. Liver Function tests Cont… Alpha-fetoprotein: Alpha-fetoprotein (AFP) is a globulin protein formed in the yolk sac and liver of the fetus . As the fetus develops, the level of AFP found in the mother’s serum increases . Only minute amounts of AFP remain in the bloodstream after birth . AFP is also considered a tumor marker for several types of cancer. Cancers typically are characterized by undifferentiated cells . The higher the AFP level, the greater amount of tumor present. Thus, AFP can also be used to assess response to cancer treatment . 3/1/2018 Rajendra Dev Bhatt

61. Some Uncommon L iver Function T ests Galactose tolerance test: Liver converts the dietary g a lact o se into glucose Capacity of liver to convert galactose into glucose is decreased in liver disease Hence, blood galactose remains elevated for a long time after ingestion of galactose Oral galactose tolerance test is preferable, and is done after an overnight fast Forty gm of galactose, dissolved in water is given by mouth to the subject Bl o od galact o se i s m e asur e d 60 minutes later A bl o od g a lactose level a b ove 6 0 m g /dl indicates impairment of hepatic function 3/1/2018 Rajendra Dev Bhatt

62. Some Uncommon L iver Function T ests Hippuric acid test: T h is i s a t e st o f con j uga t i n g functi o n of liver Benzoic acid is given to the subject Liver conjugates benzoic acid with Glycine to form Hippuric acid Hippuric acid is excreted in urine I f liver fu n ction i s n o rma l , all the b e nzoic acid is conjugated to form Hippuric acid All the Hippuric acid is excreted in urine If liver function is impaired, formation and excretion of Hippuric acid is decreased 3/1/2018 Rajendra Dev Bhatt

63. Some Uncommon L iver Function T ests Immunological tests: Detection of anti-mitochondrial antibody helps in the diagnosis of primary biliary cirrhosis. Detection of anti-nuclear and/or anti- smooth muscle antibodies helps in the diagnosis of autoimmune hepatitis. 3/1/2018 Rajendra Dev Bhatt

64. Some Uncommon L iver Function T ests Blood ammonia: In advanced liver disease, liver may fail to convert ammonia into urea This can cause hepatic encephalopathy Measurement of blood ammonia helps in its diagnosis and monitoring. 3/1/2018 Rajendra Dev Bhatt

65. Thank You 3/1/2018 Rajendra Dev Bhatt