Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Lab Med II > Hepatobiliary Tract and Pancreatic Enzymes > Flashcards

Hepatobiliary Tract and Pancreatic Enzymes Flashcards

1
Q

What is bilirubin?

A

yellow breakdown product of normal heme catabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Steps of bilirubin metabolism: Initial steps

A
  1. Old RBCs are phagocytized by macrophages of reticuloendothelial system (RES)
    In the spleen (mainly), liver and lymph nodes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Metabolism of bilirubin: Inside macrophages

A

1st - heme is converted to biliverdin by the enzyme heme oxygenase (HMOX)
2nd - biliverdin is converted to bilirubin by biliverdin reductase (BVR)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Metabolism of bilirubin: Transport to the liver

A

Unconjugated bilirubin (indirect bilirubin) is bound to albumin and is transported through the plasma into the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Metabolism of bilirubin: Inside the liver

A

Hepatocytes detach bilirubin from albumin to bring it inside the cell (uptake occurs via facilitated diffusion)
Bilirubin then conjugates with glucuronic acid to make conjugated bilirubin (direct bilirubin) → more water soluble

Conjugated bilirubin is excreted from the liver in the form of bile into the biliary system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Metabolism of bilirubin: Intestine

A

Once bile bilirubin(conjugated) is secreted into the intestine, intestinal bacteria convert to urobilinogens

Some urobilinogen is absorbed by intestinal cells and enters the portal blood

Some reabsorbed urobilinogen re-enters the bile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Metabolism of bilirubin: Reabsorbed and transported to the kidney

A

Some reabsorbed urobilinogen is transported by blood to the kidneys and is excreted in urine
Urobilin → product of oxidation of urobilinogen → responsible for the yellow color of urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Metabolism of bilirubin: Urobilinogen in the digestive tract

A

Remaining urobilinogen travels down the digestive tract and is converted to stercobilinogen
Oxidized to stercobilin, which is excreted and is responsible for the brown color of feces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Unconjugated or indirect bilirubin

A

Albumin-bound that is insoluble

Makes up most of the bilirubin in the blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Conjugated or direct bilirubin

post-hepatic

A

Water soluble form

Less common in the plasma but can occur from leaks in the hepatocytes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some possible causes of elevated serum bilirubin concentrations?

A
  1. Overproduction of bilirubin
  2. Impaired uptake, conjugation, or excretion of bilirubin
  3. Backward leakage of bilirubin from damaged hepatocytes or bile ducts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Reasons for increase in serum unconjugated bilirubin

A

Increased production (hemolysis)
Impaired uptake
Impaired conjugation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Reasons for increase in serum conjugated bilirubin

A 
Decreased excretion into bile ductules
Backward leakage (obstruction or blockage)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Unconjugated bilirubin lab value

A

Concentration is concentrated from total and direct bilirubin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Lab findings in prehepatic jaundice

A

Serum: Increased unconjugated bilirubin

Urine: No bilirubin present
Urobilinogen > 2 units (high)
Brown discolorations

Stool: Increased fecal urobilinogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Prehepatic (hemolytic) jaundice

A

Due to overproduction of bilirubin resulting from hemolytic processes that produce high levels of unconjugated bilirubin.

*Know what kinds of conditions can cause this. Slide 14

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Hepatocellular jaundice

A 
Results from injury or disease of the parenchymal cells of the liver and can be caused by (things that can caused by damage to liver cells):
Viral hepatitis
Cirrhosis
Infectious mononucleosis
Reactions to hepatotoxic medications
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Lab findings in hepatocellular jaundice

A

Serum: Increased total bilirubin, increased conjugated bilirubin, increased unconjugated bilirubin

Urine: Decreased urobilinogen
Increased conjugated bilirubin
Dark color

Stool: Pale color, decreased fecal urobilinogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Posthepatic of obstructive janudice

A

Usually the result of obstruction of the common bile duct or hepatic ducts due to gallstones or due to neoplasms (of the bile duct, gallbladder, or pancreas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Lab findings in posthepatic/ obstructive jaundice

A

Serum: Increased total bilirubin, increased conjugated bilirubin, normal unconjugated

Urine: Decreased or no urobilinogen, presence of conjugated bilirubin
Dark color

Stool: Pale color, decreased fecal urobilinogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Neonatal jaundice

A

Most infants develop visible jaundice due to elevation of unconjugated bilirubin concentration during their first week. This is a common condition called physiological jaundice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Contributing factors of neonatal jaundice

A
  1. Low glucronyltransferase activity in hepatocytes
    Before birth, glucuronyltransferase is actively down-regulated, since bilirubin needs to remain unconjugated in order to cross the placenta to avoid being accumulated in the fetus. After birth, it takes some time for this enzyme to gain function, leading to physiological jaundice.
  2. Shorter life span of fetal RBCs
    RBC lifespan is approximately 80 to 90 days in a full term infant, compared to 100 to 120 days in adults
  3. Lower conversion of bilirubin into urobilinogen in the intestines
    Due to intestinal flora not being established yet; results in relatively high absorption of bilirubin back into the circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Pathological neonatal jaundice

A

Extreme jaundice can cause permanent brain damage from kernicterus (bilirubin encephalopathy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Pathological neonatal jaundice critical lab values

A

Bilirubin > 15 mg/dL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Treatment for neonatal jaundice

A

Phototherapy

Plasma exchange transfusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Dubin-johnson syndrome

A

Rare autosomal disorder that is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Dubin-johnson syndrome lab findings

A

Increase in conjugated bilirubin without elevation of ALT or AST

Patient typically does not have symptoms and does not require treatment.

28
Q

Rotor syndrome

A

Rare, relatively benign autosomal recessive bilirubin disorder. Defect in hepatic storage of conjugated bilirubin, which leaks into the plasma, resulting in hyperbilirubinemia

29
Q

Rotor syndrome lab findings

A

Characterized by chronic conjugated and unconjugated hyperbilirubinemia without evidence of hemolysis

30
Q

Gilbert’s syndrome

A

Relatively common. Reduced activity of the enzyme glucuronyltransferase, which conjugates bilirubin (~30% of normal activity). Normally no serious consequences but can have mild jaundice.

31
Q

Gilbert’s syndrome labs

A

Produces mildly elevated levels of unconjugated bilirubin (<3 mg/dL)

32
Q

Crigler-Najjar syndrome

A

Very rare inherited disorder affecting the metabolism of bilirubin. Minimal (Type II) to absent (Type I) activity of the enzyme glucuronyltransferase, which conjugates bilirubin.

Typically have jaundice and very high levels of unconjugated bilirubin which can lead to kernicterus.

33
Q

Crigler-najjar syndrome lab findings

A

Unconjugated hyperbilirubinemia in the presence of normal liver function test findings is characteristic

34
Q

Elevated indirect bilirubin ddx

A 
Neonatal jaundice
Hemolytic anemias
Trauma in the presence of a large hematoma (hemolysis)
Hemorrhagic pulmonary infarcts
Crigler-Najjar syndrome
Gilbert’s syndrome
35
Q

Elevated conjugated (direct) bilirubin ddx

A

Choledocholithiasis (gallstone in the common bile duct)
Dubin-Johnson syndrome
Cancer of the head of the pancreas

36
Q

Bilirubin interfering factors

A 
1. Patient diet and medications:
High fat meal may cause decreased bilirubin by interfering with the chemical reactions. 
Certain foods (carrots, yams) and drugs (pyridium-urine) can increase the yellow hue in the serum and falsely increase bilirubin levels. 
Prolonged fasting and anorexia raise the bilirubin level
Nicotinic acid (hyperlipidemia tx) increases unconjugated bilirubin.
  1. Specimen care:
    Light: 1-hr exposure of the specimen to sunlight or high-intensity artificial light at room temperature will decrease the bilirubin content
    Air bubbles and shaking of the specimen may cause decreased levels
37
Q

Bilirubin levels in which there is detectable jaundice

A

> 2.5 to 3 mg/dL in adults

> 5 mg/dL in newborn

38
Q

Alkaline phosphatase (ALP)

A

An enzyme originating mainly in the bone, liver, biliary tract epithelium, and placenta, with some activity in the kidney and intestines.
It is used as an index of liver and bone disease when correlated with other clinical findings.

39
Q

ALP: Liver disease

A

When excretion of this enzyme is impaired as a result of obstruction in the biliary tract
During rapid regeneration of biliary tract after injury (contents of cells spill out during cell division).

40
Q

ALP: bone disease

A

The enzyme level rises in proportion to new bone cell production resulting from osteoblastic activity and the deposit of calcium in the bones

41
Q

ALP is the most sensitive test to indicate

A

Tumor metastasis to the liver

Also concerning of possible bone metastasis.

42
Q

Sources of ALP from bone origin:

A

Pathologic new bone growth occurs with osteoblastic metastatic tumors (e.g. breast, prostate)
Paget’s disease (excessive breakdown and formation of bone, followed by disorganized bone remodeling)
Healing fractures
RA
Hyperparathyroidism
Normal growing bones

43
Q

ALP 1

A

Isoenzyme of liver origin

44
Q

ALP 2

A

Isoenzyme of bone origin

45
Q

ALP 3

A

Isoenzyme elevated in intestinal pathology

46
Q

ALP and 5’-nucleotidase

A

If both are elevated the most likely source is liver

47
Q

ALP and GGT

A

If both are elevated once again the likely source is the liver

48
Q

Bone disease with elevated ALP ddx

A

Paget’s disease (levels 10 to 25x normal)
Metastatic bone tumor
Osteogenic sarcoma
Osteomalacia

49
Q

Possible causes of decreased ALP

A 
Congenital hypophosphatemia
Malnutrition, scurvy (vitamin C deficiency)
Hypothyroidism
Pernicious anemia
Celiac sprue
50
Q

ALP interfering factors

A
  1. Patient population: Young children, those experiencing rapid growth, pregnant women, postmenopausal women have physiologically high levels of ALP.
  2. Diet: Recent ingestion of a meal (esp. fatty meal) may cause elevation, so a fasting patient is preferred
    Overnight fasting for isoenzymes.
  3. Specimen care: Testing should be done the same day and sample should be refrigerated (as ALP levels increase at room temp)
    ALP levels decrease if blood is anticoagulated (i.e. with warfarin)
  4. Medications (examples slide 46)
51
Q

Aminotransferases

A

Enzymes that catalyze the reversible transfer of an amino group between an amino acid and an alpha-keto acid. Needed to synthesize liver proteins.

Includes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

52
Q

Alanine aminotransferase (ALT)

A

An enzyme with high concentrations found in the liver and relatively low concentrations found in the heart, muscle, and kidney (it is pretty much liver-specific).

Used to identify hepatocellular diseases of the liver.

53
Q

Significantly elevated ALT ddx

A

Hepatitis
Hepatic necrosis or ischemia
Viral, infectious, or toxic hepatitis (30 to 50x normal)

54
Q

Moderately elevated ALT ddx

A 
Cirrhosis
Cholestasis
Hepatic tumor
Hepatotoxic drugs
Obstructive jaundice
Severe burns
Trauma to striated muscle
55
Q

Mildly increased ALT ddx

A

Pancreatitis
Myocardial infarction (with liver damage)
Infectious mononucleosis
Shock (Injury or disease affecting the liver, heart, or skeletal muscles will cause a release of this enzyme into the bloodstream.)

56
Q

ALT interfering factors

A
  1. Medications: Salicylates (ASA) may alter ALT levels (either increased or decreased)
    Drugs that increase levels - acetaminophen, allopurinol, codeine, indomethacin, INH (isoniazid), methotrexate, methyldopa, nitrofurantoin, OCPs, propranolol, tetracyclines and verapamil. Heparin causes increased ALT.
  2. Patient population:
    Obesity causes increases in ALT.
  3. Specimen care:
    Hemolyzed blood causes increases in ALT
57
Q

Aspartate aminotransferase (AST)

A

An enzyme present in tissues of high metabolic activity
Found in high concentration in heart muscle, liver cells, skeletal muscle cells, and to a lesser degree in the kidneys, brain, pancreas, spleen (RBCs) and lungs (not liver-specific).

Amount of AST in the blood is directly related to the number of damaged cells and the amount of time that passes between injury to the tissue and the test.

58
Q

AST and AMI

A

In AMI, the AST level rises within 6 to 10 hours after an MI, peaks at 12 to 48 hours, and returns to normal in 3 to 4 days assuming further cardiac injury does not occur.

If there is a second rise in AST levels then it could indicate extension from initial injury.

59
Q

Significantly elevated AST ddx

A

Acute myocardial infarction (AMI) (4 to 10x normal value)

Liver disease (10 to 100x normal)
Acute and chronic hepatitis 
Active cirrhosis (drug or alcohol induced)
Alcoholic hepatitis
Infectious mononucleosis
Hepatic necrosis and metastasis
Reye’s syndrome (potentially fatal syndrome that has numerous detrimental effects on many organs, especially the brain and liver; associated with aspirin use in children)
Primary or metastatic carcinoma

**Notice that it is MUCH more elevated in liver disease!

60
Q

Decreased AST ddx

A

Chronic renal dialysis
Acute renal disease
Vitamin B₆ deficiency (B6 is a required cofactor for AST activity)

61
Q

AST interfering factors

A
  1. Patient population: Slight decreases occur in pregnancy, when there is abnormal metabolism of pyridoxine (vitamin B₆).
  2. Alcohol/medications:
    Alcohol ingestion affects results
    Hepatotoxic medications
  3. Concurrent pathologies:
    False decreases occur in DKA, azotemia, and severe liver disease. Gross hemolysis can cause falsely elevated level.
62
Q

AST vs ALT level comparison: AMI

A

AST level is always increased in AMI, but ALT does not always increase in AMI unless there is liver damage.

63
Q

AST vs ALT: Acute Liver

A

Usually ALT>AST, while in chronic liver conditions, AST>ALT.

acute toxic or viral hepatitis: ALT&raquo_space;> AST
hepatic necrosis or ischemia: ALT>AST
extrahepatic biliary obstruction: ALT>AST

64
Q

AST vs ALT: Chronic liver

A

Intrahepatic biliary obstruction: AST>ALT

alcoholic liver disease: AST > ALT

65
Q

Gamma Glutamyl transpeptidase (GGT)

A

Present mainly in the liver, biliary tract, kidney, and pancreas. Used to determine hepatobiliary dysfunction/liver cell dysfunction and to detect alcohol-induced liver disease

Very sensitive to the amount of alcohol consumed by chronic alcoholics.

66
Q

Increased levels of GGT ddx

A

Liver disease (hepatitis, cirrhosis, hepatic necrosis, hepatic tumor or metastasis, hepatotoxic drugs, cholestasis, jaundice)

Myocardial infarction (may occur 4 days after AMI, probably implies liver damage from cardiac insufficiency)

Alcohol ingestion

Pancreatic diseases (pancreatitis, cancer)

Carcinoma of the prostate

EBV, CMV and Reye’s syndrome (may be associated with subclinical hepatitis that can occur with these infections)

67
Q

GGT interfering factors

A
  1. Patient population: may be decreased late in pregnancy
  2. Drugs: Alcohol, phenytoin, and phenobarbital cause increased levels. Clofibrate (hyperlipidemia treatment) and OCPs may cause decreased levels

Lab Med II (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions