Bilirubin and Liver

A 22-year-old medical student develops jaundice only when he stays up all night studying. His physical examination is normal. All hepatitis serologic tests are negative. What are his expected laboratory findings?

%CB: <20 Urine Bilirubin: NEGative Urine UBG: Normal AST: Normal ALT: Normal ALP: Normal GGT: Normal The patient has Gilbert's disease, which is an autosomal dominant disease characterized by decreased uptake and conjugation of bilirubin particularly exacerbated by the fasting state. Baseline UCB levels are increased to over twice normal in the fasting state leading to visible evidence of jaundice (CB<20%). Next to viral hepatitis, it is the second overall most common cause of jaundice in the United States. It has no clinical significance

Reye's syndrome discussion

-primarily occurs in children with viral infections (varicella,influenza) and exposure to salicylates -Salicylates damage hepatocytes: produces diffuse fatty change (increase transaminases) and disrupts the urea cycle (increases serum ammonia)

Reye's syndrome (RS)

1) This acute disorder of young children is characterized by encephalopathy, coma, and microvesicular fatty liver 2) associated with aspirin administration to children with acute viral infections 3)associated with the presence of small fat vacuoles in parenchymal liver cells

Bilirubin is transported from reticuloendothelial cells to the liver by: a) Albumin b) Bilirubin-binding globulin c) Haptoglobin d) Transferrin

A) Albumin Albumin transports bilirubin, haptoglobin transports free Hgb, and transferrin transports ferric iron. When albumin binding is exceeded, unbound bilirubin, called free bilirubin, increases. This may cross the blood-brain barrier, resulting in kernicterus

A 20-year-old man presents with yellowing of the sclerae, skin, and oral mucosa. Which of the following accumulations underlies these findings? a) Bilirubin b) Hemosiderin c) Lead d) Melanin e) Silver

A) Bilirubin Yellowing of the sclerae,skin, and oral mucosa are all characteristic of jaundice, the accumulation of bilirubin, the catabolic product of the heme moiety of hemoglobin. Jaundice can occur by diverse mechanisms: hemolytic, hepatocellular, or obstructive

A neonate has been persistently jaundiced from birth despite aggressive phototherapy and exchange transfusions. Laboratory studies demonstrate significantly elevated unconjugated bilirubin. Tests from an outside laboratory confirm the total absence of glucuronyl transferase activity. The neonate most likely has which of the following conditions? a) Crigler-Najjar syndrome b) Gilbert syndrome c) Hemolytic disease of the newborn d) Physicologic jaundic of the newborn e) Rotor syndrome

A) Crigler-Najjar syndrome A total lack of glucuronyl transferase results in Crigler-Najjar syndrome I, which is invariably fatal after 18 months secondary to kernicterus

Which of the following would cause an increase in only the unconjugated bilirubin? a) Hemolytic anemia b) Obstructive jaundice c) Hepatitis d) Hepatic cirrhosis

A) Hemolytic anemia Conjugated bilirubin increases as a result of obstructive processes within the liver or biliary system or from failure of the enterohepatic circulation. Hemolytic anemia (prehepatic jaundice) presents a greater bilirubin load to a normal liver, resulting in increased bilirubin excretion. When the rate of bilirubin formation exceeds the rate of excretion, the unconjugated bilirubin rises.

Which of the following statements regarding urobilinogen is true? a) It is formed in the intestines by bacterial reduction of bilirubin b) It consists of a single water-soluble bile pigment c) It is measured by its reaction with p-aminosalicylate d) In hemolytic anemia, it is decreased in urine and feces

A) It is formed in the intestines by bacterial reduction of bilirubin Urobilinogen is a collective term given to the reduction products of bilirubin formed by the action of enteric bacteria. Urobilinogen excretion is increased in extravascular hemolytic anemias and decreased in obstructive jaundice (cholestatic disease). Urobilinogen is measured using Ehrlich's reagent, an acid solution of p-dimethylaminobenzaldehyde.

Which statement regarding total and direct bilirubin levels is true? A) Total bilirubin level is a less sensitive and specific marker of liver disease than the direct level B) Direct bilirubin exceeds 3.5mg/dL in most cases of hemolytic anemia C) Direct bilirubin is normal in cholestatic liver disease D) The ratio of direct to total bilirubin exceeds 0.40 in hemolytic anemia

A) Total bilirubin level is a less sensitive and specific marker of liver disease than the direct level Direct bilirubin measurement is a sensitive and specific marker for hepatic an posthepatic jaundice because it is not elevated by hemolytic anemia. In hemolytic anemia, the total bilirubin does not exceed 3.5mg/dL, and the ratio of direct to total is less than 0.20. Unconjugated bilirubin is the major fraction in necrotic liver disease because microsomal enzymes are lost. Unconjugated bilirubin is elevated along with direct bilirubin in cholestasis because some necrosis takes place and some conjugated bilirubin is hydrolyzed back to unconjugated bilirubin

In the Jendrassik-Grof method for the determination of serum bilirubin concentration, quantitiation is obtained by measuring the green color of: a) azobilirubin b) bilirubin glucuronide c) urobilin d) urobilinogen

A) azobilirubin In the Jendrassik-Grof method for bilirubin measurement, the addition of caffeine plus diazotized sulfanilic acid and the serum produces azobilirubin. Ascorbic acid, alkaline tartrate, and dilute HCl are added to the reaction mixture to stabilize and create the azobilirubin. The blue-green azobilirubin is measured. Bilirubin glucuronide, urobilin, and urobilinogen are intermediaries of bilirubin metabolism. They are not measured by this method. [Tietz 2015, p518]

In which of the following disease states is conjugated bilirubin a major serum component? a) biliary obstruction b) hemolysis c) neonatal jaundice d) erythroblastosis fetalis

A) biliary obstruction Intrahepatic biliary atresia in the newborn can also cause conjugated hyperbilirubinemia while in the adult it is likely due to biliary obstruction or hepatitis. [Tietz 2015, p516]

A 13-year-old boy presents to the pediatrician with extrapyramidal signs, including a resting and kinetic tremor. An ophthalmologic examination demonstrates the presence of Kayser-Fleischer rings, and his laboratory studies demonstarte elevated liver enzymes. It is likely that the patient's condition is associated with the accumulation of: a) copper b) Councilman bodies c) eosinophilic hyaline inclusions d) glycogen e) iron

A) copper Wilson disease is a hereditary condition associated with the accumulation of copper in the liver, brain, and eye. Accumulation of copper in the Descemet membrane of the eye results in pathognomonic lesion known as the Kayser-Fleischer ring. Accumulation in the liver results in cirrhosis. Accumulation in the brain, specifically in the basal ganglia, results in motor symptoms. Councilman bodies are apoptic hepatocytes that were first identified in yellow fever. Eosinophilic hyaline inclusions, Mallory Bodies, are seen in alcoholic liver disease. Glycogen accumulates in the liver in numerous glycogen storage diseases. Iron accumulates in hemochromatosis

Alcoholic Hepatitis labs

AST>ALT AST is primarily located in the mitochondria and alcohol damages mitochondria

Pathogenesis of hepatic steatosis.

An increased uptake and/or decreased disposal of lipids (fatty acids) in the liver results in an accumulation of fat within hepatocytes. (FFA, free fatty acid; NEFA, non-esterified fatty acid; VLDL, very-low-density lipoprotein.) (Redrawn, with permission, from Machado MV et al. Pathogenesis of nonalcoholic steatohepatitis. Gastroenterology. 2016 Jun;150(8):1769-77. Copyright © Elsevier.)

In hepatitis, the rise in serum conjugated bilirubin can be caused by: a) Secondary renal insufficiency b) Failure of the enterohepatic circulation c) Enzymatic conversion of urobilinogen to bilirubin d) Extrahepatic conjugation

B) Failure of the enterohepatic circulation Conjugated bilirubin is increased in hepatitis and other causes of hepatic necrosis due to failure to re-excrete conjugated bilirubin reabsorbed from the intestine. Increased direct bilirubin can also be attributed to accompanying intrahepatic obstruction, which blocks the flow of bile.

Which statement best characterizes serum bilirubin levels in the first week following delivery? a) Serum bilirubin 24 hours after delivery should not exceed the upper reference limit for adults b) Jaundice is usually first seen 48-72 hours postpartum in neonatal hyperbilirubinemia c) Serum bilirubin above 5.0mg/dL occuring 2-5 days after delivery indicates hemolytic or hepatic disease d) Conjugated bilirubin accounts for about 50% of the total bilirubin in neonates

B) Jaundice is usually first seen 48-72 hours postpartum in neonatal hyperbilirubinemia Bilirubin levels may reach as high as 2-3mg/dL in the first 24 hours after birth owing to the trauma of delivery, such as resorption of a subdural hematoma. Neonatal hyperbilirubinemia occurs 2-3 days after birth due to increased hemolysis at birth and transient deficiency of the microsomal enzyme, UDP-glucuronyl transferase. Normally levels rise to about 5-10mg/dL, requiring therapy with UV light to photo-oxidized the bilirubin. Neonatal jaundice can last up to 1 week in a mature neonate and up to 2 weeks in premature babies. Neonatal bilirubin is almost exclusively unconjugated.

A 35-year-old male has a 10 year history of alcohol abuse. Physical examination reveals physical examination reveals tender hepatomegaly. A CBC shows macrocytosis without anemia. Round macrocytes, many of which have a target cell appearance, are present in the peripheral blood. No hyper segmented neutrophils are noted. Liver studies show a slight increase in serum aspartame aminotransferase (AST).. What is the most likely diagnosis? A) Anemia of Chronic Disease B) Nonmegaloblastic macrocytosis C) Aplastic Anemia D) Warm Autoimmune Hemolytic Anemia

B) Nonmegaloblastic macrocytosis Macrocytosis associated with alcohol may be due folate deficiency(most common; anemia present), liver disease (no anemia) or a direct toxic effect of alcohol (anemia). In this patient the macrocytosis is due to liver disease, most likely fatty change. Because of alcohol is mitochondrial toxin, AST located in the mitochondria is preferentially released into the blood over alanine aminotransferase, which is located in the cytosol. The patient has a nonmegaloblastic type of macrocytosis, because there are no hypersegmented neutrophils adn the macrocytic cells are round and often show target cell formation. Target cells have an excess of RBC membrane due to an increase in the cholesterol content in the membrane. Folate deficiency produces a megaloblastic type of macrocytic anemia due to diminished DNA synthesis. There is typically pancytopenia with macroovalocytes and hypersegmented neutrophils. (Goljan Clinical Lab Review; p203)

The treatment of persons with hepatic encephalopathy, which one of the following decreases ammonia absorption? A) sucrose B) lactulose C) protein D) glucose E) galactose

B) lactulose Lactulose, a non-absorbable disaccharide, acts as an osmotic laxative. It works to decrease ammonia absorption. The other sugars and protein are not indicated in the treatment of hepatic encephalopathy. (Braunwald 15/e, pp1765-1766)

Which form of hyperbilirubinemia is caused by an inherited absence of UDP-glucuronyl transferase? a) Gilbert's syndrome b) Rotor syndrome c) Crigler-Najjar syndrome d) Dubin-Johnson syndrome

C) Crigler-Najjar syndrome Crigler-Najjar syndrome is a rare condition that occurs in two forms. Type 1 is inherited as an autosomal recessive trait and causes a total deficiency of UDP-glucoronyl transferase. Life expectancy is less than 1 year. Type 2 is an autosomal dominant trait and is characterized by lesser jaundice and usually the absence of kernicterus. Bilirubin levels can be controlled with phenobarbital, which promotes bilirubin excretion. Gilbert's syndrome is an autosomal recessive condition characterized by decreased bilirubin uptake and decreased formation of bilirubin diglucoronide. It is the most common inherited form of jaundice. Dubin-Johnson and Rotor syndromes are autosomal recessive disorders associated with defective delivery of bilirubin into the biliary system.

Which condition is caused by deficient secretion of bilirubin into the bile canaliculi? a) Gilbert's disease b) Neonatal hyperbilirubinemia c) Dubin-Johnson syndrome d) Crigler-Najjar syndrome

C) Dubin-Johnson syndrome Dubin-Johnson syndrome is an autosomal recessive condition arising from mutation of an ABC transporter gene. It produces mild jaundice from accumulation of conjugated bilirubin that is not secreted into the bile canaliculi. Total and direct bilirubin are elevated, but other liver function is normal. Rotor syndrome is an autosomal recessive condition that also results in retention of conjugated bilirubin. The mechanism is unknown, and like Dubin-Johnson syndrome it is commonly asymptomatic. It can be differentiated from Dubin-Johnson syndrome by the pattern of urinary coproporphyrin excretion and because it produces no black pigmentation in the liver.

The most sensitive enzymatic indicator for liver damage from ethanol intake is: a) ALT b) AST c) GGT d) ALP

C) GGT GGT levels are elevated in alcoholism. The levels may range from 2-3 times the upper limit of normal. ALT, AST, and ALP may be increased depending on the alcohol damage to the liver [Bishop 2018, p279]

Which one of the following disorders of bilirubin metabolism shows increased unconjugated bilirubin, increased conjugated bilirubin, and positive bilirubin in the urine? A) neonatal jaundice B) Crigler-Njjar syndrome, types I and II C) Hepatitis D) Gilbert's syndrome E) Ineffective erythropoiesis

C) Hepatitis This case shows the laboratory findings inhepatitis. In Crigler-Najjar syndrome and neonatal jaundice, the conjugated bilirubin is low and no bilirubin is found in the urine. In Gilbert's syndrome and ineffective erythropoiesis , the conjugated bilirubin is low and normal, respectively, and no bilirubin is found in the urine.

Biochemical profile: Total protein: 7.3g/dL (6.0-8.0g/dL) Albumin: 4.1g/dL (3.5-5.0g/dL) Calcium: 9.6mg/dL (8.5-10.5mg/dL) Phosphorous: 3.3mg/dL (2.5-4.5mg/dL) Glucose: 95mg/dL (65-110mg/dL) BUN: 16mg/dL (10-20mg/dL) Uric acid: 6.0mg/dL (2.5-8.0mg/dL) Creatinine: 1.2mg/dL (0.7-1.4mg/dL) ALP: 275 U/L (30-80 U/L) Total Bilirubin: 3.7mg/dL (0.2-0.9mg/dL) Lactate dehydrogenase: 185 U/L (100-225 U/L) AST: 75 U/L (10-40 U/L) The results of this biochemical profile are most consistent with: a) viral hepatitis b) hemolytic anemia c) common bile duct stones d) chronic active hepatitis

C) common bile duct stones Conjugated hyperbilirubinemia with elevated alkaline phosphatase is associated with cholestatic-hepatic biliary obstruction; increased alkaline phosphatase more so than AST [Tietz 2015, p720-721]

Which is the most common precipitating event of hepatic encephalopathy? A) constipation B) hyperkalemia C) gastrointestinal bleeding D) hypernatremia E) acidosis

C) gastrointestinal bleeding gastrointestinal bleeding is the single most important precipitating event of hepatic encephalopathy. It leads to an increase in ammonia and other nitrogenous substances that are absorbed. Other factors that can precipitate hepatic encephalopathy include hyperkalemia, hypernatremia, and constipation; however, constipation is a much less important precipitating event than G.I. bleeding

What substance gives feces its normal color? a) uroethryin b) urochrome c) urobilin d) urobilinogen

C) urobilin (really stercobilin) Bile pigments (uro-, meso-, stercobilin) are found in feces. The precursors are urobilinogens which are oxidized to form the bile pigments. [Tietz 2015, p515]

________________ bilirubin is filtered at the glomerulus, and the majority is reabsorbed by the proximal tubules; a small fraction is excreted in the urine. Any bilirubin found in the urine is _____________ bilirubin.

Conjugated

Obstructive Jaundice

Conjugated Hyperbilirubinemia Hyperbilirubinuria Decreased Urine Urobilinogen ALP and Cholesterol Increased Complete obstruction: stools pale and clay-colored

Hepatocellular Jaundice

Conjugated Hyperbilirubinemia Unconjugated Hyperbilirubinemia Hyperbilirubinuria Normal Urine Urobilinogen AST and ALT increased Increased ALP indicates intrahepatic obstruction

In the liver, bilirubin is conjugated by addition of: a) Vinyl groups b) Methyl groups c) Hydroxyl groups d) Glucoronyl groups

D) Glucoronyl groups The esterificiation of glucoronic acid to the propionyl side chains of the inner pyrrole rings (I and II) makes bilirubin water soluble. Conjugation is required before bilirubin can be excreted via the bile.

The most widely used methods for bilirubin measurement are those based on the: a) Jaffe reaction b) Schales and Schales method c) 8-hydroxyquinoline method d) Jendrassik-Grof method

D) Jendrassik-Grof method Jendrassik-Grof is the modified Malloy and Eveyln method and is most commonly used as bilirubin methods. The Jaffe reaction is used in creatinine analysis and Schales and Schales is a classic chloride method while 8 hydroxyquinoline is used in the CPC method of calcium to remove interference of Mg2+ [Tietz 2015, p517]

A -65-year-old Caucasian male physician comes in for his annual physical examination and is noted to have palmar erythema, tremors, and a prominent abdomen with exaggerated superficial veins. Upon gentle inquiry, he admits to having three to four beers a night for most of his career except when on call, and discloses that his father died from cirrhosis. His family practicioner obtains a hepatic function panel that includes: a serum aspartate aminotransferase level (AST also known as SGOT) of 350 U/L (normal 15-45 U/L); and serum alanine aminotransferase (ALT also known as SGPT) of 280 U/L (normal 10-40 U/L). Which of the following best conveys the role transaminases like AST and ALT and the significance of their serum elevations? A) produce alpha-ketoglutarate, inhibit gluconeogenesis, reveal liver cell death B) produce glutamate, promote gluconeogenesis, reveal liver cancer C) Produced urea, inhibit gluconeogenesis, reveal liver cancer D) Remove ammonia, promote gluconeogenesis, reveal liver cell death E) Remove ammonia, inhibit gluconeogenesis, reveal liver cancer

D) Remove ammonia, promote gluconeogenesis, reveal liver cell death Enzymes specific for a few tissues can reveal injury to that tissue by leakage into the bloodstream, illustrated by increased serum aspartate aminotransferase level (AST also known as SGOT) and serum alanine aminotransferase (ALT also known as SGPT) in liver dieases (hepatitis, alcoholic cirrhosis) that destroy hepatic tissue Cancers derived from normal tissues (e.g., hepatocarcinoma from hepatic cellss) usually have their own marker proteins (e.g., alpha-fetoprotein for hepatocarcinoma---the liver cancer portion makes answers b,c,e incorrect). Aminotransferases have several roles including control of toxic ammonium ion (NH4+); they transfer the amino groups of amino acids to alpha-ketoglutarate and then to glutamate, followed by oxidative deamination to produce ammonium ion. The ammonium ion can enter the urea cycle to form urea or be excreted to balance acidosis (the first parts of answers a-e are all correct). Several transamination reactions (e.g. alanine to pyruvate) provide substrates for gluconeogenesis (middle parts of a,c,e incorrect) and most are reversible and able to provide amino acids for protein synthesis

In the Malloy and Evelyn method for the determination of bilirubin, the reagent that is reacted with bilirubin to form a purple azobilirubin is: a) dilute sulfuric acid b) diazonium sulfate c) sulfobromophthalein d) diazotized sulfanilic acid

D) diazotized sulfanilic acid The diazo method of Malloy and Evelyn involves bilirugin reacting with diazotized sulfanilic acid to form azobilirubin [Bishop 2018, p514]

DECREASED HEPATIC BILIRUBIN CLEARANCE

Decreased Hepatic Uptake Decreased hepatic bilirubin uptake is believed to contribute to the unconjugated hyperbilirubinemia of Gilbert's syndrome (GS), although the molecular basis for this finding remains unclear (see below). Several drugs, including flavaspidic acid, novobiocin, and rifampin, as well as various cholecystographic contrast agents, have been reported to inhibit bilirubin uptake. The resulting unconjugated hyperbilirubinemia resolves with cessation of the medication.

Which one of these drugs is of proven benefit in the treatment of persons with hepatic encephalopathy? A) levodopa B) bromocriptine C) Keto analogues of essential amino acids D) branched-chain amino acids E) tetracycline

E) tetracycline In addition to lactulose, antibiotics decrease ammonia production by intestinal bacteria. Tetracycline is effective, as our ampicillin and metronidazole. Neomycin is effective, but but it is absorbed some and can cause renal toxicity. The role of the other drugs in the treatment of hepatic encephalopathy is unproven. (Braunwald 15/e, pp1765)

Albumin-bound bilirubin in sinusoidal blood passes through endothelial cell fenestrae to reach the hepatocyte surface, entering the cell by both facilitated and simple diffusional processes. Within the cell, it is bound to glutathione-S-transferases and conjugated by bilirubin-UDP-glucuronosyltransferase (UGT1A1) to mono- and diglucuronides, which are actively transported across the canalicular membrane into the bile. In addition to this direct excretion of bilirubin glucuronides, a portion are transported into the portal circulation by MRP3 and subjected to reuptake into the hepatocyte by OATP1B1 and OATP1B3. ALB, albumin; BDG, bilirubin diglucuronide; BMG, bilirubin monoglucuronide; BT, proposed bilirubin transporter; GST, glutathione-S-transferase; MRP2 and MRP3, multidrug resistance-associated proteins 2 and 3; OATP1B1 and OATP1B3, organic anion transport proteins 1B1 and 1B3; UCB, unconjugated bilirubin; UGT1A1, bilirubin-UDP-glucuronosyltransferase.

Hepatocellular bilirubin transport

Site for a tumor that could potentially produce hypoglycemia and secondary polycythemia

Liver A hepatocellular carcinoma can produce an insulin-like factor producing hypoglycemia or EPO producing secondary polycythemia

Increased Serum GGT

Obstructive jaundice (intra- and extrahepatic types)

refers to events in the biliary tree, for which the major causes are obstruction of the common bile duct by a gallstone (biliary calculus) or by cancer of the head of the pancreas.

Posthepatic jaundice

Jaundice is first notice where?

Sclerae

Why Sclerae?

Sclerae have a particular affinity for bilirubin due to their high elastin content, and the presence of scleral icterus indicates a serum bilirubin level of at least 51 μmol/L (3 mg/dL)

Bilirubin secretion.

This water-insoluble compound is derived from the metabolism of hemoglobin in macrophages of the mononuclear phagocyte system. Glucuronyl transferase activity in the hepatocytes causes bilirubin to be conjugated with glucuronide in the smooth endoplasmic reticulum, forming a water-soluble compound. An accumulation of bilirubin and bilirubin glucuronide in the tissues produces jaundice. Several defective processes in the hepatocytes can cause diseases that produce jaundice: a defect in the capacity of the cell to trap and absorb bilirubin (rectangle 1), the inability of the cell to conjugate bilirubin because of a deficiency in glucuronyl transferase (rectangle 2), or problems in the transfer and excretion of bilirubin glucuronide into the biliary canaliculi (rectangle 3). One of the most frequent causes of jaundice, however—unrelated to hepatocyte activity—is the obstruction of bile flow as a result of gallstones or tumors of the pancreas. This causes jaundice primarily as a result of the accumulation of bilirubin glucuronide in the tissues. (Redrawn, with permission, from Junqueira LC et al, eds. Basic Histology, 10th ed. McGraw-Hill, 2003.)

_____________ bilirubin is always bound to albumin in the serum, is not filtered by the kidney, and is not found in the urine.

Unconjugated

Hemolytic Jaundice

Unconjugated Hyperbilirubinemia Urine Bilirubin Absent = Acholuria Urine Urobilinogen Increased Degree of urine uroblinogen increase directly related to increased hemoglobin catabolism

CB

Water soluble

In bilirubin determinations, the purpose of adding a concentrated caffeine solution or methyl alcohol is to: a) allow indirect bilirubin to react with color reagent b) dissolve conjugated bilirubin c) precipitate protein d) prevent any change in pH

a

Jaundice

a yellowish discoloration of body tissues resulting from the deposition of bilirubin

Which of the following is a characteristic of conjugated bilirubin? a) It is water soluble b) It reacts more slowly than unconjugated bilirubin c) It is more stable than unconjgated bilirubin d) It has the same absorbance properties as unconjugated bilirubin

a) It is water soluble Conjugated bilirubin refers to bilirubin mono- and diglucuronides. Conjugated bilirubin reacts almost immediately with the aqueos diazo reagent without need for a polar solvent. Historically, conjugated bilirubin has been used synonymously with direct-reacting bilirubin, although the latter includes the delta-bilirubin fraction when measured by the Jendrassik-Grof method. Conjugated bilirubin is excreted in both bile and urine. It is easily photo-oxidized and has very limited stability.

Wilson disease

accumulation of copper in liver, kidney, brain, and cornea; cirhosis can be macronodular; decreased serum ceruloplasmin

A low___________ level suggests a chronic process such as cirrhosis or cancer.

albumin

Hepatic jaundice

arises from hepatitis or other liver diseases (eg, cancer). results from an inability to take up, metabolize, or excrete bilirubin.

Kernicterus is an abnormal accumulation of bilirubin in: a) heart tissue b) brain tissue c) liver tissue d) kidney tissue

b

If the total bilirubin is 3.1 mg/dL (53.0umol/L) and the conjugated bilirubin is 2.0 mg/dL (34.2umol/L), the unconjugated bilirubin is: a) 0.5mg/dL (8.6umol/L) b) 1.1mg/dL (18.8umol/L) c) 2.2mg/dL (37.6umol/L) d) 5.1mg/dL (87.2umol/L)

b Total bilirubin = (direct) conjugated bilirubin + (indirect) unconjugated bilirubin

In the Jendrassik-Grof reaction for total bilirubin, alkaline tartrate is added to: a) form diazo bilirubin, a reddish chromogen b) eliminate many spectrophotometric interferences c) act as an accelerator d) react with delta-bilirubin

b) eliminate many spectrophotometric interferences Alkaline tartrate raises the pH and converts the azobilirubin from a reddish purple chromagen, with similar absorbances (450-560nm) as hemoglobin and other interfering substances to a bluish chromagen which absorbs at 600nm [Bishop 2018, p514]

To be transported in _____________ , bilirubin must be solubilized. Solubilization is accomplished by the reversible, noncovalent binding of bilirubin to albumin. Unconjugated bilirubin bound to albumin is transported to the liver. There, the bilirubin—but not the albumin—is taken up by hepatocytes via a process that at least partly involves carrier-mediated membrane transport.

blood

Alcoholic hepatitis

characteristics include fatty change, focal liver cell necrosis, infiltrates of neutrophils, and the presence of intracytoplasmic eosinophilic hyaline inclusions (Mallory bodies) derived from cytokeratin intermediate filaments; these inclusions are characteristic, but not entirely specific for _______ _________

Patients with a hepatocellular process generally have a rise in the aminotransferases that is disproportionate to that in ALP, whereas patients with a ______________ process have a rise in ALP that is disproportionate to that of the aminotransferases. The serum bilirubin can be prominently elevated in both hepatocellular and cholestatic conditions and therefore is not necessarily helpful in differentiating between the two.

cholestatic

Patients with a hepatocellular process generally have a rise in the aminotransferases that is disproportionate to that in ALP, whereas patients with a process have a rise in ALP that is disproportionate to that of the aminotransferases. The serum bilirubin can be prominently elevated in both hepatocellular and cholestatic conditions and therefore is not necessarily helpful in differentiating between the two.

cholestatic

Elevated ____________ hyperbilirubinemia is found in two rare inherited conditions: Dubin-Johnson syndrome and Rotor syndrome

conjugated

Hepatocytes take up free bilirubin from plasma and convert it to bilirubin diglucuronide via the enzyme glucuronyl transferase; this form of bilirubin is called ___________ (or direct) bilirubin and is water soluble

conjugated

Direct Bilirubin

conjugated bilirubin

In the liver, bilirubin is converted to: a) urobilinogen b) urobilin c) bilirubin-albumin complex d) bilirubin diglucuronide

d

Urobilinogen is formed in the: a) kidney b) spleen c) liver d) intestine

d

Before unconjugated bilirubin can react with Ehrlich diazo reagent, which of the following must be added? a) acetone b) ether c) distilled water d) caffeine

d) caffeine Caffeine is added to accelerate the reaction of unconjugated bilirubin to the diazo reagent. Ethanol, dyphylline and surfactants have also been used but no acetone or ether. [Tietz 2015, p518]

The _________ fraction is that which reacts with diazotized sulfanilic acid in the absence of an accelerator substance such as alcohol. The _________ fraction provides an approximation of the conjugated bilirubin level in serum.

direct

Dubin-Johnson syndrome is an autosomal recessive form of conjugated hyperbilirubinemia characterized by defective bilirubin transport. It is characterized by a striking brown-to-black _____________ of the liver caused by deposition of granules of very _________ pigment

discoloration dark

In the ____________ _________________, bilirubin is made aqueous soluble by conjugation to glucuronic acid, a process that disrupts the hydrophobic internal hydrogen bonds and yields bilirubin monoglucuronide and diglucuronide. The conjugation of glucuronic acid to bilirubin is catalyzed by bilirubin uridine diphosphate-glucuronosyl transferase (UDPGT). The now-hydrophilic bilirubin conjugates diffuse from the endoplasmic reticulum to the canalicular membrane,

endoplasmic reticulum

Physiologic jaundice of the newborn is commonly noted during the ________ week of life, but is not usually clinically important. It is characterized chemically by _______________ hyperbilirubinemia

first unconjugated

Patients with a ___________________ process generally have a rise in the aminotransferases that is disproportionate to that in ALP, whereas patients with a cholestatic process have a rise in ALP that is disproportionate to that of the aminotransferases. The serum bilirubin can be prominently elevated in both hepatocellular and cholestatic conditions and therefore is not necessarily helpful in differentiating between the two.

hepatocellular

Gamma Glutamyltransferase is located where?

in the smooth endoplasmic reticulum in hepatocytes

Prehepatic jaundice

indicates events in the bloodstream, major causes being various hemolytic anemias. is caused by conditions that present an excessive bilirubin load to the liver.

Bilirubin formed in the reticuloendothelial cells is virtually _______________ in water due to tight internal hydrogen bonding between the water-soluble moieties of bilirubin —that is, the bonding of the propionic acid carboxyl groups of one dipyrrolic half of the molecule with the imino and lactam groups of the opposite half. This configuration blocks solvent access to the polar residues of bilirubin and places the hydrophobic residues on the outside.

insoluble

Primary biliary cholangitis

is an autoimmune disease predominantly affecting middle-aged women and characterized by progressive destruction of interlobular bile ducts. The diagnosis is made by the detection of antimitochondrial antibody, which is found in 95% of patients. Primary sclerosing cholangitis is characterized by the destruction and fibrosis of larger bile ducts.

Urea cycle is present in the ______

liver

A _____________albumin level is suggestive of a more acute process such as viral hepatitis or choledocholithiasis.

normal

Urobilin

oxidation product of urobilinogen pigment responsible for yellow urine color

Alcoholic hepatitis can be differentiated from viral and toxin-related hepatitis by the pattern of the aminotransferases:

patients with alcoholic hepatitis typically have an AST-to-ALT ratio of at least 2:1, and the AST level rarely exceeds 300 U/L.

The formation of bilirubin occurs in __________________________ cells, primarily in the spleen and liver

reticuloendothelial

Bilirubin is released from macrophages and bound to albumin in the plasma because of its low solubility in water. This protein-bound form of bilirubin is referred to as ___________ (or indirect) bilirubin.

unconjugated

The indirect fraction is the difference between the total and the direct bilirubin levels and provides an estimate of the____________ bilirubin in serum.

unconjugated

Indirect Bilirubin

unconjugated bilirubin

Increased urinary excretion of _________________ can be due to increased bilirubin production, increased hepatic reabsorption of urobilinogen from the colon, or decreased hepatic clearance of urobilinogen.

urobilinogen

The unconjugated bilirubin is reduced by normal gut bacteria to form_________________ a group of colorless tetrapyrroles called and other products, the nature and relative amounts of which depend on the bacterial flora.

urobilinogens

Another sensitive indicator of increased serum bilirubin is darkening of the urine. What causes bilirubinuria?

which is due to the renal excretion of conjugated bilirubin. Patients often describe their urine as tea- or cola-colored. Bilirubinuria indicates an elevation of the direct serum bilirubin fraction and, therefore, the presence of liver or biliary disease.